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Sulfasalazine pinpointed as reason for high triple-therapy discontinuation
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Adverse events related to sulfasalazine played a role in the higher discontinuation rate observed for rheumatoid arthritis (RA) patients on triple therapy when compared with similar patients taking methotrexate and a tumor necrosis factor inhibitor in an observational cohort study of historical data during 2006-2012.
The findings shed some light on understanding if the noninferior efficacy of triple therapy (TT) with methotrexate (MTX), sulfasalazine (SSZ), and hydroxychloroquine (HCQ) in randomized trials versus combination MTX plus tumor necrosis factor inhibitor (MTX-TNFi) is matched by patients’ persistence and adherence to TT in real-world data.
“With the proven efficacy of these combination therapies, an understanding of the real-world observations outside of clinical trials should be investigated to determine if similar experiences are seen in clinical practice as in clinical trials,” first author Daniel P. Erhardt, MD, MPH, of the George E. Wahlen VA Medical Center, Salt Lake City, and his colleagues wrote in Arthritis Care & Research.
In the current study, the research team identified veterans with RA escalating treatment from MTX to MTX-TNFi (n = 2,125) or to triple therapy (n = 171) from Veterans Affairs (VA) clinical and administrative databases during 2006-2012.
Patients taking MTX-TNFi consistently had significantly higher levels of persistence than did TT patients regardless of the strictness of the definition used. The highest level of persistence as defined in the study – all medications (including MTX) filled without a 90-day or longer gap in treatment over the 12-month study period – was observed in 43.2% of the MTX-TNFi arm, compared with 17.6% in the TT arm. A more liberal definition of persistence that allowed discontinuation of any one disease-modifying antirheumatic drug (DMARD) in TT or MTX in the MTX-TNFi group – provided no new DMARDs were initiated – yielded a persistence rate of 50.3% for MTX-TNFi vs. 32.8% for the TT arm. The persistence rate for MTX-TNFi worsened somewhat to 42.9% when the same discontinuation was allowed and switching was permitted between drugs within the TNFi class for the MTX-TNFi combination group, but it stayed lower for the TT group at 33.9% when single DMARD discontinuation was allowed and switching between nonbiologic DMARDs was permitted (without a 90-day or longer gap prior to the switch).
Adherence as defined by 80% or more of days covered at 1 year was 25.3% in the MTX-TNFi arm, with individual adherence rates of 44.3% for MTX and 46% for TNFi. In comparison, adherence for TT overall was 10.5%, with adherence rates of 48.6% for MTX, 32.8% for HCQ, and 18.7% for SSZ.
TT group patients most commonly discontinued sulfasalazine (20.9%), followed by MTX (8.7%) and HCQ (7.8%), whereas in those treated with MTX-TNFi, many more stopped TNFi alone (53.9%) than MTX alone (19.1%). It also was more common to stop SSZ and HCQ together (37.4%) or all TT drugs (23.5%) than it was to stop MTX plus HCQ together (1.7%).
The most common reason for discontinuation in both groups was an adverse drug event (ADE), cited as the reason in 43.5% of TT patients and 35.7% of combination-therapy patients. Most SSZ discontinuations were reported as an ADE, most often because of concerns of GI toxicity or symptoms, the researchers said. GI toxicity or symptoms was cited as a reason for discontinuing for 18.3% of TT patients who discontinued, compared with only 1.7% of MTX-TNFi patients.
“Findings from our study indicate that ADE play a significant role in influencing drug discontinuation, and further efforts should focus on ways to mitigate ADE when initiating or escalating drug regimens for RA,” they concluded.
They noted that a large percentage of subjects who discontinued their combination therapy for RA were lost to follow-up from the VA system: 34.8% in the TT group and 32.2% in the MTX-TNFi group.
“Research should continue to focus on ascertaining methods to improve real-world treatment retention rates,” they advised.
“More research is also warranted to determine whether patient factors that influence medication adherence independently affect the likelihood of achieving clinical remission, regardless of which therapy is chosen for the treatment of their RA,” they added.
The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported receiving research funding and grants from several pharmaceutical companies.
SOURCE: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Compared with RA patients on methotrexate and a TNF inhibitor, patients on triple therapy are more likely to discontinue treatment, largely because of adverse events with sulfasalazine (SSZ).
Major finding: Adherence was higher for the MTX-TNFi group (26%) than for the triple-therapy group (11%) (P less than .0001). The triple-therapy group was associated with significantly more treatment discontinuation, which was most often because of the adverse drug events from SSZ.
Study details: A retrospective observational cohort study using historical data from Veterans Affairs clinical and administrative databases during Jan. 1, 2006–Dec. 31, 2012.
Disclosures: The research was supported by Specialty Care Center of Innovation in the Veterans Health Administration and by the Health Services Research and Development division of the Department of Veterans Affairs. Several of the authors reported having received research funding and grants from several pharmaceutical companies.
Source: Erhardt DP et al. Arthritis Care Res. 2018 Sep 17. doi: 10.1002/acr.23759
Pregnancy registries are a valuable resource
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of the human pregnancy experience. However, although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of these registries are their prospective nature (enrolled before the outcome is known) and enrollment over a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions). Registries can identify early signals of teratogenicity, but they have several limitations: selection bias that results from voluntary reporting; target populations that are not representative; lost-to-follow-up pregnancies that may have had different outcomes than those with documented outcomes; elective terminations and fetal deaths without birth defects and spontaneous abortions, all of which may lack details; the lack of control groups (with some exceptions); and the publication of results that may be delayed or not be in a peer-reviewed journal. Because the total number of exposed pregnancies is unknown, the data cannot be used to calculate prevalences, but they can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports (reported after outcome is known). Such reports are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. But they may be helpful in detecting unusual patterns of birth defects.
For the following drugs, web addresses can be obtained from the Food and Drug Administration website, List of Pregnancy Exposure Registries.
MotherToBaby
A large registry, the MotherToBaby Organization of Teratology Information Specialists (OTIS) (877-311-8972), involves patients in several different categories and the effects of the drugs on the embryo-fetus: autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma at less than 20 weeks’ gestation; vaccines; and heterozygous or homozygous familial hypercholesterolemia.
For the autoimmune diseases, the drugs and trade names are abatacept (Orencia), adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade), leflunomide (Arava), otezla (Apremilast), teriflunomide (Aubagio), tocilizumab (Actemra), tofacitinib (Xeljanz), and ustekinumab (Stelara).
For the asthma group, the drug being investigated is mepolizumab (Nucala).
Two vaccines – for tetanus, diphtheria, and pertussis (Tdap) and meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menveo) – are being studied.
The last category is heterozygous or homozygous familial hypercholesterolemia. The two agents in this category are alirocumab (Praluent) and evolocumab (Repatha).
Other registries
Breast cancer
The Mother Pregnancy Registry, INC Research (800-690-6720), is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), or trastuzumab (Herceptin).
Epilepsy
The Antiepileptic Drug Pregnancy registry (888-233-2334) is studying eslicarbazepine (Aptiom) and pregabalin (Lyrica).
Fabry disease
The Fabry Registry, Genzyme Corp (617-591-5500) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Hepatitis B
The Ribavirin Pregnancy Registry, INC Research (800-593-2214) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Hypercholesterolemia
Lomitapide (Juxtapid) is being studied by the Global Lomitapide Pregnancy Exposure Registry managed by Aegerion (877-902-4099). The drug is used for homozygous familial hypercholesterolemia.
Mucopolysaccharidosis
The Mucopolysaccharidosis I (MPS I) registry, Genzyme (617-591-5500) is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI), clinical surveillance program (BioMarin Pharmaceutical) (415-506-6849 or 415-506-6703).
Multiple sclerosis
Novartis is conducting the Gilenya Pregnancy Registry (877-598-7237) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Alemtuzumab (Lemtrada), also indicated for multiple sclerosis, is the target agent for the LEMTRADA Pregnancy Exposure Registry (866-758-2990).
Narcolepsy and other sleep disorders
Armodafinil (Nuvigil), used for excessive sleepiness associated with narcolepsy and other sleep disorders, is being studied in the Nuvigil Pregnancy Registry (866-404-4106). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Others
Two Merck pregnancy registries (800-986-8999) cover the following conditions: type 2 diabetes sitagliptin+metformin (Janumet) or sitagliptin (Januvia); and migraine headaches rizatriptan (Maxalt).
GlaxoSmithKline is conducting two registries: the Belimumab Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (Benlysta) (877-681-6296); and Promacta Pregnancy Registry for women treated for thrombocytopenia with eltrombopag (Promacta) (888-825-5249).
Psychiatric Drugs
The National Pregnancy Registry for Atypical Antipsychotics (866-961-2388) is studying 10 drugs: aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon).
The National Pregnancy Registry for Antidepressants (844-405-6185) is studying amitriptyline (Elavil), amoxapine (Asendin), bupropion (Forfivo XL and Wellbutrin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), desvenlafaxine (Prisiq), doxepin (Sinequan), escitalopram (Lexapro), fluvoxamine (Luvox), fluoxetine (Prozac), imipramine (Tofranil), isocarboxazid (Marplan), levomilnacipran (Fetzima), maprotiline (Ludiomil), mirtazapine (Remeron), nefazodone (Serzone), nortriptyline (Pamelor), paroxetine (Paxil), phenelzine (Nardill), protriptyline (Vivactil), selegiline (Emsam), sertraline (Zoloft), tranylcypromine (Pamate), trazodone (Desyrel), trimipramine (Surmontil), venlafaxine (Effexor), and vilazodone (Viibryd).
The National Pregnancy Registry of Psychostimulants (866-961-2388) is studying amphetamine (Adderall), dextroamphetamine (Dexedrine and Focalin), lisdexamfetamine (Vyvanse), methylphenidate (Concerta, Daytrana, Desoxyn, Ritalin), and modafinil (Provigil).
The antidepressant duloxetine (Cymbalta) is being studied by the Cymbalta Pregnancy Registry (866-814-6975).
Transplant patients
Renal transplant patients exposed to mycophenolate (CellCept) can be enrolled in the Transplantation Pregnancy Registry International (877-955-6877) or the Mycophenolate Pregnancy Registry (800-617-8191). The Transplantation Pregnancy Registry International also is enrolling renal transplant patients exposed to belatacept (Nulojix).
Vaccines
A quadrivalent influenza vaccine (Afluria) is being studied by the Seqirus Influenza Vaccine Pregnancy Registry (855-358-8972). A second vaccine for meningococcal disease meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 (Menactra) is under study by the Menactra Vaccine Pregnancy Registry (800-822-2463). The Bexsero Pregnancy Registry (877-413-4759) is open to patients who have received the meningococcal group B vaccine (Bexsero). The Hepatitis B Vaccine [Recombinant] Adjuvanted Pregnancy Registry, also listed as HEPLISAV-B, is enrolling patients who have received that vaccine (844-443-7734); it is supported by the Dynavax Technologies Corporation.
Because the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Arthritis prevalent in older adults with any degree of depression
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
Arthritis is highly prevalent in older adults with any degree of depression, results of a recent study suggest.
Doctor-diagnosed arthritis was reported by more than 50% of older adults with mild depression, according to results of the study, which was based on data from the National Health and Nutrition Examination Survey (NHANES).
The prevalence of arthritis exceeded 60% in participants with moderate depression, and approached 70% for those with severe depression, according to the study, published in the International Journal of Geriatric Psychiatry.
Based on those findings, arthritis and depression need to be viewed as frequently co-occurring physical and psychosocial issues, reported Jessica M. Brooks, PhD, of the department of psychiatry at Dartmouth College, Lebanon, N.H., and her coauthors.
“It may be critical for mental health care providers to provide regular arthritis-related pain assessments and evidence‐based treatments for co‐occurring arthritis in older adults with or at risk for depression,” Dr. Brooks and her colleagues said in their report.
Their analysis was based on 2,483 women and 2,309 men aged 50 years and older (mean age, 64.5 years) who had participated in the NHANES survey between 2011 and 2014. Out of that sample, 2,094 participants (43.7%) said they had been told by a doctor that they had arthritis, the researchers said.
The rate of arthritis was 38.2% for participants with no depressive symptoms as indicated by a 0-4 score on the 9-item Patient Health Questionnaire (PHQ-9). By comparison, rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression by PHQ-9.
Individuals with arthritis had a significantly higher mean PHQ-9 score, at 4.6, compared with 2.6 for those without arthritis (P less than .001), the investigators said.
that controlled for age, gender, comorbid conditions, and other factors such as smoking history.
Establishing prevalence rates of arthritis in older adults with depression is an “important step” toward informing mental health professionals on the need to identify and treat arthritis-related pain, Dr. Brooks and her coauthors said.
“Addressing arthritis in mental health treatment and behavioral medicine may also help to reduce the overlapping cognitive, behavioral, and somatic symptoms in older adults with depressive symptoms and arthritis, which may be difficult for providers to disentangle through brief screening procedures and treat through conventional depression care,” they wrote.
The investigators cited several limitations. For example, the cross-sectional nature of the study makes it difficult to draw conclusions about causality. In addition, Dr. Brooks and her colleagues did not distinguish between different types of arthritis.
The researchers declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
SOURCE: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1022/gps.4971.
FROM THE INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
Key clinical point: “It may be critical for mental health care providers to provide regular arthritis-related pain assessments” for older adults with or at risk for depression.
Major finding: Rates of arthritis were 55.0%, 62.9%, and 67.8% for those with mild, moderate, or severe depression, respectively, according to the 9-item Patient Health Questionnaire-9 scores.
Study details: Findings on 2,483 women and 2,309 men aged 50 years and older who participated in the National Health and Nutrition Examination Survey.
Disclosures: Dr. Brooks and her coauthors declared no conflicts of interest. The study was supported by several U.S. institutes, including the National Institute of Mental Health, and by numerous entities related to Dartmouth, including the Dartmouth Health Promotion and Disease Prevention Research Center. The Howard and Phyllis Schwartz Philanthropic Fund also provided funding.
Source: Brooks JM et al. Int J Geriatr Psychiatry. 2018 Sep 19. doi: 10.1002/gps.4971.
Patient outcome questionnaires take a beating in talk
LAS VEGAS – The purpose of patient-reported outcome data is to help physicians understand how patients are faring so they can make better clinical decisions. But commonly used assessments in rheumatoid arthritis aren’t doing their job, rheumatologist Clifton O. Bingham III, MD, said at the annual Perspectives in Rheumatic Diseases.
“We’re really missing the boat in terms of all these things that are important to our patients with rheumatoid arthritis,” said Dr. Bingham of Johns Hopkins Arthritis Center, Baltimore. For example, multiple instruments used in RA ignore important topics such as pain assessment, fatigue, and physical function, he explained at the conference, held by Global Academy for Medical Education.
There’s good news, however. “Can we come up with something that can overcome these barriers?” he asked. “Yes we can.”
First, Dr. Bingham described the weaknesses of patient questionnaires. “Just because an instrument has been used before, like the SF-36, doesn’t necessarily mean that it is measuring what it’s supposed to be measuring or that the information it gathers is important,” he said.
Even instruments that ask about issues important to RA patients can fail to produce a full picture. As Dr. Bingham noted, the Multidimensional Health Assessment Questionnaire (MD-HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI) instruments do ask about joint stiffness, but they’re only interested in whether patients felt stiff in the morning and how long the stiffness lasted.
In fact, Dr. Bingham said, a 2013 study found that 23% of 288 patients with RA reported having stiffness only in the morning; most had it all day and night or in the morning and evening (Young KO, et al. ACR 2013, Abstract 2273).
Dr. Bingham listed other problems with patient-reported outcome instruments, such as a question on the MD-HAQ about “fatigue or tiredness.” He said patients actually distinguish between the two: “Patients say they’re tired when they don’t get a good night’s sleep, but that’s not the same as fatigue from RA.”
Is there a better way? Dr. Bingham has explored this issue while serving on the executive committee of Outcome Measures in Rheumatology, an international group supported by drugmakers and other entities. (The funding is arms-length, and he is not compensated.)
Dr. Bingham supports the use of the recently developed Patient-Reported Outcome Measurement Information System (PROMIS), which was established by the National Institutes of Health.
“It lets us see how our patients are doing in their real lives and gives us information about their disease in terms of their activity,” Dr. Bingham said.
He pointed to the upcoming results of a survey of patients with RA that found a wide majority of patients believed many questions on the PROMIS-29 and PROMIS short form questionnaires – regarding pain interference, fatigue and physical function – to be sufficient. However, they did want to see more questions about physical function.
A survey of doctors also revealed that PROMIS results often led them to identify new symptoms or comorbidities, and they frequently took action as a result. In some cases, the results spurred adjustments to RA treatment or medication.
“These measures have the right stuff,” Dr. Bingham said.
He suggested exploring the use of PROMIS-29 in conjunction with other assessments as needed.
“You can administer the questionnaires on tablet computers,” said Dr. Bingham, who added that styluses with built-up handles can be useful for patients with RA when they respond to the questions.
“The information comes straight into your medical record,” he said, “and it can be shown to you and your patient at the same time.”
For more about PROMIS, visit healthmeasures.net.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – The purpose of patient-reported outcome data is to help physicians understand how patients are faring so they can make better clinical decisions. But commonly used assessments in rheumatoid arthritis aren’t doing their job, rheumatologist Clifton O. Bingham III, MD, said at the annual Perspectives in Rheumatic Diseases.
“We’re really missing the boat in terms of all these things that are important to our patients with rheumatoid arthritis,” said Dr. Bingham of Johns Hopkins Arthritis Center, Baltimore. For example, multiple instruments used in RA ignore important topics such as pain assessment, fatigue, and physical function, he explained at the conference, held by Global Academy for Medical Education.
There’s good news, however. “Can we come up with something that can overcome these barriers?” he asked. “Yes we can.”
First, Dr. Bingham described the weaknesses of patient questionnaires. “Just because an instrument has been used before, like the SF-36, doesn’t necessarily mean that it is measuring what it’s supposed to be measuring or that the information it gathers is important,” he said.
Even instruments that ask about issues important to RA patients can fail to produce a full picture. As Dr. Bingham noted, the Multidimensional Health Assessment Questionnaire (MD-HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI) instruments do ask about joint stiffness, but they’re only interested in whether patients felt stiff in the morning and how long the stiffness lasted.
In fact, Dr. Bingham said, a 2013 study found that 23% of 288 patients with RA reported having stiffness only in the morning; most had it all day and night or in the morning and evening (Young KO, et al. ACR 2013, Abstract 2273).
Dr. Bingham listed other problems with patient-reported outcome instruments, such as a question on the MD-HAQ about “fatigue or tiredness.” He said patients actually distinguish between the two: “Patients say they’re tired when they don’t get a good night’s sleep, but that’s not the same as fatigue from RA.”
Is there a better way? Dr. Bingham has explored this issue while serving on the executive committee of Outcome Measures in Rheumatology, an international group supported by drugmakers and other entities. (The funding is arms-length, and he is not compensated.)
Dr. Bingham supports the use of the recently developed Patient-Reported Outcome Measurement Information System (PROMIS), which was established by the National Institutes of Health.
“It lets us see how our patients are doing in their real lives and gives us information about their disease in terms of their activity,” Dr. Bingham said.
He pointed to the upcoming results of a survey of patients with RA that found a wide majority of patients believed many questions on the PROMIS-29 and PROMIS short form questionnaires – regarding pain interference, fatigue and physical function – to be sufficient. However, they did want to see more questions about physical function.
A survey of doctors also revealed that PROMIS results often led them to identify new symptoms or comorbidities, and they frequently took action as a result. In some cases, the results spurred adjustments to RA treatment or medication.
“These measures have the right stuff,” Dr. Bingham said.
He suggested exploring the use of PROMIS-29 in conjunction with other assessments as needed.
“You can administer the questionnaires on tablet computers,” said Dr. Bingham, who added that styluses with built-up handles can be useful for patients with RA when they respond to the questions.
“The information comes straight into your medical record,” he said, “and it can be shown to you and your patient at the same time.”
For more about PROMIS, visit healthmeasures.net.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – The purpose of patient-reported outcome data is to help physicians understand how patients are faring so they can make better clinical decisions. But commonly used assessments in rheumatoid arthritis aren’t doing their job, rheumatologist Clifton O. Bingham III, MD, said at the annual Perspectives in Rheumatic Diseases.
“We’re really missing the boat in terms of all these things that are important to our patients with rheumatoid arthritis,” said Dr. Bingham of Johns Hopkins Arthritis Center, Baltimore. For example, multiple instruments used in RA ignore important topics such as pain assessment, fatigue, and physical function, he explained at the conference, held by Global Academy for Medical Education.
There’s good news, however. “Can we come up with something that can overcome these barriers?” he asked. “Yes we can.”
First, Dr. Bingham described the weaknesses of patient questionnaires. “Just because an instrument has been used before, like the SF-36, doesn’t necessarily mean that it is measuring what it’s supposed to be measuring or that the information it gathers is important,” he said.
Even instruments that ask about issues important to RA patients can fail to produce a full picture. As Dr. Bingham noted, the Multidimensional Health Assessment Questionnaire (MD-HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI) instruments do ask about joint stiffness, but they’re only interested in whether patients felt stiff in the morning and how long the stiffness lasted.
In fact, Dr. Bingham said, a 2013 study found that 23% of 288 patients with RA reported having stiffness only in the morning; most had it all day and night or in the morning and evening (Young KO, et al. ACR 2013, Abstract 2273).
Dr. Bingham listed other problems with patient-reported outcome instruments, such as a question on the MD-HAQ about “fatigue or tiredness.” He said patients actually distinguish between the two: “Patients say they’re tired when they don’t get a good night’s sleep, but that’s not the same as fatigue from RA.”
Is there a better way? Dr. Bingham has explored this issue while serving on the executive committee of Outcome Measures in Rheumatology, an international group supported by drugmakers and other entities. (The funding is arms-length, and he is not compensated.)
Dr. Bingham supports the use of the recently developed Patient-Reported Outcome Measurement Information System (PROMIS), which was established by the National Institutes of Health.
“It lets us see how our patients are doing in their real lives and gives us information about their disease in terms of their activity,” Dr. Bingham said.
He pointed to the upcoming results of a survey of patients with RA that found a wide majority of patients believed many questions on the PROMIS-29 and PROMIS short form questionnaires – regarding pain interference, fatigue and physical function – to be sufficient. However, they did want to see more questions about physical function.
A survey of doctors also revealed that PROMIS results often led them to identify new symptoms or comorbidities, and they frequently took action as a result. In some cases, the results spurred adjustments to RA treatment or medication.
“These measures have the right stuff,” Dr. Bingham said.
He suggested exploring the use of PROMIS-29 in conjunction with other assessments as needed.
“You can administer the questionnaires on tablet computers,” said Dr. Bingham, who added that styluses with built-up handles can be useful for patients with RA when they respond to the questions.
“The information comes straight into your medical record,” he said, “and it can be shown to you and your patient at the same time.”
For more about PROMIS, visit healthmeasures.net.
Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES ON RHEUMATIC DISEASES
New insight into celiac disease: What you should know
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
LAS VEGAS – Mayo Clinic gastroenterologist Joseph A. Murray, MD, has a message for rheumatologists: You might think you know celiac disease, which often mimics rheumatic disorders, but there’s a good chance you don’t.
For one, researchers have discovered only in the past few years that many people with celiac disease (CD) don’t spend their days on the toilet. “It’s really come into the fore in the past 5 years that it can present totally without any GI symptoms,” Dr. Murray said in an interview following his presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
For another, he said, CD “is much more common than we thought,” affecting 1% of whites.
This is all relevant to rheumatologists, Dr. Murray said, because celiac disease can cause rheumatic symptoms and is more likely to affect patients with certain rheumatic conditions.
In the big picture, he said during his presentation, researchers now understand that most people with CD do not suffer from diarrhea, the classic symptom associated with the disorder. A 2014 Italian study of 770 patients with CD found that just one-third had diarrhea (BMC Gastroenterol. 2014;14:194).
Instead of GI symptoms – or in addition to them – CD can cause numerous symptoms that may land patients in a rheumatologist’s office. According to Dr. Murray, these include joint pain (often without joint destruction), peripheral neuropathy, general aches and pains, and chronic fatigue.
“You could have a patient presenting with nondestructive joint problems and general fatigue who has celiac disease as a cause,” he said.
Or patients could have both CD and a rheumatic condition. Patients with lupus and Sjögren’s syndrome, for example, are at higher risk of CD, Dr. Murray said.
In addition, he said, “I will often see overlap between celiac disease and rheumatic arthritis.”
What should you do if you suspect a patient has CD? Dr. Murray suggests referring the patient to a gastroenterologist, although he cautioned physicians to keep in mind that a patient with the condition may not be able to adequately absorb oral medications.
He said it’s crucial to not direct the patient to begin a gluten-free diet. The main way to test a patient for CD is through serology prior to a gluten-free diet, he said.
There’s another hitch regarding a gluten-free diet. As he explained in his presentation, it’s often difficult to convince someone who’s already gone on a gluten-free diet to go off it so they can be challenged with gluten for weeks. In these cases, he said, patients may be afraid of the return of symptoms.
As for treatment, Dr. Murray said “patients can be dramatically improved by a gluten-free diet,” although it’s often difficult for them to tolerate. “Often they’re unhappy,” he said in his presentation. “It’s not an easy diet.”
He noted that patients may go gluten free even if it’s not clear they have to. “If the diet is nutritionally adequate,” he said, “I don’t argue with success.”
Dr. Murray disclosed consulting for various drug makers, receiving royalties from Torax, and receiving grant/contracted research support from drug makers, the Broad Medical Research Program at Crohn’s & Colitis Foundation, and Oberkotter Foundation.
Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM THE ANNUAL PERSPECTIVES IN RHEUMATIC DISEASES
Predictors for worse outcomes in low–disease activity RA remain tough to come by
Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.
First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.
The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.
Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.
Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.
For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).
Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.
The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.
“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.
“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.
“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.
They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.
“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.
The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.
SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.
Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.
First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.
The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.
Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.
Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.
For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).
Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.
The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.
“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.
“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.
“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.
They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.
“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.
The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.
SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.
Disease flares are common but are hard to predict in people with rheumatoid arthritis who achieve low disease activity (LDA), and these flares are “undeniably” associated with worse disease activity, quality of life, and radiographic progression, researchers report in an analysis of a prospectively observed cohort.
First author Katie Bechman, MBChB, of the academic rheumatology department at King’s College London, and her colleagues reported online in the Journal of Rheumatology that nearly one-third of patients with RA in stable LDA states, including remission, had flares during a year of follow-up in the observational prospective REMIRA study, similar to previous reports in cohort studies.
The cohort of 152 patients had 28-joint Disease Activity Scores (DAS28) less than 3.2 for at least 1 month apart, and 66% (n = 97) of the cohort fulfilled DAS28 remission criteria (DAS28 less than 2.6). The authors defined disease flare as a DAS28 increase of more than 1.2, compared with baseline, or a DAS28 increase of more than 0.6, compared with baseline, and concurrent DAS28 of 3.2 or greater. A total of 69 (35%) were taking disease-modifying antirheumatic drug monotherapy.
Nearly one-third of RA patients (30%, n = 46) with LDA states experienced a flare during 12 months of follow-up. When limiting the cohort to patients who were in remission at baseline, 25% (n = 24) had at least one flare.
Patients who had a flare experienced significantly worse clinical outcomes at 12 months than did patients in sustained remission, reflected by higher disease activity, worse functional outcomes, and higher radiographic progression scores.
For example, patients who flared had more than a threefold greater risk for erosive progression, defined as new or larger erosions over 1 year on radiographs (hazard ratio, 3.6; 95% confidence interval, 2.77-4.67; P less than .01).
Patients’ baseline values on the Health Assessment Questionnaire-Disability Index – a measure of functional activity that is reflected by difficulties in activities of daily living – proved to be a significant independent predictor of flare (HR, 1.76; 95% CI, 1.05-2.93; P = .03) in multivariate analyses.
The researchers also found that serum biomarkers were modestly correlated with DAS28 at the time of flare. DAS28 and its components significantly correlated with multibiomarker disease activity score and calprotectin at time of flare, but correlation coefficients were low at 0.52 and 0.49, respectively. Two-thirds of flares were not associated with a rise in biomarkers.
“This might be because a flare is defined by worsening of the DAS28 composite score, and an increase in [tender joint count] and [patient’s global assessment] alone may increase the DAS28 score to a sufficient level to define a flare,” the investigators suggested.
“It is possible that a flare event is not solely the result of direct synovial inflammation but may be driven by other pathways, for example chronification of pain due to central sensitization and abnormal regulatory mechanisms. This heterogeneity may partly explain why identifying predictors of flare is challenging,” they said.
“In our study, we have shown that the occurrence of a flare is hard to predict, but undeniably associated with worse clinical outcomes at 12 months,” the researchers concluded.
They suggested that it was possible that two “distinct subtypes” of flare might exist: an “inflammatory” flare that was predominantly driven by an increase in swollen joint count and erythrocyte sedimentation rate, and a “noninflammatory” flare with a disproportionately elevated tender joint count and a high patient global assessment score.
“Differentiating these two flare types may identify potential predictors. Further research is needed to determine whether distinct flares exist and to categorize the potential predictors of each,” they added.
The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.
SOURCE: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.
FROM THE JOURNAL OF RHEUMATOLOGY
Key clinical point: Flares occur frequently in RA patients with low disease activity and are associated with worse disease activity, quality of life, and radiographic progression.
Major finding:
Study details: A study of 152 RA patients taking part in the observational prospective REMIRA study who had a stable 28-joint Disease Activity Score (DAS28) less than 3.2.
Disclosures: The research was partly funded by the U.K. National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.
Source: Bechman K et al. J Rheumatol. 2018 Sep 1. doi: 10.3899/jrheum.171375.
Difficult-to-treat RA remains difficult to define
Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.
Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.
The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.
The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.
A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.
Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.
“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.
The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.
The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.
SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.
Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.
Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.
The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.
The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.
A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.
Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.
“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.
The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.
The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.
SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.
Active disease, failure of disease-modifying antirheumatic drug therapy, and an inability to taper glucocorticoid treatment are the main characteristics of difficult-to-treat RA, according to results of a survey of mostly European rheumatologists that also revealed a wide variation in views on the factors that contribute to the concept.
Some of the issues that survey respondents considered clinically relevant in difficult-to-treat RA are not covered by current EULAR management recommendations, Nadia M.T. Roodenrijs, of University Medical Center Utrecht, the Netherlands, and her colleagues noted in a study published online in Annals of the Rheumatic Diseases.
The investigators set out to determine what a range of rheumatologists from different countries considered to be the key characteristics of difficult-to-treat RA, which has an estimated prevalence of 5%-20%, depending on the criteria used. They also sought to identify the issues relating to work-up and management that were not covered by the current EULAR recommendations.
The online survey contained four multiple choice questions that asked about the necessity of incorporating disease activity level, fatigue, number of disease-modifying antirheumatic drugs (DMARDs) that failed, and the inability to taper glucocorticoids into the concept of difficult-to-treat RA. The survey also asked three open questions seeking additional clinically relevant views on difficult-to-treat RA.
A total of 410 respondents from 33 countries (96% European) completed the survey, which was sent to rheumatologists through the Emerging EULAR Network. Overall, half of the respondents selected “disease activity score assessing 28 joints using erythrocyte sedimentation rate [DAS28-ESR] greater than 3.2 or the presence of signs suggestive of active inflammatory disease activity with a DAS28-ESR of 3.2 or less” as characteristics of difficult-to-treat RA. About 42% of respondents included fatigue as a characteristic and 48% selected failure to two or more conventional DMARDs and two or more biological/targeted synthetic DMARDs. Furthermore, 89% of respondents identified the inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily to be a characteristic of difficult-to-treat RA.
Other clinically important issues identified by the respondents as currently missing from EULAR management recommendations included interfering comorbidities, especially cardiovascular disease, infection, and malignancy; extra-articular manifestations; and polypharmacy.
“The results of this survey underscore the difficulty in establishing an unambiguous concept of difficult-to-treat RA, which is seen as a heterogeneous condition not fully covered by EULAR recommendations,” the authors wrote.
The authors noted that their findings would help fuel discussion on the issues to include in the management recommendations for difficult-to-treat RA currently under consideration by a recently established EULAR task force.
The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.
SOURCE: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point: There is wide variation in the views of rheumatologists across Europe on the key characteristics of difficult-to-treat RA. Some issues that rheumatologists consider to be clinically relevant are not covered by current EULAR recommendations.
Major finding:
Study details: An online survey completed by 410 rheumatologists from 33 countries.
Disclosures: The study was not funded with a specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Some of the authors reported receiving fees from several pharmaceutical countries.
Source: Roodenrijs NMT et al. Ann Rheum Dis. 2018 Sep 7. doi: 10.1136/annrheumdis-2018-213687.
Infliximab biosimilar only moderately less expensive in Medicare Part D
The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.
Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.
However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.
Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.
Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.
While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.
That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.
In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.
“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.
To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.
Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.
The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.
However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.
For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.
Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.
“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.
The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.
The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.
Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.
However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.
Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.
Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.
While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.
That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.
In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.
“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.
To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.
Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.
The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.
However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.
For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.
Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.
“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.
The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.
The infliximab-dyyb biosimilar was only moderately less expensive than the originator infliximab product Remicade in the United States in 2017 under Medicare Part D, an analysis shows.
Infliximab-dyyb (Inflectra) cost 18% less than infliximab, with an annual cost exceeding $14,000 in an analysis published online Sept. 4 in JAMA by Jinoos Yazdany, MD, of the division of rheumatology at the University of California, San Francisco, and her coauthors.
However, “without biosimilar gap discounts in 2017, beneficiaries would have paid more than $5,100 for infliximab-dyyb, or nearly $1,700 more in projected out-of-pocket costs than infliximab,” Dr. Yazdany and her coauthors wrote.
Biologics represent only 2% of U.S. prescriptions but made up 38% of drug spending in 2015 and accounted for 70% of growth in drug spending from 2010 to 2015, according to Dr. Yazdany and her colleagues.
Biologics for rheumatoid arthritis (RA) cost more than $14,000 per year, and in 2015, 3 were among the top 15 drugs in terms of Medicare expenditures, they added.
While biosimilars are supposed to increase competition and lower prices, it’s an open question whether they actually reduce out-of-pocket expenditures for the 43 million individuals with drug benefits under Medicare Part D.
That uncertainty is due in part to the complex cost-sharing design of Part D, which includes an initial deductible, a coverage phase, a coverage gap, and catastrophic coverage.
In 2017, the plan included an initial $400 deductible, followed by the coverage phase, in which the patient paid 25% of drug costs. In the coverage gap, which started at $3,700 in total drug costs, the patient’s share of drug costs increased to 40% for biologics, and 51% for biosimilars. In the catastrophic coverage phase, triggered when out-of-pocket costs exceeded $4,950, the patient was responsible for 5% of drug costs.
“Currently, beneficiaries receive a 50% manufacturer discount during the gap for brand-name drugs and biologics, but not for biosimilars,” Dr. Yazdany and her coauthors said in the report.
To evaluate cost-sharing for infliximab-dyyb, which in 2016 became the first available RA biosimilar, the authors analyzed data for all Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.
Out of 2,547 plans, only 10% covered the biosimilar, while 96% covered infliximab, the authors found.
The mean total cost of infliximab-dyyb was “modestly lower,” they reported. Eight-week prescription costs were $2,185 for infliximab-dyyb versus $2,667 for infliximab, while annual costs were $14,202 for the biosimilar and $17,335 for infliximab.
However, all plans required coinsurance cost-sharing for the biosimilar, they said. The mean coinsurance rate was 26.6% of the total drug cost for the biosimilar and 28.4% for infliximab.
For beneficiaries, projected annual out-of-pocket costs without the gap discount were $5,118 for infliximab-dyyb and $3,432 for infliximab, the researchers said.
Biosimilar gap discounts are set to start in 2019, according to the authors. However, they said those discounts may not substantially reduce out-of-pocket costs for Part D beneficiaries because of the high price of infliximab-dyyb and a coinsurance cost-sharing rate similar to that of infliximab.
“Further policies are needed to address affordability and access to specialty drugs,” Dr. Yazdany and her coauthors concluded.
The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. Dr. Yazdany reported receiving an independent investigator award from Pfizer. Her coauthors reported no conflict of interest disclosures.
FROM JAMA
Key clinical point:
Major finding: Infliximab-dyyb was 18% less costly than infliximab, with an annual cost exceeding $14,000.
Study details: Analysis of data for 2,547 Part D plans in the June 2017 Medicare Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files.
Disclosures: The study was funded in part by grants from the Agency for Healthcare Research and Quality, the Robert L. Kroc Endowed Chair in Rheumatic and Connective Tissue Diseases, and other sources. One author reported receiving an independent investigator award from Pfizer.
Source: Yazdany J et al. JAMA. 2018;320(9):931-3.
Diclofenac’s cardiovascular risk confirmed in novel Nordic study
Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE) compared with individuals who didn’t initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4-1.7).
The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with those starting ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1-1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE compared with initiating naproxen (95% CI, 1.1-1.5).
“Diclofenac is the most frequently used NSAID in low-, middle-, and high-income countries and is available over the counter in most countries; therefore, its cardiovascular risk profile is of major clinical and public health importance,” wrote Dr. Schmidt and his coauthors.
In all, the study included 1,370,832 individuals who initiated diclofenac, 3,878,454 ibuprofen initiators, 291,490 naproxen initiators, and 764,781 acetaminophen initiators. Those starting diclofenac were compared with those starting other medications, and with 1,303,209 individuals who sought health care but did not start one of the medications.
The researchers used the longstanding and complete Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications now known to elevate cardiovascular risk.
For each 30-day period, the investigators were then able to track and compare cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.
The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.
Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had up to 40 excess cardiovascular events per year – about half of them fatal – that were attributable to starting the medication. Although that group had the highest absolute risk, however, “the relative risks were highest in those with the lowest baseline risk,” wrote the investigators.
In addition to looking at rates of MACE, secondary outcomes for the study included evaluating the association between medication use or non-use and each individual component of the composite primary outcome. These included first-time occurrences of the nonfatal endpoints of atrial fibrillation or flutter, ischemic (but not hemorrhagic) stroke, heart failure, and myocardial infarction. Cardiac death was death from any cardiac cause.
“Supporting use of a combined endpoint, event rates consistently increased for all individual outcomes” for diclofenac initiators compared with those who did not start an NSAID, wrote Dr. Schmidt and his colleagues.
Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease, and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, aged a mean 48-56 years, had to be at least 18 years of age and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6%-46.3% of the cohorts.
Dr. Schmidt, of Aarhus (Denmark) University, and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a state that is known to be prothrombotic, and also associated with blood pressure elevation, atherogenesis, and worsening of heart failure.
Diclofenac and ibuprofen had similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, or no medication.
“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.
“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”
The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.
SOURCE: Schmidt M et al. BMJ 2018;362:k3426
Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE) compared with individuals who didn’t initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4-1.7).
The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with those starting ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1-1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE compared with initiating naproxen (95% CI, 1.1-1.5).
“Diclofenac is the most frequently used NSAID in low-, middle-, and high-income countries and is available over the counter in most countries; therefore, its cardiovascular risk profile is of major clinical and public health importance,” wrote Dr. Schmidt and his coauthors.
In all, the study included 1,370,832 individuals who initiated diclofenac, 3,878,454 ibuprofen initiators, 291,490 naproxen initiators, and 764,781 acetaminophen initiators. Those starting diclofenac were compared with those starting other medications, and with 1,303,209 individuals who sought health care but did not start one of the medications.
The researchers used the longstanding and complete Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications now known to elevate cardiovascular risk.
For each 30-day period, the investigators were then able to track and compare cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.
The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.
Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had up to 40 excess cardiovascular events per year – about half of them fatal – that were attributable to starting the medication. Although that group had the highest absolute risk, however, “the relative risks were highest in those with the lowest baseline risk,” wrote the investigators.
In addition to looking at rates of MACE, secondary outcomes for the study included evaluating the association between medication use or non-use and each individual component of the composite primary outcome. These included first-time occurrences of the nonfatal endpoints of atrial fibrillation or flutter, ischemic (but not hemorrhagic) stroke, heart failure, and myocardial infarction. Cardiac death was death from any cardiac cause.
“Supporting use of a combined endpoint, event rates consistently increased for all individual outcomes” for diclofenac initiators compared with those who did not start an NSAID, wrote Dr. Schmidt and his colleagues.
Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease, and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, aged a mean 48-56 years, had to be at least 18 years of age and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6%-46.3% of the cohorts.
Dr. Schmidt, of Aarhus (Denmark) University, and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a state that is known to be prothrombotic, and also associated with blood pressure elevation, atherogenesis, and worsening of heart failure.
Diclofenac and ibuprofen had similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, or no medication.
“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.
“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”
The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.
SOURCE: Schmidt M et al. BMJ 2018;362:k3426
Those beginning diclofenac had a 50% increased 30-day risk for a composite outcome of major adverse cardiovascular events (MACE) compared with individuals who didn’t initiate an NSAID or acetaminophen (95% confidence interval for incidence rate ratio, 1.4-1.7).
The risk was still significantly elevated when the study’s first author, Morten Schmidt, MD, and his colleagues compared diclofenac initiation with beginning other NSAIDs or acetaminophen. Compared with those starting ibuprofen or acetaminophen, the MACE risk was elevated 20% in diclofenac initiators (95% CI, 1.1-1.3 for both). Initiating diclofenac was associated with 30% greater risk for MACE compared with initiating naproxen (95% CI, 1.1-1.5).
“Diclofenac is the most frequently used NSAID in low-, middle-, and high-income countries and is available over the counter in most countries; therefore, its cardiovascular risk profile is of major clinical and public health importance,” wrote Dr. Schmidt and his coauthors.
In all, the study included 1,370,832 individuals who initiated diclofenac, 3,878,454 ibuprofen initiators, 291,490 naproxen initiators, and 764,781 acetaminophen initiators. Those starting diclofenac were compared with those starting other medications, and with 1,303,209 individuals who sought health care but did not start one of the medications.
The researchers used the longstanding and complete Danish health registry system to their advantage in designing a cohort trial that was modeled to resemble a clinical trial. For each month, beginning in 1996 and continuing through 2016, Dr. Schmidt and his collaborators assembled propensity-matched cohorts of individuals to compare each study group. The study design achieved many of the aims of a clinical trial while working within the ethical constraints of studying medications now known to elevate cardiovascular risk.
For each 30-day period, the investigators were then able to track and compare cardiovascular outcomes for each group. Each month, data for a new cohort were collected, beginning a new “clinical trial.” Individuals could be included in more than one month’s worth of “trial” data as long as they continued to meet inclusion criteria.
The completeness of Danish health data meant that the researchers were confident in data about comorbidities, other prescription medications, and outcomes.
Dr. Schmidt and his colleagues performed subgroup and sensitivity analyses to look at the extent to which preexisting risks for cardiovascular disease mediated MACE risk on diclofenac initiation. They found that diclofenac initiators in the highest risk group had up to 40 excess cardiovascular events per year – about half of them fatal – that were attributable to starting the medication. Although that group had the highest absolute risk, however, “the relative risks were highest in those with the lowest baseline risk,” wrote the investigators.
In addition to looking at rates of MACE, secondary outcomes for the study included evaluating the association between medication use or non-use and each individual component of the composite primary outcome. These included first-time occurrences of the nonfatal endpoints of atrial fibrillation or flutter, ischemic (but not hemorrhagic) stroke, heart failure, and myocardial infarction. Cardiac death was death from any cardiac cause.
“Supporting use of a combined endpoint, event rates consistently increased for all individual outcomes” for diclofenac initiators compared with those who did not start an NSAID, wrote Dr. Schmidt and his colleagues.
Individuals were excluded if they had known cardiovascular, kidney, liver, or ulcer disease, and if they had malignancy or serious mental health diagnoses such as dementia or schizophrenia. Participants, aged a mean 48-56 years, had to be at least 18 years of age and could not have filled a prescription for an NSAID within the previous 12 months. Men made up 36.6%-46.3% of the cohorts.
Dr. Schmidt, of Aarhus (Denmark) University, and his collaborators said that in comparison with other NSAIDs, the short half-life of diclofenac means that a supratherapeutic plasma concentration of diclofenac soon after initiation achieves not just cyclooxygenase-2 (COX-2), but also COX-1 inhibition. However, after those high levels fall, patients taking diclofenac spend a substantial period of time with unopposed COX-2 inhibition, a state that is known to be prothrombotic, and also associated with blood pressure elevation, atherogenesis, and worsening of heart failure.
Diclofenac and ibuprofen had similar gastrointestinal bleeding risks, and both medications were associated with a higher risk of bleeding than were ibuprofen, acetaminophen, or no medication.
“Comparing diclofenac initiation with no NSAID initiation, the consistency between our results and those of previous meta-analyses of both trial and observational data provides strong evidence to guide clinical decision making,” said Dr. Schmidt and his coauthors.
“Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs,” noted the investigators. “It is time to acknowledge the potential health risk of diclofenac and to reduce its use.”
The study was funded by the Department of Clinical Epidemiology Research Foundation, University of Aarhus, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.
SOURCE: Schmidt M et al. BMJ 2018;362:k3426
FROM BMJ
Key clinical point: Those starting diclofenac had increased risk for cardiovascular events or cardiac death.
Major finding: Risk for major adverse cardiovascular events was increased by 50% compared with noninitiators.
Study details: Retrospective propensity-matched cohort study using national databases and registries.
Disclosures: The study was supported by the Department of Clinical Epidemiology Research Foundation of the University of Aarhus, Denmark, and by the Program for Clinical Research Infrastructure, funded by the Lundbeck Foundation, Novo Nordisk Foundation, and the Danish Research Council. The authors reported that they had no relevant conflicts of interest.
Source: Schmidt M et al. BMJ 2018;362:k3426.
RA, JIA may raise risk of preterm delivery
according to a study examining autoimmune disease in pregnancy. Corticosteroid use in any trimester increased that risk from 100%-400%, regardless of how active the arthritis was.
The study found that women with RA had more than double the risk for preterm delivery, compared with a cohort without autoimmune disease (relative risk, 2.09; 95% confidence interval, 1.50-2.91). For women with juvenile idiopathic arthritis (JIA), the relative risk was 1.81 for preterm delivery (95% CI, 1.14-2.89).
The prospective cohort study, part of the Organization of Teratology Information Specialists Autoimmune Disease in Pregnancy Project, enrolled 657 women with RA and 170 women with JIA. The study also included a comparison group of 564 women without autoimmune disease. All of those included in the study were enrolled before 19 weeks’ gestation and delivered live-born infants during 2004-2017.
The study adds to a clinically important area of research that has yielded sometimes conflicting results; clarity has also been impeded by a variety of methodologies. Though several analyses have shown higher risk of preterm delivery in women with RA, not all studies have adjusted for medication use and disease activity, Chelsey F. Smith, MD, and her coauthors wrote in Arthritis Care & Research. Further, how women with JIA fare in pregnancy has not been well studied, they said.
Dr. Smith, a rheumatologist at the University of California, San Diego, and her colleagues included many baseline covariates in their analysis of pregnancy outcomes; these included maternal age and race, socioeconomic status, body mass index, previous adverse pregnancy outcomes, and comorbidities, including autoimmune disease. Adverse pregnancy outcomes during the studied pregnancy were also included as covariates, and deliveries were considered preterm if labor began before 37 weeks’ gestation.
For women with RA, a higher active disease score at any point during pregnancy was associated with a significantly higher risk of preterm delivery, even after adjustment for other potential risk factors, including first-trimester corticosteroid use (adjusted risk ratio, 1.52; 95% CI, 1.06-2.18). The persistence of this association, wrote Dr. Smith and her colleagues, implies “that active disease in RA may contribute to [preterm delivery] independent of medications,” perhaps through the action of proinflammatory cytokines that may stimulate prostaglandins and provoke uterine contractions.
The researchers found, though, that this association between disease activity and risk for preterm birth did not hold true for women with JIA, leaving part of the mystery unsolved.
However, women with both RA and JIA who used corticosteroids in any trimester were more likely to have a preterm delivery, as were women with JIA who used NSAIDs in the first trimester of pregnancy. The use of disease-modifying antirheumatic drugs (DMARDs) and biologics in any trimester did not confer increased risk for preterm delivery in women with either disease state.
There were other differences between the groups: Women with JIA were overall younger, but had more prepregnancy hypertension, which “may have contributed to the elevated incidence of preeclampsia seen in this group,” the investigators wrote. Fever was more common in women with JIA, and had an independent association with preterm delivery, as did first trimester NSAID use in this group alone.
Dr. Smith and her colleagues hypothesized that the relative heterogeneity of the JIA group may mean that disease activity still influenced outcomes.
Among other comorbidities, gestational diabetes (GDM) was more common in the RA group than in the JIA group or the comparison cohort, and was associated with a significantly higher risk for preterm delivery in women with RA, even after accounting for preeclampsia and hypertension in a multivariate analysis.
Dr. Smith and her colleagues pointed out that it was difficult to account for physician behavior in managing pregnancy in these high-risk women. “Additionally, given that women with both RA and GDM are at a particularly high risk for perinatal complications, we can speculate that the obstetricians in this group were perhaps more aggressive about inducing at an earlier gestational age than in other groups, but this information was not available in the dataset.”
Through phone interviews, investigators obtained information about prescription and nonprescription medication use during pregnancy; women were also asked about use of other substances and occupational exposures, infections, and prenatal testing and other medical procedures. Another telephone interview conducted soon after delivery asked about birth outcomes. Abstracted medical record data were used to verify and supplement the interview information.
When looking at treatments used, Dr. Smith and her colleagues grouped autoimmune disease medications into DMARDs, non-DMARD biologic medications, corticosteroids, and NSAIDs.
Disease activity assessment, conducted at intake and at 32 weeks’ gestation, used the Health Assessment Questionnaire, pain scores, and patient global disease activity to calculate a Patient Activity Scale score ranging from 0 to 10. Patients with a score over 3.7 were classified as having high disease activity.
Dr. Smith and her colleagues said that the study’s strengths included its prospective design and robust statistical schema. Also, using data about corticosteroid use and disease activity earlier in pregnancy avoided the inclusion of a reverse causation effect, where systemic inflammatory changes associated with preterm delivery might provoke more disease activity and a consequent boost in corticosteroid use.
However, the researchers said, the overall numbers of participants with preterm delivery was relatively small, and the JIA cohort was small as well.
“Further analyses are necessary to look at other categories of arthritis affecting women of childbearing age, racial disparities in these populations, as well as the influence of disease activity in the later stages of pregnancy on other perinatal factors” that can contribute to preterm delivery, said Dr. Smith and her colleagues.
The collaborative research group that collected data for the study receives research funding from several pharmaceutical companies. None of the authors reported any personal conflicts of interest.
SOURCE: Smith CF et al. Arthritis Care Res. 2018 Aug 21. doi: 10.1002/acr.23730.
according to a study examining autoimmune disease in pregnancy. Corticosteroid use in any trimester increased that risk from 100%-400%, regardless of how active the arthritis was.
The study found that women with RA had more than double the risk for preterm delivery, compared with a cohort without autoimmune disease (relative risk, 2.09; 95% confidence interval, 1.50-2.91). For women with juvenile idiopathic arthritis (JIA), the relative risk was 1.81 for preterm delivery (95% CI, 1.14-2.89).
The prospective cohort study, part of the Organization of Teratology Information Specialists Autoimmune Disease in Pregnancy Project, enrolled 657 women with RA and 170 women with JIA. The study also included a comparison group of 564 women without autoimmune disease. All of those included in the study were enrolled before 19 weeks’ gestation and delivered live-born infants during 2004-2017.
The study adds to a clinically important area of research that has yielded sometimes conflicting results; clarity has also been impeded by a variety of methodologies. Though several analyses have shown higher risk of preterm delivery in women with RA, not all studies have adjusted for medication use and disease activity, Chelsey F. Smith, MD, and her coauthors wrote in Arthritis Care & Research. Further, how women with JIA fare in pregnancy has not been well studied, they said.
Dr. Smith, a rheumatologist at the University of California, San Diego, and her colleagues included many baseline covariates in their analysis of pregnancy outcomes; these included maternal age and race, socioeconomic status, body mass index, previous adverse pregnancy outcomes, and comorbidities, including autoimmune disease. Adverse pregnancy outcomes during the studied pregnancy were also included as covariates, and deliveries were considered preterm if labor began before 37 weeks’ gestation.
For women with RA, a higher active disease score at any point during pregnancy was associated with a significantly higher risk of preterm delivery, even after adjustment for other potential risk factors, including first-trimester corticosteroid use (adjusted risk ratio, 1.52; 95% CI, 1.06-2.18). The persistence of this association, wrote Dr. Smith and her colleagues, implies “that active disease in RA may contribute to [preterm delivery] independent of medications,” perhaps through the action of proinflammatory cytokines that may stimulate prostaglandins and provoke uterine contractions.
The researchers found, though, that this association between disease activity and risk for preterm birth did not hold true for women with JIA, leaving part of the mystery unsolved.
However, women with both RA and JIA who used corticosteroids in any trimester were more likely to have a preterm delivery, as were women with JIA who used NSAIDs in the first trimester of pregnancy. The use of disease-modifying antirheumatic drugs (DMARDs) and biologics in any trimester did not confer increased risk for preterm delivery in women with either disease state.
There were other differences between the groups: Women with JIA were overall younger, but had more prepregnancy hypertension, which “may have contributed to the elevated incidence of preeclampsia seen in this group,” the investigators wrote. Fever was more common in women with JIA, and had an independent association with preterm delivery, as did first trimester NSAID use in this group alone.
Dr. Smith and her colleagues hypothesized that the relative heterogeneity of the JIA group may mean that disease activity still influenced outcomes.
Among other comorbidities, gestational diabetes (GDM) was more common in the RA group than in the JIA group or the comparison cohort, and was associated with a significantly higher risk for preterm delivery in women with RA, even after accounting for preeclampsia and hypertension in a multivariate analysis.
Dr. Smith and her colleagues pointed out that it was difficult to account for physician behavior in managing pregnancy in these high-risk women. “Additionally, given that women with both RA and GDM are at a particularly high risk for perinatal complications, we can speculate that the obstetricians in this group were perhaps more aggressive about inducing at an earlier gestational age than in other groups, but this information was not available in the dataset.”
Through phone interviews, investigators obtained information about prescription and nonprescription medication use during pregnancy; women were also asked about use of other substances and occupational exposures, infections, and prenatal testing and other medical procedures. Another telephone interview conducted soon after delivery asked about birth outcomes. Abstracted medical record data were used to verify and supplement the interview information.
When looking at treatments used, Dr. Smith and her colleagues grouped autoimmune disease medications into DMARDs, non-DMARD biologic medications, corticosteroids, and NSAIDs.
Disease activity assessment, conducted at intake and at 32 weeks’ gestation, used the Health Assessment Questionnaire, pain scores, and patient global disease activity to calculate a Patient Activity Scale score ranging from 0 to 10. Patients with a score over 3.7 were classified as having high disease activity.
Dr. Smith and her colleagues said that the study’s strengths included its prospective design and robust statistical schema. Also, using data about corticosteroid use and disease activity earlier in pregnancy avoided the inclusion of a reverse causation effect, where systemic inflammatory changes associated with preterm delivery might provoke more disease activity and a consequent boost in corticosteroid use.
However, the researchers said, the overall numbers of participants with preterm delivery was relatively small, and the JIA cohort was small as well.
“Further analyses are necessary to look at other categories of arthritis affecting women of childbearing age, racial disparities in these populations, as well as the influence of disease activity in the later stages of pregnancy on other perinatal factors” that can contribute to preterm delivery, said Dr. Smith and her colleagues.
The collaborative research group that collected data for the study receives research funding from several pharmaceutical companies. None of the authors reported any personal conflicts of interest.
SOURCE: Smith CF et al. Arthritis Care Res. 2018 Aug 21. doi: 10.1002/acr.23730.
according to a study examining autoimmune disease in pregnancy. Corticosteroid use in any trimester increased that risk from 100%-400%, regardless of how active the arthritis was.
The study found that women with RA had more than double the risk for preterm delivery, compared with a cohort without autoimmune disease (relative risk, 2.09; 95% confidence interval, 1.50-2.91). For women with juvenile idiopathic arthritis (JIA), the relative risk was 1.81 for preterm delivery (95% CI, 1.14-2.89).
The prospective cohort study, part of the Organization of Teratology Information Specialists Autoimmune Disease in Pregnancy Project, enrolled 657 women with RA and 170 women with JIA. The study also included a comparison group of 564 women without autoimmune disease. All of those included in the study were enrolled before 19 weeks’ gestation and delivered live-born infants during 2004-2017.
The study adds to a clinically important area of research that has yielded sometimes conflicting results; clarity has also been impeded by a variety of methodologies. Though several analyses have shown higher risk of preterm delivery in women with RA, not all studies have adjusted for medication use and disease activity, Chelsey F. Smith, MD, and her coauthors wrote in Arthritis Care & Research. Further, how women with JIA fare in pregnancy has not been well studied, they said.
Dr. Smith, a rheumatologist at the University of California, San Diego, and her colleagues included many baseline covariates in their analysis of pregnancy outcomes; these included maternal age and race, socioeconomic status, body mass index, previous adverse pregnancy outcomes, and comorbidities, including autoimmune disease. Adverse pregnancy outcomes during the studied pregnancy were also included as covariates, and deliveries were considered preterm if labor began before 37 weeks’ gestation.
For women with RA, a higher active disease score at any point during pregnancy was associated with a significantly higher risk of preterm delivery, even after adjustment for other potential risk factors, including first-trimester corticosteroid use (adjusted risk ratio, 1.52; 95% CI, 1.06-2.18). The persistence of this association, wrote Dr. Smith and her colleagues, implies “that active disease in RA may contribute to [preterm delivery] independent of medications,” perhaps through the action of proinflammatory cytokines that may stimulate prostaglandins and provoke uterine contractions.
The researchers found, though, that this association between disease activity and risk for preterm birth did not hold true for women with JIA, leaving part of the mystery unsolved.
However, women with both RA and JIA who used corticosteroids in any trimester were more likely to have a preterm delivery, as were women with JIA who used NSAIDs in the first trimester of pregnancy. The use of disease-modifying antirheumatic drugs (DMARDs) and biologics in any trimester did not confer increased risk for preterm delivery in women with either disease state.
There were other differences between the groups: Women with JIA were overall younger, but had more prepregnancy hypertension, which “may have contributed to the elevated incidence of preeclampsia seen in this group,” the investigators wrote. Fever was more common in women with JIA, and had an independent association with preterm delivery, as did first trimester NSAID use in this group alone.
Dr. Smith and her colleagues hypothesized that the relative heterogeneity of the JIA group may mean that disease activity still influenced outcomes.
Among other comorbidities, gestational diabetes (GDM) was more common in the RA group than in the JIA group or the comparison cohort, and was associated with a significantly higher risk for preterm delivery in women with RA, even after accounting for preeclampsia and hypertension in a multivariate analysis.
Dr. Smith and her colleagues pointed out that it was difficult to account for physician behavior in managing pregnancy in these high-risk women. “Additionally, given that women with both RA and GDM are at a particularly high risk for perinatal complications, we can speculate that the obstetricians in this group were perhaps more aggressive about inducing at an earlier gestational age than in other groups, but this information was not available in the dataset.”
Through phone interviews, investigators obtained information about prescription and nonprescription medication use during pregnancy; women were also asked about use of other substances and occupational exposures, infections, and prenatal testing and other medical procedures. Another telephone interview conducted soon after delivery asked about birth outcomes. Abstracted medical record data were used to verify and supplement the interview information.
When looking at treatments used, Dr. Smith and her colleagues grouped autoimmune disease medications into DMARDs, non-DMARD biologic medications, corticosteroids, and NSAIDs.
Disease activity assessment, conducted at intake and at 32 weeks’ gestation, used the Health Assessment Questionnaire, pain scores, and patient global disease activity to calculate a Patient Activity Scale score ranging from 0 to 10. Patients with a score over 3.7 were classified as having high disease activity.
Dr. Smith and her colleagues said that the study’s strengths included its prospective design and robust statistical schema. Also, using data about corticosteroid use and disease activity earlier in pregnancy avoided the inclusion of a reverse causation effect, where systemic inflammatory changes associated with preterm delivery might provoke more disease activity and a consequent boost in corticosteroid use.
However, the researchers said, the overall numbers of participants with preterm delivery was relatively small, and the JIA cohort was small as well.
“Further analyses are necessary to look at other categories of arthritis affecting women of childbearing age, racial disparities in these populations, as well as the influence of disease activity in the later stages of pregnancy on other perinatal factors” that can contribute to preterm delivery, said Dr. Smith and her colleagues.
The collaborative research group that collected data for the study receives research funding from several pharmaceutical companies. None of the authors reported any personal conflicts of interest.
SOURCE: Smith CF et al. Arthritis Care Res. 2018 Aug 21. doi: 10.1002/acr.23730.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: The risk of preterm delivery was increased in women with RA and juvenile idiopathic arthritis.
Major finding: The risk ratio for preterm delivery in women with RA was 2.09.
Study details: A prospective cohort study of 657 women with RA, 170 women with juvenile idiopathic arthritis, and 564 women without autoimmune disease.
Disclosures: The study was part of the Organization of Teratology Information Specialists Autoimmune Disease in Pregnancy Project, which receives research funding from several pharmaceutical companies. None of the authors reported any personal conflicts of interest.
Source: Smith CF et al. Arthritis Care Res. 2018 Aug 21. doi: 10.1002/acr.23730.