Steve Cimino

Although the 2010 Patient Protection and Affordable Care Act attempted to close the coverage gap for prescription drugs, a new study has found that yearly price increases for expensive treatments like rheumatoid arthritis biologics have kept out-of-pocket spending high for patients enrolled in Medicare Part D.

“As the coverage gap is now considered closed, our results suggest a need for out-of-pocket maximums in the catastrophic phase to limit older Americans’ yearly financial burden and allow them to better estimate their annual drug costs,” wrote coauthors Alexandra Erath and Stacie B. Dusetzina, PhD, of Vanderbilt University in Nashville, Tenn. The study was published in JAMA Network Open.

To determine if closing the Medicare Part D coverage gap lowered out-of-pocket costs as anticipated, the researchers embarked on a cross-sectional study of Medicare data from the first quarter of each calendar year from 2010 to 2019. They analyzed the costs of 17 RA biologic drug and strength combinations, calculating the median point-of-sale price per fill for each drug and adjusting for medical inflation.

From 2010 to 2019, the median price per fill increased for all 17 drugs studied. With the exception of the 100-mg/1-mL golimumab (Simponi) autoinjector, every drug that had been on the market for 5 years or longer had a price increase of more than 20%. For the six drugs that have been on the market since 2010 – 200 mg of certolizumab pegol (Cimzia), 25 mg of etanercept (Enbrel), 50 mg of etanercept, 20 mg/0.4 mL of adalimumab (Humira), 40 mg/0.8 mL of adalimumab, and 50 mg/0.5 mL of golimumab – the median list price increased by a mean of 160% (standard deviation [SD], 17%; range, 136%-180%).

Mean (SD) annual out-of-pocket spending for those six drugs did decrease from $6,108 (SD, $234; range, $5,647-6,282) in 2010 to $4,801 (SD, $620; range, $3,594-$5,196) in 2019. However, the most significant decrease actually occurred between 2010 and 2011, when out-of-pocket spending dropped to $4,026 because the Affordable Care Act’s 50% manufacturer rebate for brand-name drugs filled in the coverage gap. This meant there was actually a mean increase of 19% in out-of-pocket costs from 2011 to 2019.

“This is the same story as the EpiPen,” said Maria Greenwald, MD, of Desert Medical Advances in Palm Desert, Calif., in an interview. “Patients have to have it, so you’re going to pay $600 even if you used to pay $50. Why do pharmaceutical companies keep raising their prices? Because they can. There’s no cap on list prices. And these drugs are miracles. They’re the difference between a high quality of life and being bound to a wheelchair. These patients don’t sleep without them. They’ll do whatever they can to pay for them, and so the prices continue to go up.”

This study reinforces the need for physicians to advocate for affordable biologics across the board, wrote Joel Lexchin, MD, of York University in Toronto in an accompanying editorial (doi: 10.1001/jamanetworkopen.2020.4753).

“Price increases for biologics do not only affect patients with rheumatologic conditions,” Dr. Lexchin noted, citing how the cost of multiple sclerosis therapies increased by thousands of dollars from the mid-1990s to 2013. In addition, although biologics make up a single-digit percentage of prescriptions in the United States, he highlighted that “they are responsible for $120 billion or 37% of net drug spending and, since 2014, for 93% of the overall growth in total spending.”

When it comes to potential solutions, he said that Medicare should negotiate directly with drug companies, that substitutions with biosimilars should become mandatory whenever possible, and that pharmaceutical companies should publicly validate their alleged research and development expenses. “Biologics can be transformational treatments,” he wrote, “but only if they are affordable at both the individual and societal levels.”

The authors shared their study’s potential limitations, including relying on list prices that do not factor in rebates and focusing on a single biologic filled every month rather than all treatments filled under Medicare, which could “result in our underestimating out-of-pocket spending by patients.” In addition, although a growing RA biosimilar market could increase price competition and lower costs, they added that progress in that area is limited by “aggressive litigation by the biologic manufacturers and an insufficient number of competitors to markedly affect price.”

The study was supported by the Commonwealth Fund and the Leukemia and Lymphoma Society. Dr. Dusetzina reported receiving grants from Arnold Ventures and personal fees from the Institute for Clinical and Economic Review.

SOURCE: Erath A et al. JAMA Netw Open. 2020 Apr 27. doi: 10.1001/jamanetworkopen.2020.3969.

Although the 2010 Patient Protection and Affordable Care Act attempted to close the coverage gap for prescription drugs, a new study has found that yearly price increases for expensive treatments like rheumatoid arthritis biologics have kept out-of-pocket spending high for patients enrolled in Medicare Part D.

“As the coverage gap is now considered closed, our results suggest a need for out-of-pocket maximums in the catastrophic phase to limit older Americans’ yearly financial burden and allow them to better estimate their annual drug costs,” wrote coauthors Alexandra Erath and Stacie B. Dusetzina, PhD, of Vanderbilt University in Nashville, Tenn. The study was published in JAMA Network Open.

To determine if closing the Medicare Part D coverage gap lowered out-of-pocket costs as anticipated, the researchers embarked on a cross-sectional study of Medicare data from the first quarter of each calendar year from 2010 to 2019. They analyzed the costs of 17 RA biologic drug and strength combinations, calculating the median point-of-sale price per fill for each drug and adjusting for medical inflation.

From 2010 to 2019, the median price per fill increased for all 17 drugs studied. With the exception of the 100-mg/1-mL golimumab (Simponi) autoinjector, every drug that had been on the market for 5 years or longer had a price increase of more than 20%. For the six drugs that have been on the market since 2010 – 200 mg of certolizumab pegol (Cimzia), 25 mg of etanercept (Enbrel), 50 mg of etanercept, 20 mg/0.4 mL of adalimumab (Humira), 40 mg/0.8 mL of adalimumab, and 50 mg/0.5 mL of golimumab – the median list price increased by a mean of 160% (standard deviation [SD], 17%; range, 136%-180%).

Mean (SD) annual out-of-pocket spending for those six drugs did decrease from $6,108 (SD, $234; range, $5,647-6,282) in 2010 to $4,801 (SD, $620; range, $3,594-$5,196) in 2019. However, the most significant decrease actually occurred between 2010 and 2011, when out-of-pocket spending dropped to $4,026 because the Affordable Care Act’s 50% manufacturer rebate for brand-name drugs filled in the coverage gap. This meant there was actually a mean increase of 19% in out-of-pocket costs from 2011 to 2019.

“This is the same story as the EpiPen,” said Maria Greenwald, MD, of Desert Medical Advances in Palm Desert, Calif., in an interview. “Patients have to have it, so you’re going to pay $600 even if you used to pay $50. Why do pharmaceutical companies keep raising their prices? Because they can. There’s no cap on list prices. And these drugs are miracles. They’re the difference between a high quality of life and being bound to a wheelchair. These patients don’t sleep without them. They’ll do whatever they can to pay for them, and so the prices continue to go up.”

This study reinforces the need for physicians to advocate for affordable biologics across the board, wrote Joel Lexchin, MD, of York University in Toronto in an accompanying editorial (doi: 10.1001/jamanetworkopen.2020.4753).

“Price increases for biologics do not only affect patients with rheumatologic conditions,” Dr. Lexchin noted, citing how the cost of multiple sclerosis therapies increased by thousands of dollars from the mid-1990s to 2013. In addition, although biologics make up a single-digit percentage of prescriptions in the United States, he highlighted that “they are responsible for $120 billion or 37% of net drug spending and, since 2014, for 93% of the overall growth in total spending.”

When it comes to potential solutions, he said that Medicare should negotiate directly with drug companies, that substitutions with biosimilars should become mandatory whenever possible, and that pharmaceutical companies should publicly validate their alleged research and development expenses. “Biologics can be transformational treatments,” he wrote, “but only if they are affordable at both the individual and societal levels.”

The authors shared their study’s potential limitations, including relying on list prices that do not factor in rebates and focusing on a single biologic filled every month rather than all treatments filled under Medicare, which could “result in our underestimating out-of-pocket spending by patients.” In addition, although a growing RA biosimilar market could increase price competition and lower costs, they added that progress in that area is limited by “aggressive litigation by the biologic manufacturers and an insufficient number of competitors to markedly affect price.”

The study was supported by the Commonwealth Fund and the Leukemia and Lymphoma Society. Dr. Dusetzina reported receiving grants from Arnold Ventures and personal fees from the Institute for Clinical and Economic Review.

SOURCE: Erath A et al. JAMA Netw Open. 2020 Apr 27. doi: 10.1001/jamanetworkopen.2020.3969.

Although the 2010 Patient Protection and Affordable Care Act attempted to close the coverage gap for prescription drugs, a new study has found that yearly price increases for expensive treatments like rheumatoid arthritis biologics have kept out-of-pocket spending high for patients enrolled in Medicare Part D.

“As the coverage gap is now considered closed, our results suggest a need for out-of-pocket maximums in the catastrophic phase to limit older Americans’ yearly financial burden and allow them to better estimate their annual drug costs,” wrote coauthors Alexandra Erath and Stacie B. Dusetzina, PhD, of Vanderbilt University in Nashville, Tenn. The study was published in JAMA Network Open.

To determine if closing the Medicare Part D coverage gap lowered out-of-pocket costs as anticipated, the researchers embarked on a cross-sectional study of Medicare data from the first quarter of each calendar year from 2010 to 2019. They analyzed the costs of 17 RA biologic drug and strength combinations, calculating the median point-of-sale price per fill for each drug and adjusting for medical inflation.

From 2010 to 2019, the median price per fill increased for all 17 drugs studied. With the exception of the 100-mg/1-mL golimumab (Simponi) autoinjector, every drug that had been on the market for 5 years or longer had a price increase of more than 20%. For the six drugs that have been on the market since 2010 – 200 mg of certolizumab pegol (Cimzia), 25 mg of etanercept (Enbrel), 50 mg of etanercept, 20 mg/0.4 mL of adalimumab (Humira), 40 mg/0.8 mL of adalimumab, and 50 mg/0.5 mL of golimumab – the median list price increased by a mean of 160% (standard deviation [SD], 17%; range, 136%-180%).

Mean (SD) annual out-of-pocket spending for those six drugs did decrease from $6,108 (SD, $234; range, $5,647-6,282) in 2010 to $4,801 (SD, $620; range, $3,594-$5,196) in 2019. However, the most significant decrease actually occurred between 2010 and 2011, when out-of-pocket spending dropped to $4,026 because the Affordable Care Act’s 50% manufacturer rebate for brand-name drugs filled in the coverage gap. This meant there was actually a mean increase of 19% in out-of-pocket costs from 2011 to 2019.

“This is the same story as the EpiPen,” said Maria Greenwald, MD, of Desert Medical Advances in Palm Desert, Calif., in an interview. “Patients have to have it, so you’re going to pay $600 even if you used to pay $50. Why do pharmaceutical companies keep raising their prices? Because they can. There’s no cap on list prices. And these drugs are miracles. They’re the difference between a high quality of life and being bound to a wheelchair. These patients don’t sleep without them. They’ll do whatever they can to pay for them, and so the prices continue to go up.”

This study reinforces the need for physicians to advocate for affordable biologics across the board, wrote Joel Lexchin, MD, of York University in Toronto in an accompanying editorial (doi: 10.1001/jamanetworkopen.2020.4753).

“Price increases for biologics do not only affect patients with rheumatologic conditions,” Dr. Lexchin noted, citing how the cost of multiple sclerosis therapies increased by thousands of dollars from the mid-1990s to 2013. In addition, although biologics make up a single-digit percentage of prescriptions in the United States, he highlighted that “they are responsible for $120 billion or 37% of net drug spending and, since 2014, for 93% of the overall growth in total spending.”

When it comes to potential solutions, he said that Medicare should negotiate directly with drug companies, that substitutions with biosimilars should become mandatory whenever possible, and that pharmaceutical companies should publicly validate their alleged research and development expenses. “Biologics can be transformational treatments,” he wrote, “but only if they are affordable at both the individual and societal levels.”

The authors shared their study’s potential limitations, including relying on list prices that do not factor in rebates and focusing on a single biologic filled every month rather than all treatments filled under Medicare, which could “result in our underestimating out-of-pocket spending by patients.” In addition, although a growing RA biosimilar market could increase price competition and lower costs, they added that progress in that area is limited by “aggressive litigation by the biologic manufacturers and an insufficient number of competitors to markedly affect price.”

The study was supported by the Commonwealth Fund and the Leukemia and Lymphoma Society. Dr. Dusetzina reported receiving grants from Arnold Ventures and personal fees from the Institute for Clinical and Economic Review.

SOURCE: Erath A et al. JAMA Netw Open. 2020 Apr 27. doi: 10.1001/jamanetworkopen.2020.3969.

Several risk factors, including smoking, a previous severe hypoglycemic event, and poorly functioning kidneys, can lead to vision loss in patients with type 2 diabetes, according to new findings published in the Journal of Diabetes and its Complications.

“Smoking cessation strategies and optimal cardiometabolic risk factor management, including blood glucose lowering regimens that minimize hypoglycemia, appear important in preventing the loss of vision associated with type 2 diabetes,” wrote Jocelyn J. Drinkwater of the University of Western Australia, Perth, and coauthors, noting that all three noted risk factors were “potentially modifiable.”

To investigate the impact of type 2 diabetes and associated risk factors on vision, the researchers recruited 1,732 participants for the Fremantle Diabetes Study Phase II, of whom 1,551 patients had type 2 diabetes and underwent face-to-face and visual acuity assessments at baseline and at 2 and 4 years. Visual acuity was measured via the Bailey Lovie chart at a distance of 3 m in a well-lit room. Normal or near-normal vision was classified as a visual acuity of equal to or less than 6/19; visual impairment, a visual acuity of greater than 6/19 and equal to or less than 6/48; and blindness, a visual acuity of greater than 6/48. A change in vision was classified as a difference in visual acuity of more than 10 letters from baseline measurement.

Of the initial 1,551 participants, 31 were excluded because of missing baseline data for visual acuity. The remaining group comprised 52.2% men, the mean age was 65.6 years, and the median diabetes duration was 8.5 years (interquartile range, 2.9-15.8). At baseline, the prevalence of visual impairment was 1.8% (28 patients), and prevalence of blindness was 0.7% (11 patients), so those 39 patients were also excluded from further analysis.

After 4 years, 599 patients (39%) were excluded because of attrition or missing data; among them, 138 (23%) died before the follow-up.

The remaining 882 participants (58%) had their visual acuity measured. Among these patients, 62.2% were men, with a mean age of 65.1 years and an initial median diabetes duration of 7 years (IQR, 2.0-15.0). Their cumulative incidence of visual impairment was 0.9% (eight patients), and no patients with normal or near-normal vision had developed blindness. Cumulative incidence of vision loss was 2.9% (26), and 1.9% (17) had improved visual acuity.

After multivariable logistic regression to determine predictors for vision loss, the researchers found that participants who smoked at baseline were more than three times more likely to lose their vision (odds ratio, 3.17; 95% confidence interval, 1.15-8.76; P = .026). Although smoking was noted as a “well-recognized risk factor for ocular disease,” the authors added that ex-smokers did not have significantly higher odds of vision loss, compared with nonsmokers, suggesting that the “ocular damage caused by smoking may not be permanent.”

Participants who had suffered a severe hypoglycemic event before the study were five times more likely to lose their vision (OR, 5.59; 95% CI, 1.32-23.61; P = .019). The authors emphasized that severe hypoglycemia can worsen existing ischemic tissue damage or contribute to a long duration of poorly controlled diabetes, each of which could “increase the risk of ocular complications leading to impaired vision.”

The final notable risk factor was compromised kidney function, which is identified as a urinary albumin-creatinine ratio (uACR). The authors noted that the uACR has been associated with other ocular pathologies, such as retinopathy and macular edema, and that uACR may be a “surrogate marker of a variety of ocular diseases with shared risk factors, such as poor metabolic control, which have implications for vision.”

In regard to the possible limitations of the study, they authors noted that they had not used the “gold standard” Early Treatment Diabetic Retinopathy Study chart to assess visual acuity. In addition, although they had details on retinopathy, cataracts, and glaucoma status, they did not also consider less common ophthalmic conditions. Finally, as a survivor cohort, they acknowledged that they may have “underestimated the cumulative incidence” of vision issues in the participants.

The study was supported by the National Health and Medical Research Council of Australia. The authors reported no conflicts of interest.

SOURCE: Drinkwater JJ et al. J Diabetes Complications. 2020 Feb 20. doi: 10.1016/j.jdiacomp.2020.107560.

Several risk factors, including smoking, a previous severe hypoglycemic event, and poorly functioning kidneys, can lead to vision loss in patients with type 2 diabetes, according to new findings published in the Journal of Diabetes and its Complications.

“Smoking cessation strategies and optimal cardiometabolic risk factor management, including blood glucose lowering regimens that minimize hypoglycemia, appear important in preventing the loss of vision associated with type 2 diabetes,” wrote Jocelyn J. Drinkwater of the University of Western Australia, Perth, and coauthors, noting that all three noted risk factors were “potentially modifiable.”

To investigate the impact of type 2 diabetes and associated risk factors on vision, the researchers recruited 1,732 participants for the Fremantle Diabetes Study Phase II, of whom 1,551 patients had type 2 diabetes and underwent face-to-face and visual acuity assessments at baseline and at 2 and 4 years. Visual acuity was measured via the Bailey Lovie chart at a distance of 3 m in a well-lit room. Normal or near-normal vision was classified as a visual acuity of equal to or less than 6/19; visual impairment, a visual acuity of greater than 6/19 and equal to or less than 6/48; and blindness, a visual acuity of greater than 6/48. A change in vision was classified as a difference in visual acuity of more than 10 letters from baseline measurement.

Of the initial 1,551 participants, 31 were excluded because of missing baseline data for visual acuity. The remaining group comprised 52.2% men, the mean age was 65.6 years, and the median diabetes duration was 8.5 years (interquartile range, 2.9-15.8). At baseline, the prevalence of visual impairment was 1.8% (28 patients), and prevalence of blindness was 0.7% (11 patients), so those 39 patients were also excluded from further analysis.

After 4 years, 599 patients (39%) were excluded because of attrition or missing data; among them, 138 (23%) died before the follow-up.

The remaining 882 participants (58%) had their visual acuity measured. Among these patients, 62.2% were men, with a mean age of 65.1 years and an initial median diabetes duration of 7 years (IQR, 2.0-15.0). Their cumulative incidence of visual impairment was 0.9% (eight patients), and no patients with normal or near-normal vision had developed blindness. Cumulative incidence of vision loss was 2.9% (26), and 1.9% (17) had improved visual acuity.

After multivariable logistic regression to determine predictors for vision loss, the researchers found that participants who smoked at baseline were more than three times more likely to lose their vision (odds ratio, 3.17; 95% confidence interval, 1.15-8.76; P = .026). Although smoking was noted as a “well-recognized risk factor for ocular disease,” the authors added that ex-smokers did not have significantly higher odds of vision loss, compared with nonsmokers, suggesting that the “ocular damage caused by smoking may not be permanent.”

Participants who had suffered a severe hypoglycemic event before the study were five times more likely to lose their vision (OR, 5.59; 95% CI, 1.32-23.61; P = .019). The authors emphasized that severe hypoglycemia can worsen existing ischemic tissue damage or contribute to a long duration of poorly controlled diabetes, each of which could “increase the risk of ocular complications leading to impaired vision.”

The final notable risk factor was compromised kidney function, which is identified as a urinary albumin-creatinine ratio (uACR). The authors noted that the uACR has been associated with other ocular pathologies, such as retinopathy and macular edema, and that uACR may be a “surrogate marker of a variety of ocular diseases with shared risk factors, such as poor metabolic control, which have implications for vision.”

In regard to the possible limitations of the study, they authors noted that they had not used the “gold standard” Early Treatment Diabetic Retinopathy Study chart to assess visual acuity. In addition, although they had details on retinopathy, cataracts, and glaucoma status, they did not also consider less common ophthalmic conditions. Finally, as a survivor cohort, they acknowledged that they may have “underestimated the cumulative incidence” of vision issues in the participants.

The study was supported by the National Health and Medical Research Council of Australia. The authors reported no conflicts of interest.

SOURCE: Drinkwater JJ et al. J Diabetes Complications. 2020 Feb 20. doi: 10.1016/j.jdiacomp.2020.107560.

Several risk factors, including smoking, a previous severe hypoglycemic event, and poorly functioning kidneys, can lead to vision loss in patients with type 2 diabetes, according to new findings published in the Journal of Diabetes and its Complications.

“Smoking cessation strategies and optimal cardiometabolic risk factor management, including blood glucose lowering regimens that minimize hypoglycemia, appear important in preventing the loss of vision associated with type 2 diabetes,” wrote Jocelyn J. Drinkwater of the University of Western Australia, Perth, and coauthors, noting that all three noted risk factors were “potentially modifiable.”

To investigate the impact of type 2 diabetes and associated risk factors on vision, the researchers recruited 1,732 participants for the Fremantle Diabetes Study Phase II, of whom 1,551 patients had type 2 diabetes and underwent face-to-face and visual acuity assessments at baseline and at 2 and 4 years. Visual acuity was measured via the Bailey Lovie chart at a distance of 3 m in a well-lit room. Normal or near-normal vision was classified as a visual acuity of equal to or less than 6/19; visual impairment, a visual acuity of greater than 6/19 and equal to or less than 6/48; and blindness, a visual acuity of greater than 6/48. A change in vision was classified as a difference in visual acuity of more than 10 letters from baseline measurement.

Of the initial 1,551 participants, 31 were excluded because of missing baseline data for visual acuity. The remaining group comprised 52.2% men, the mean age was 65.6 years, and the median diabetes duration was 8.5 years (interquartile range, 2.9-15.8). At baseline, the prevalence of visual impairment was 1.8% (28 patients), and prevalence of blindness was 0.7% (11 patients), so those 39 patients were also excluded from further analysis.

After 4 years, 599 patients (39%) were excluded because of attrition or missing data; among them, 138 (23%) died before the follow-up.

The remaining 882 participants (58%) had their visual acuity measured. Among these patients, 62.2% were men, with a mean age of 65.1 years and an initial median diabetes duration of 7 years (IQR, 2.0-15.0). Their cumulative incidence of visual impairment was 0.9% (eight patients), and no patients with normal or near-normal vision had developed blindness. Cumulative incidence of vision loss was 2.9% (26), and 1.9% (17) had improved visual acuity.

After multivariable logistic regression to determine predictors for vision loss, the researchers found that participants who smoked at baseline were more than three times more likely to lose their vision (odds ratio, 3.17; 95% confidence interval, 1.15-8.76; P = .026). Although smoking was noted as a “well-recognized risk factor for ocular disease,” the authors added that ex-smokers did not have significantly higher odds of vision loss, compared with nonsmokers, suggesting that the “ocular damage caused by smoking may not be permanent.”

Participants who had suffered a severe hypoglycemic event before the study were five times more likely to lose their vision (OR, 5.59; 95% CI, 1.32-23.61; P = .019). The authors emphasized that severe hypoglycemia can worsen existing ischemic tissue damage or contribute to a long duration of poorly controlled diabetes, each of which could “increase the risk of ocular complications leading to impaired vision.”

The final notable risk factor was compromised kidney function, which is identified as a urinary albumin-creatinine ratio (uACR). The authors noted that the uACR has been associated with other ocular pathologies, such as retinopathy and macular edema, and that uACR may be a “surrogate marker of a variety of ocular diseases with shared risk factors, such as poor metabolic control, which have implications for vision.”

In regard to the possible limitations of the study, they authors noted that they had not used the “gold standard” Early Treatment Diabetic Retinopathy Study chart to assess visual acuity. In addition, although they had details on retinopathy, cataracts, and glaucoma status, they did not also consider less common ophthalmic conditions. Finally, as a survivor cohort, they acknowledged that they may have “underestimated the cumulative incidence” of vision issues in the participants.

The study was supported by the National Health and Medical Research Council of Australia. The authors reported no conflicts of interest.

SOURCE: Drinkwater JJ et al. J Diabetes Complications. 2020 Feb 20. doi: 10.1016/j.jdiacomp.2020.107560.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

A new guideline from the American College of Rheumatology offers the organization’s first clinical recommendations on how to manage reproductive health issues in patients with rheumatic and musculoskeletal diseases (RMDs).

Bruce Jancin/MDedge News

“With the development of this guideline, the ACR recognizes the key role of clinical rheumatologists not only in managing disease activity but also in understanding the interactions of RMDs and their therapies in the context of reproductive health,” wrote Lisa R. Sammaritano, MD, of Weill Cornell Medicine and the Hospital for Special Surgery in New York, and coauthors. The guideline was published in Arthritis & Rheumatology.

To develop an evidence-based guideline on reproductive health in RMD patients, the researchers embarked on a systematic review of studies in areas like contraception, pregnancy and lactation, assisted reproductive technology (ART), fertility preservation, and hormone therapy. The guideline contains 12 ungraded good practice statements and 131 graded recommendations, all developed through the Grading of Recommendations Assessment, Development, and Evaluation methodology.

In counseling patients about these areas of care, the guideline says that rheumatologists and other clinicians “must collaborate with specialists in the fields of obstetrics-gynecology, maternal-fetal medicine, and reproductive endocrinology and infertility.”

Mitchel L. Zoler/Frontline Medical News

“One thing this guideline does well is highlight the importance of involving maternal-fetal medicine colleagues,” Alison Cahill, MD, a professor in the department of women’s health at the University of Texas at Austin and a maternal-fetal medicine specialist within UT Health Austin’s Women’s Health Institute, said when asked for comment on the guideline. “We’re always very happy to see patients ahead of time who are planning pregnancy to be able to discuss what the care plan would look like. And specifically, to address medications, if required, for their rheumatologic care.

“As we learn more and more,” she added, “we’ve come to understand that most treatments and medications are actually safe or relatively safe to take in pregnancy. Certainly, the benefit of taking them outweighs any small or theoretic risks. On the flip side, the guideline does a nice job of highlighting the importance of good disease control, both at the time of conception and during pregnancy.”
 

Contraception

In regard to contraception, the guideline strongly recommends the use of effective contraceptives – with a conditional recommendation of IUDs or a subdermal progestin implant – in fertile women with a RMD who have neither systemic lupus erythematosus (SLE) nor positive antiphospholipid antibody (aPL). They also strongly recommend discussing the use of emergency contraception with all RMD patients.

For SLE patients, the guideline strongly recommends the use of effective contraceptives in those with stable or low disease activity who are not positive for aPL. They also strongly recommend progestin‐only or IUD contraceptives over combined estrogen‐progestin contraception. For aPL-positive patients, the guideline strongly recommends against combined estrogen‐progestin contraceptives and for levonorgestrel or copper IUDs or the progestin‐only pill.
 

Assisted reproductive technology

In regard to ART, the guideline strongly recommends proceeding as needed in aPL-negative women with uncomplicated, stable RMD who are on pregnancy‐compatible medications. They also strongly recommend deferring ART in any RMD patients with moderately or severely active disease.

For aPL-positive patients undergoing ART procedures, they strongly recommend prophylactic anticoagulation with heparin or low-molecular-weight heparin (LMWH) in women with obstetric antiphospholipid syndrome (APS) and therapeutic anticoagulation in women with thrombotic APS. In patients undergoing embryo and oocyte cryopreservation, they strongly recommend continuing immunosuppressive and biologic therapies – the exception being cyclophosphamide (CYC) – for anyone in stable condition.
 

Fertility preservation

In regard to fertility preservation in patients taking CYC, the guideline strongly suggests sperm cryopreservation as good practice prior to treatment. They also conditionally recommend monthly gonadotropin‐releasing hormone agonist cotherapy in premenopausal women with RMD.

Hormone therapy

In regard to menopause and hormone therapy, the guideline strongly suggests hormone therapy as good practice in postmenopausal women with RMD, without SLE or positive aPL, and who have severe vasomotor symptoms. Hormone therapy is conditionally recommended in patients with SLE, without positive aPL, and with no contraindications. For aPL-positive patients, they strongly recommend against hormone therapy in women with obstetric and/or thrombotic APS.

Pregnancy assessment and management

Among the many recommendations regarding pregnancy assessment and management, the guideline strongly suggests counseling women with RMD who are considering pregnancy to take into account the improved outcomes for pregnant women with low disease activity. They strongly recommend that women considering pregnancy should switch to pregnancy‐compatible medication and pause to assess its efficacy and tolerability before moving forward, along with strongly recommending that pregnant women with active disease initiate or continue a pregnancy‐compatible steroid‐sparing medication. They also recommend testing for anti‐Ro/SS-A and anti‐La/SS-B in women with SLE, Sjögren’s syndrome, systemic sclerosis, or rheumatoid arthritis, but only once and only before or early in the pregnancy.

For women with systemic sclerosis who develop scleroderma renal crisis during pregnancy, the authors strongly advise using ACE inhibitors or angiotensin receptor blockers “because the risk of maternal or fetal death with untreated disease is higher than the risk associated with use of these medications during pregnancy.”

Among women with SLE, the recommendations strongly call for testing either before or early in pregnancy for anticardiolipin antibody, anti–beta2-glycoprotein I, or positive lupus anticoagulant, as well as initiating or continuing hydroxychloroquine (HCQ) if possible. Starting in the first trimester, the authors also conditionally recommend that SLE patients take low-dose aspirin daily

For pregnant women who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the guideline conditionally recommends prophylactic treatment with low-dose aspirin daily to protect against preeclampsia. When obstetric APS criteria are met, the guideline strongly advises combined treatment with daily low-dose aspirin and prophylactic-dose heparin (or LMWH), as well as prophylactic-dose anticoagulation for 6-12 weeks post partum. When patients have thrombotic APS, this combination treatment should contain heparin dose at a therapeutic level throughout pregnancy and postpartum. However, the authors conditionally recommend against giving low-dose aspirin plus prophylactic-dose heparin to women without obstetric APS. For refractory obstetric APS, the guideline also contains recommendations that are conditionally against treatment with intravenous immunoglobulin or an increased LMWH dose and strongly against adding prednisone to prophylactic-dose heparin or LMWH and low-dose aspirin. In pregnant patients with primary APS, the authors conditionally advise adding HCQ to prophylactic-dose heparin or LMWH and low-dose aspirin therapy. However, women with aPL who do not meet APS criteria or have another indication for HCQ are conditionally advised against prophylactic treatment with the antimalarial.

For women with Anti-Ro/SS-A and/or anti-La/SS-B antibodies in pregnancy, there is conditional advice to use HCQ. When there is no history of an infant with complete heart block or neonatal lupus erythematosus among women with these antibodies, the guideline conditionally advises serial fetal echocardiography (less often than weekly) starting between 16 and 18 weeks and continuing through 26 weeks, but this should be weekly when there is a prior history. Treatment with oral dexamethasone 4 mg daily is conditionally advised when there is echocardiographic evidence of fetal first- or second-degree heart block, but dexamethasone is not recommended when complete heart block is present.

Finally, in regard to medication use, the authors strongly recommend that men who are planning to be fathers continue on HCQ, azathioprine, 6‐mercaptopurine, colchicine, or tumor necrosis factor inhibitors. Conditional treatment recommendations for men planning for pregnancy include methotrexate, mycophenolate mofetil/mycophenolic acid (MMF), leflunomide, sulfasalazine, calcineurin inhibitors, and NSAIDs. They also strongly recommend that this group of men discontinue CYC and thalidomide.

Pregnant women are strongly recommended to discontinue methotrexate, leflunomide (with cholestyramine washout if there are detectable serum levels of its metabolite prior to pregnancy or as soon as it is confirmed), MMF, CYC, and thalidomide within 3 months prior to conception, and they strongly recommend HCQ (in women with SLE), azathioprine/6‐mercaptopurine, colchicine, or sulfasalazine for use throughout pregnancy. They strongly recommend a combination of low‐dose aspirin and prophylactic‐dose heparin for pregnant women with obstetric APS, along with low‐dose aspirin and therapeutic‐dose heparin for women with thrombotic APS throughout pregnancy and postpartum. However, for women with SLE and those who test positive for aPL but do not meet criteria for obstetric or thrombotic APS, the authors conditionally recommend low-dose aspirin starting in the first trimester.

The guideline suggests that women with RMD should be encouraged to breastfeed if they are willing and able; they also suggest that disease control be maintained through lactation‐compatible medications and that the risks and benefits be reviewed on a patient-by-patient basis. Treatment with HCQ, colchicine, sulfasalazine, rituximab, and all tumor necrosis factor inhibitors are strongly recommended as being compatible with breastfeeding, and they strongly recommend against using CYC, leflunomide, MMF, and thalidomide while breastfeeding.

The authors acknowledged the limitations of their guideline, including the literature review being conducted on studies involving adults and an “inability to include recommendations for uncommon but important clinical situations,” including those involving transgender patients and hormonal therapies.

The authors reported numerous potential conflicts of interest, including receiving research support, consulting fees, speaking fees, and honoraria from various pharmaceutical companies.

SOURCE: Sammaritano LR et al. Arthritis Rheumatol. 2020 Feb 23. doi: 10.1002/art.41191.

The U.S. Preventive Services Task Force has deemed the current evidence “insufficient” to make a recommendation in regard to screening for cognitive impairment in adults aged 65 years or older.

“More research is needed on the effect of screening and early detection of cognitive impairment on important patient, caregiver, and societal outcomes, including decision making, advance planning, and caregiver outcomes,” wrote lead author Douglas K. Owens, MD, of Stanford (Calif.) University and fellow members of the task force. The statement was published in JAMA.

To update a 2014 recommendation from the USPSTF, which also found insufficient evidence to properly assess cognitive screening’s benefits and harms, the task force commissioned a systematic review of studies applicable to community-dwelling older adults who are not exhibiting signs or symptoms of cognitive impairment. For their statement, “cognitive impairment” is defined as mild cognitive impairment and mild to moderate dementia.

Ultimately, they determined several factors that limited the overall evidence, including the short duration of most trials and the heterogenous nature of interventions and inconsistencies in outcomes reported. Any evidence that suggested improvements was mostly applicable to patients with moderate dementia, meaning “its applicability to a screen-detected population is uncertain.”
 

Updating 2014 recommendations

Their statement was based on an evidence report, also published in JAMA, in which a team of researchers reviewed 287 studies that included more than 285,000 older adults; 92 of the studies were newly identified, while the other 195 were carried forward from the 2014 recommendation’s review. The researchers sought the answers to five key questions, carrying over the framework from the previous review.

“Despite the accumulation of new data, the conclusions for these key questions are essentially unchanged from the prior review,” wrote lead author Carrie D. Patnode, PhD, of the Kaiser Permanente Center for Health Research in Portland, Ore., and coauthors.

Of the questions – which concerned the accuracy of screening instruments; the harms of screening; the harms of interventions; and if screening or interventions improved decision making or outcomes for the patient, family/caregiver, or society – moderate evidence was found to support the accuracy of the instruments, treatment with acetylcholinesterase inhibitors and memantine for patients with moderate dementia, and psychoeducation interventions for caregivers of patients with moderate dementia. At the same time, there was moderate evidence of adverse effects from acetylcholinesterase inhibitors and memantine in patients with moderate dementia.

“I think, eventually, there will be sufficient evidence to justify screening, once we have what I call a tiered approach,” Marwan Sabbagh, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said in an interview. “The very near future will include blood tests for Alzheimer’s, or PET scans, or genetics, or something else. Right now, the cognitive screens lack the specificity and sensitivity, and the secondary screening infrastructure that would improve the accuracy doesn’t exist yet.

“I think this is a ‘not now,’ ” he added, “but I wouldn’t say ‘not ever.’ ”

Dr. Patnode and coauthors noted specific limitations in the evidence, including a lack of studies on how screening for and treating cognitive impairment affects decision making. In addition, details like quality of life and institutionalization were inconsistently reported, and “consistent and standardized reporting of results according to meaningful thresholds of clinical significance” would have been valuable across all measures.
 

Clinical implications

The implications of this report’s conclusions are substantial, especially as the rising prevalence of mild cognitive impairment and dementia becomes a worldwide concern, wrote Ronald C. Petersen, PhD, MD, of the Mayo Clinic in Rochester, Minn., and Kristine Yaffe, MD, of the University of California, San Francisco, in an accompanying editorial.

Though the data does not explicitly support screening, Dr. Petersen and Dr. Yaffe noted that it still may have benefits. An estimated 10% of cognitive impairment is caused by at least somewhat reversible causes, and screening could also be used to improve care in medical problems that are worsened by cognitive impairment. To find the true value of these efforts, they wrote, researchers need to design and execute additional clinical trials that “answer many of the important questions surrounding screening and treatment of cognitive impairment.”

“The absence of evidence for benefit may lead to inaction,” they added, noting that clinicians screening should still consider the value of screening on a case-by-case basis in order to keep up with the impact of new disease-modifying therapies for certain neurodegenerative diseases.

All members of the USPSTF received travel reimbursement and an honorarium for participating in meetings. One member reported receiving grants and personal fees from Healthwise. The study was funded by the Department of Health & Human Services. One of the authors reported receiving grants from the National Institutes of Health and the Food and Drug Administration. Dr. Petersen and Dr. Yaffe reported consulting for, and receiving funding from, various pharmaceutical companies, foundations, and government organizations.

SOURCES: Owens DK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0435; Patnode CD et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2019.22258.

The U.S. Preventive Services Task Force has deemed the current evidence “insufficient” to make a recommendation in regard to screening for cognitive impairment in adults aged 65 years or older.

“More research is needed on the effect of screening and early detection of cognitive impairment on important patient, caregiver, and societal outcomes, including decision making, advance planning, and caregiver outcomes,” wrote lead author Douglas K. Owens, MD, of Stanford (Calif.) University and fellow members of the task force. The statement was published in JAMA.

To update a 2014 recommendation from the USPSTF, which also found insufficient evidence to properly assess cognitive screening’s benefits and harms, the task force commissioned a systematic review of studies applicable to community-dwelling older adults who are not exhibiting signs or symptoms of cognitive impairment. For their statement, “cognitive impairment” is defined as mild cognitive impairment and mild to moderate dementia.

Ultimately, they determined several factors that limited the overall evidence, including the short duration of most trials and the heterogenous nature of interventions and inconsistencies in outcomes reported. Any evidence that suggested improvements was mostly applicable to patients with moderate dementia, meaning “its applicability to a screen-detected population is uncertain.”
 

Updating 2014 recommendations

Their statement was based on an evidence report, also published in JAMA, in which a team of researchers reviewed 287 studies that included more than 285,000 older adults; 92 of the studies were newly identified, while the other 195 were carried forward from the 2014 recommendation’s review. The researchers sought the answers to five key questions, carrying over the framework from the previous review.

“Despite the accumulation of new data, the conclusions for these key questions are essentially unchanged from the prior review,” wrote lead author Carrie D. Patnode, PhD, of the Kaiser Permanente Center for Health Research in Portland, Ore., and coauthors.

Of the questions – which concerned the accuracy of screening instruments; the harms of screening; the harms of interventions; and if screening or interventions improved decision making or outcomes for the patient, family/caregiver, or society – moderate evidence was found to support the accuracy of the instruments, treatment with acetylcholinesterase inhibitors and memantine for patients with moderate dementia, and psychoeducation interventions for caregivers of patients with moderate dementia. At the same time, there was moderate evidence of adverse effects from acetylcholinesterase inhibitors and memantine in patients with moderate dementia.

“I think, eventually, there will be sufficient evidence to justify screening, once we have what I call a tiered approach,” Marwan Sabbagh, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said in an interview. “The very near future will include blood tests for Alzheimer’s, or PET scans, or genetics, or something else. Right now, the cognitive screens lack the specificity and sensitivity, and the secondary screening infrastructure that would improve the accuracy doesn’t exist yet.

“I think this is a ‘not now,’ ” he added, “but I wouldn’t say ‘not ever.’ ”

Dr. Patnode and coauthors noted specific limitations in the evidence, including a lack of studies on how screening for and treating cognitive impairment affects decision making. In addition, details like quality of life and institutionalization were inconsistently reported, and “consistent and standardized reporting of results according to meaningful thresholds of clinical significance” would have been valuable across all measures.
 

Clinical implications

The implications of this report’s conclusions are substantial, especially as the rising prevalence of mild cognitive impairment and dementia becomes a worldwide concern, wrote Ronald C. Petersen, PhD, MD, of the Mayo Clinic in Rochester, Minn., and Kristine Yaffe, MD, of the University of California, San Francisco, in an accompanying editorial.

Though the data does not explicitly support screening, Dr. Petersen and Dr. Yaffe noted that it still may have benefits. An estimated 10% of cognitive impairment is caused by at least somewhat reversible causes, and screening could also be used to improve care in medical problems that are worsened by cognitive impairment. To find the true value of these efforts, they wrote, researchers need to design and execute additional clinical trials that “answer many of the important questions surrounding screening and treatment of cognitive impairment.”

“The absence of evidence for benefit may lead to inaction,” they added, noting that clinicians screening should still consider the value of screening on a case-by-case basis in order to keep up with the impact of new disease-modifying therapies for certain neurodegenerative diseases.

All members of the USPSTF received travel reimbursement and an honorarium for participating in meetings. One member reported receiving grants and personal fees from Healthwise. The study was funded by the Department of Health & Human Services. One of the authors reported receiving grants from the National Institutes of Health and the Food and Drug Administration. Dr. Petersen and Dr. Yaffe reported consulting for, and receiving funding from, various pharmaceutical companies, foundations, and government organizations.

SOURCES: Owens DK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0435; Patnode CD et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2019.22258.

The U.S. Preventive Services Task Force has deemed the current evidence “insufficient” to make a recommendation in regard to screening for cognitive impairment in adults aged 65 years or older.

“More research is needed on the effect of screening and early detection of cognitive impairment on important patient, caregiver, and societal outcomes, including decision making, advance planning, and caregiver outcomes,” wrote lead author Douglas K. Owens, MD, of Stanford (Calif.) University and fellow members of the task force. The statement was published in JAMA.

To update a 2014 recommendation from the USPSTF, which also found insufficient evidence to properly assess cognitive screening’s benefits and harms, the task force commissioned a systematic review of studies applicable to community-dwelling older adults who are not exhibiting signs or symptoms of cognitive impairment. For their statement, “cognitive impairment” is defined as mild cognitive impairment and mild to moderate dementia.

Ultimately, they determined several factors that limited the overall evidence, including the short duration of most trials and the heterogenous nature of interventions and inconsistencies in outcomes reported. Any evidence that suggested improvements was mostly applicable to patients with moderate dementia, meaning “its applicability to a screen-detected population is uncertain.”
 

Updating 2014 recommendations

Their statement was based on an evidence report, also published in JAMA, in which a team of researchers reviewed 287 studies that included more than 285,000 older adults; 92 of the studies were newly identified, while the other 195 were carried forward from the 2014 recommendation’s review. The researchers sought the answers to five key questions, carrying over the framework from the previous review.

“Despite the accumulation of new data, the conclusions for these key questions are essentially unchanged from the prior review,” wrote lead author Carrie D. Patnode, PhD, of the Kaiser Permanente Center for Health Research in Portland, Ore., and coauthors.

Of the questions – which concerned the accuracy of screening instruments; the harms of screening; the harms of interventions; and if screening or interventions improved decision making or outcomes for the patient, family/caregiver, or society – moderate evidence was found to support the accuracy of the instruments, treatment with acetylcholinesterase inhibitors and memantine for patients with moderate dementia, and psychoeducation interventions for caregivers of patients with moderate dementia. At the same time, there was moderate evidence of adverse effects from acetylcholinesterase inhibitors and memantine in patients with moderate dementia.

“I think, eventually, there will be sufficient evidence to justify screening, once we have what I call a tiered approach,” Marwan Sabbagh, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, said in an interview. “The very near future will include blood tests for Alzheimer’s, or PET scans, or genetics, or something else. Right now, the cognitive screens lack the specificity and sensitivity, and the secondary screening infrastructure that would improve the accuracy doesn’t exist yet.

“I think this is a ‘not now,’ ” he added, “but I wouldn’t say ‘not ever.’ ”

Dr. Patnode and coauthors noted specific limitations in the evidence, including a lack of studies on how screening for and treating cognitive impairment affects decision making. In addition, details like quality of life and institutionalization were inconsistently reported, and “consistent and standardized reporting of results according to meaningful thresholds of clinical significance” would have been valuable across all measures.
 

Clinical implications

The implications of this report’s conclusions are substantial, especially as the rising prevalence of mild cognitive impairment and dementia becomes a worldwide concern, wrote Ronald C. Petersen, PhD, MD, of the Mayo Clinic in Rochester, Minn., and Kristine Yaffe, MD, of the University of California, San Francisco, in an accompanying editorial.

Though the data does not explicitly support screening, Dr. Petersen and Dr. Yaffe noted that it still may have benefits. An estimated 10% of cognitive impairment is caused by at least somewhat reversible causes, and screening could also be used to improve care in medical problems that are worsened by cognitive impairment. To find the true value of these efforts, they wrote, researchers need to design and execute additional clinical trials that “answer many of the important questions surrounding screening and treatment of cognitive impairment.”

“The absence of evidence for benefit may lead to inaction,” they added, noting that clinicians screening should still consider the value of screening on a case-by-case basis in order to keep up with the impact of new disease-modifying therapies for certain neurodegenerative diseases.

All members of the USPSTF received travel reimbursement and an honorarium for participating in meetings. One member reported receiving grants and personal fees from Healthwise. The study was funded by the Department of Health & Human Services. One of the authors reported receiving grants from the National Institutes of Health and the Food and Drug Administration. Dr. Petersen and Dr. Yaffe reported consulting for, and receiving funding from, various pharmaceutical companies, foundations, and government organizations.

SOURCES: Owens DK et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2020.0435; Patnode CD et al. JAMA. 2020 Feb 25. doi: 10.1001/jama.2019.22258.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has determined modifiable and nonmodifiable factors that can help identify patients with axial spondyloarthritis who are both likely and unlikely to respond to anti–tumor necrosis factor (TNF)–alpha therapy.

Courtesy Dr. Gary J. Macfarlane

“[This study] emphasizes that examination of predictors of nonresponse to pharmacologic therapy in inflammatory arthritis must consider the importance of socioeconomic factors,” wrote Gary J. Macfarlane, MBChB, PhD, of the University of Aberdeen (Scotland) and coauthors. The study was published in Rheumatology.

To identify common factors related to anti–TNF-alpha therapy response, the researchers launched a prospective cohort study of 335 patients with axial spondyloarthritis from the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis (BSRBR-AS) who were naive to biologic therapy. Responses to therapy were assessed through various means, including meeting Assessment of Spondyloarthritis International Society (ASAS) improvement criteria, exhibiting clinically important improvement (1.1 points or more) in Ankylosing Spondylitis Disease Activity Score (ASDAS), or going from a high or very high ASDAS disease state (score of 2.1 or higher) to a moderate or inactive state (score less than 2.1).

All patients also filled out questionnaires at each follow-up on socioeconomic factors, lifestyle factors, and quality of life. Of the 335 participants, 69% were male. They had a median age of 47 years, and about half were employed full time.

At first follow-up – which occurred at a median of 14 weeks – 175 participants (52%) met ASAS20 response criteria and 111 (33%) met ASAS40 response criteria. Of the 261 participants eligible for ASDAS evaluation, 122 (47%) met the criteria for a clinically important ASDAS reduction. Of the 249 participants who had a high or very high disease state at baseline, 87 (35%) were classified as having moderate or inactive disease at follow-up.

Factors that predicted a lack of response across measures included adverse socioeconomic factors, fewer years of education, and not working full time. Clinical and patient-reported factors also associated with a lack of response included comorbidities and poor mental health. The ASDAS models proved best at predicting those unlikely to meet response criteria, with a negative predictive value of 77%.

The study was supported by the British Society for Rheumatology, which receives funding for the BSRBR-AS from Pfizer, AbbVie, and UCB. The authors reported having no conflicts of interest.

SOURCE: Macfarlane GJ et al. Rheumatology. 2020 Jan 28. doi: 10.1093/rheumatology/kez657.

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

A new study has found an elevated risk of some adverse events in patients treated with low-dose methotrexate, compared with patients treated with placebo.

“The data presented here provide an important source of new evidence to improve the monitoring guidelines and safe prescribing of LD-MTX [low-dose methotrexate],” wrote Daniel H. Solomon, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and coauthors. The study was published in Annals of Internal Medicine.

To determine the rates of adverse events (AEs) among LD-MTX users, along with assessing the risks of certain predefined AEs, the researchers enrolled 6,158 patients in the Cardiovascular Inflammation Reduction Trial (CIRT) and randomized 4,786 of those patients to two groups: those receiving LD-MTX (n = 2,391) and those receiving placebo (n = 2,395). The median dose was 15 mg per week, and median follow-up was 23 months. All participants in CIRT had a history of cardiovascular disease, along with diabetes or metabolic syndrome. Just over 81% of the participants were male, and nearly 85% were white. Their median age was nearly 66 years.

Of the participants in the LD-MTX group, 2,156 (90.2%) had an AE and 2,080 (87.0%) had an AE of interest, which included infectious, hematologic, pulmonary, hepatic, cancerous, and gastrointestinal AEs. Of the participants in the placebo group, 2,076 (86.7%) had an AE and 1,951 (81.5%) had an AE of interest. As such, the relative rate of an AE of interest was 17% higher in the LD-MTX group (hazard ratio, 1.17; 95% confidence interval, 1.10-1.25).

In regard to specific types of AEs, the rates of gastrointestinal (HR, 1.23; 95% CI, 1.03-1.47), pulmonary (HR, 1.42; 95% CI, 1.14-1.77), infectious (HR, 1.15; 95% CI, 1.01-1.30) and hematologic (HR, 1.22; 95% CI, 1.11-1.34) were higher for participants in the LD-MTX group. Five cases of cirrhosis were found in the LD-MTX group, compared with none in the placebo group; none of the patients with cirrhosis had severe liver test abnormalities before their diagnosis. While the risk of cancer overall was not elevated in the LD-MTX group, 53 participants in that group developed skin cancer, compared with 26 in the placebo group (HR, 2.04; 95% CI, 1.28-3.26). Renal AEs were among the few that decreased in LD-MTX users (HR, 0.85; 95% CI, 0.78-0.93).

“Methotrexate has become the standard of care for RA patients,” Dr. Solomon said in an interview, “and because it worked so well, we accepted it without large placebo-controlled trials and without a precise understanding of the risk factors for AEs. Until this study, our evidence basis for the side-effect profile was relatively weak.

“We had a limited data set but decades of experience,” he added. “Now we have better evidence, for example, that methotrexate is associated with elevations in liver function tests. We even found five cases of cirrhosis. And the people who developed cirrhosis didn’t have severe test abnormalities; just minor ones over many months. So now we have a better understanding of the potential impact of minor, yet chronic abnormalities.”

Dr. Solomon and coauthors acknowledged their study’s limitations, including CIRT not including patients with systemic rheumatic disease and the possibility that participants did not report AEs that occurred in between routine study visits. In addition, although the median follow-up of nearly 2 years was longer than in other LD-MTX trials, they noted that “it may still be too short to observe some AEs that require long-term exposure.”

Dr. Solomon and colleagues should be commended for undertaking a long-awaited randomized, placebo-controlled trial that adds much-needed insight into how and when to monitor patients being treated with MTX, Vivian P. Bykerk, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York, wrote in an editorial (Ann Intern Med. 2020 Feb 17. doi: 10.7326/M20-0435).

Dr. Bykerk noted that although the results may not be applicable to patients with RA and other inflammatory arthritides who are treated with MTX – RA patients in particular are younger, more often female, have lower rates of diabetes, and usually receive higher doses than those used in CIRT — the risk estimates from the CIRT study are “largely congruent with those expected in MTX-treated patients with rheumatic diseases.”

Regardless, she emphasized that this is a step in a much-needed direction, reminding physicians that “MTX use has inherent risks” and that its AEs, although infrequent, are clinically serious.

The National Institutes of Health funded the study. Various authors reported receiving grants from the National Heart, Lung, and Blood Institute, along with grants, research support, and personal fees from numerous pharmaceutical companies before and during the study. Dr. Bykerk reported receiving personal fees, grants, and nonfinancial support from pharmaceutical companies, foundations, and the NIH.

SOURCE: Solomon DH et al. Ann Intern Med. 2020 Feb 17. doi: 10.7326/M19-3369.

A new study has found that patients with atrial fibrillation (AF) who take oral anticoagulants and then suffer from lower GI bleeding have a much higher risk of being diagnosed with colorectal cancer.

“Our data indicate that lower GI bleeding in these patients should not be dismissed as a mere consequence of anticoagulation treatment,” wrote Peter Vibe Rasmussen, MD, of the University of Copenhagen in Denmark and his coauthors, adding that “timely examination could potentially provide early detection of malignant colorectal lesions.” The study was published in the European Heart Journal.

To determine whether being treated with oral anticoagulants (OACs) and subsequently undergoing GI bleeding indicates colorectal cancer, the researchers examined data from 125,418 Danish AF patients gathered from a nationwide registry. Their median age was 73 years old, and 58% (n = 73,271) were males.

Over a 3-year follow-up period, 2,576 cases of lower GI bleeding were identified; 140 of those cases led to a diagnosis of colorectal cancer within a year. The absolute 1-year risk of colorectal cancer after bleeding was 8.1% (95% confidence interval, 6.1-10.6%) in patients aged 76-80 and 3.7% (95% CI, 2.2-6.2%) in patients 65 years old or younger.

All age groups had a higher risk of colorectal cancer after bleeding, compared with patients without bleeding. Patients 65 or younger had a risk ratio of 24.2 (95% CI, 14.5-40.4) while patients over 85 had a risk ratio of 12.3 (95% CI, 7.9-19.0).

The authors acknowledged their study’s limitations, including a lack of information regarding certain risk factors, such as alcohol consumption, dietary habits, and obesity. In addition, they noted that the absolute risk of colorectal cancer in patients without bleeding is likely underdiagnosed, as “patients without GI bleeding are less likely to undergo diagnostic procedures.”

Two of the authors are employees at Bristol-Myers Squibb and Pfizer, respectively. Six additional authors reported receiving grants, speaker honoraria and consulting fees from various pharmaceutical companies. The remaining authors reported no conflicts of interest.

SOURCE: Rasmussen PV et al. Eur Heart J. 2020 Feb 7. doi: 10.1093/eurheartj/ehz964.

A new study has found that patients with atrial fibrillation (AF) who take oral anticoagulants and then suffer from lower GI bleeding have a much higher risk of being diagnosed with colorectal cancer.

“Our data indicate that lower GI bleeding in these patients should not be dismissed as a mere consequence of anticoagulation treatment,” wrote Peter Vibe Rasmussen, MD, of the University of Copenhagen in Denmark and his coauthors, adding that “timely examination could potentially provide early detection of malignant colorectal lesions.” The study was published in the European Heart Journal.

To determine whether being treated with oral anticoagulants (OACs) and subsequently undergoing GI bleeding indicates colorectal cancer, the researchers examined data from 125,418 Danish AF patients gathered from a nationwide registry. Their median age was 73 years old, and 58% (n = 73,271) were males.

Over a 3-year follow-up period, 2,576 cases of lower GI bleeding were identified; 140 of those cases led to a diagnosis of colorectal cancer within a year. The absolute 1-year risk of colorectal cancer after bleeding was 8.1% (95% confidence interval, 6.1-10.6%) in patients aged 76-80 and 3.7% (95% CI, 2.2-6.2%) in patients 65 years old or younger.

All age groups had a higher risk of colorectal cancer after bleeding, compared with patients without bleeding. Patients 65 or younger had a risk ratio of 24.2 (95% CI, 14.5-40.4) while patients over 85 had a risk ratio of 12.3 (95% CI, 7.9-19.0).

The authors acknowledged their study’s limitations, including a lack of information regarding certain risk factors, such as alcohol consumption, dietary habits, and obesity. In addition, they noted that the absolute risk of colorectal cancer in patients without bleeding is likely underdiagnosed, as “patients without GI bleeding are less likely to undergo diagnostic procedures.”

Two of the authors are employees at Bristol-Myers Squibb and Pfizer, respectively. Six additional authors reported receiving grants, speaker honoraria and consulting fees from various pharmaceutical companies. The remaining authors reported no conflicts of interest.

SOURCE: Rasmussen PV et al. Eur Heart J. 2020 Feb 7. doi: 10.1093/eurheartj/ehz964.

A new study has found that patients with atrial fibrillation (AF) who take oral anticoagulants and then suffer from lower GI bleeding have a much higher risk of being diagnosed with colorectal cancer.

“Our data indicate that lower GI bleeding in these patients should not be dismissed as a mere consequence of anticoagulation treatment,” wrote Peter Vibe Rasmussen, MD, of the University of Copenhagen in Denmark and his coauthors, adding that “timely examination could potentially provide early detection of malignant colorectal lesions.” The study was published in the European Heart Journal.

To determine whether being treated with oral anticoagulants (OACs) and subsequently undergoing GI bleeding indicates colorectal cancer, the researchers examined data from 125,418 Danish AF patients gathered from a nationwide registry. Their median age was 73 years old, and 58% (n = 73,271) were males.

Over a 3-year follow-up period, 2,576 cases of lower GI bleeding were identified; 140 of those cases led to a diagnosis of colorectal cancer within a year. The absolute 1-year risk of colorectal cancer after bleeding was 8.1% (95% confidence interval, 6.1-10.6%) in patients aged 76-80 and 3.7% (95% CI, 2.2-6.2%) in patients 65 years old or younger.

All age groups had a higher risk of colorectal cancer after bleeding, compared with patients without bleeding. Patients 65 or younger had a risk ratio of 24.2 (95% CI, 14.5-40.4) while patients over 85 had a risk ratio of 12.3 (95% CI, 7.9-19.0).

The authors acknowledged their study’s limitations, including a lack of information regarding certain risk factors, such as alcohol consumption, dietary habits, and obesity. In addition, they noted that the absolute risk of colorectal cancer in patients without bleeding is likely underdiagnosed, as “patients without GI bleeding are less likely to undergo diagnostic procedures.”

Two of the authors are employees at Bristol-Myers Squibb and Pfizer, respectively. Six additional authors reported receiving grants, speaker honoraria and consulting fees from various pharmaceutical companies. The remaining authors reported no conflicts of interest.

SOURCE: Rasmussen PV et al. Eur Heart J. 2020 Feb 7. doi: 10.1093/eurheartj/ehz964.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

England’s ban on smoking in cars carrying children led to a 72% relative reduction in the percentage of children self-reporting exposure to tobacco smoke in cars.

“Given children’s known vulnerability to secondhand smoke, reductions in exposure will probably result in improved health,” wrote Anthony A. Laverty, PhD, of Imperial College London and coauthors. Their findings were published in Thorax.

To determine the impact of a 2015 ban on smoking in cars carrying children in England and a 2016 ban in Scotland, the researchers analyzed survey data from 2012, 2014, and 2016 for each of the two countries. In England, children aged 13-15 years were asked, “In the past year, how often were you in a car with somebody smoking?” In Scotland, they were asked, “Are you regularly exposed to other people’s tobacco smoke in any of these places?” with cars/vehicles being one of the options.

Overall, 15,318 responses were received in England and 822 were received in Scotland. In England, self-reported regular exposure to smoke in cars was 6% in 2012, 6% in 2014 and 2% in 2016. In Scotland, it was 3% in 2012, 2% in 2014 and 1% in 2016. From 2014-2016 in England, implementation of the smoke-free policy was associated with a 4% absolute reduction – or a 72% relative reduction – in the percentage of children self-reporting exposure.

The authors acknowledged their study’s limitations, including exposure being based on self-reporting alone and the analyses using only three data points. “Future analyses with more data are recommended,” they wrote, “and may provide discrepant results.”

The study was funded by the National Institute for Health Research School for Public Health Research. One author was funded by the Medical Research Council on a clinician scientist fellowship. The others reported no potential conflicts of interest.

SOURCE: Laverty AA et al. Thorax. 2020 Jan 27. doi: 10.1136/thoraxjnl-2019-213998.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

A new study of claims-based data has found that the incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in most states.

Dr. George Kubica/CDC

To assess the NTM lung disease burden on a national level, Kevin L. Winthrop, MD, of Oregon Health & Science University, Portland, and associates analyzed patient data from a U.S. managed care claims database between 2008 and 2015. Their findings were published in the Annals of the American Thoracic Society.

A case of NTM lung disease was defined as a patient with at least two medical claims with the disease’s diagnostic codes – 031.0 and A31.0 – that were at least 30 days apart. Of the 74,984,596 beneficiaries in the database, 9,476 met the case definition for NTM lung disease; 69% (n = 6,530) were women.

From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval, 2.88-3.40) to 4.73 (95% CI, 4.43-5.05) per 100,000 person-years, with the average rate of yearly change being +5.2% (95% CI, 4.0%-6.4%; P less than .01).The annual prevalence increased from 6.78 (95% CI, 6.45-7.14) to 11.70 (95% CI, 11.26-12.16) per 100,000 persons, with the average rate of yearly change being +7.5% (95% CI, 6.7-8.2%; P less than .01).

The majority of NTM lung disease in the United States is caused by Mycobacterium avium complex (17), although other species such as M. abscessus, M. kansasii, M. xenopi, and others contribute to this disease burden.

“It’s a classic chicken-or-egg scenario,” said Sachin Gupta, MD, a pulmonologist in San Francisco, in regard to the rising numbers. “Increased awareness of NTM lung disease is, in part, why we’re seeing prevalence and incidence go up. And yet the disease itself may also be growing in clusters and pockets, as the data show, in various places across the nation.

“The worrisome aspect here,” he added, “is that future studies will likely show that, as incidence is increasing, mortality is increasing as well. That speaks to the challenges with these bugs: Very hard to diagnose, very hard to treat.”

The authors acknowledged their study’s limitations, including the lack of microbiologic or radiographic confirmation of the NTM infection and the inherent shortcomings of claims data–based studies overall. They did note a previous report, however, that “claims-based case identification has a high positive predictive value of approximately 82% for NTM lung disease.”

The study was funded by Insmed; the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases; and the National Heart, Lung, and Blood Institute. The authors reported no conflicts of interest.

SOURCE: Winthrop KL et al. Ann Am Thorac Soc. 2019 Dec 13. doi: 10.1513/AnnalsATS.201804-236OC.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.