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Noninferiority endpoint not met between Xeljanz formulations for RA
An 11-mg, once-daily, modified-release formulation of the Janus kinase inhibitor Xeljanz (tofacitinib) did not meet a noninferiority of efficacy primary endpoint when compared against a 5-mg, immediate-release formulation of the drug taken twice daily in a phase 3, randomized trial of 209 Japanese patients with rheumatoid arthritis.
Although the modified-release formulation did not achieve noninferiority with the immediate-release dosing after 12 weeks, the number of patients who achieved a clinically meaningful outcome was similar in both groups, Yoshiya Tanaka, MD, PhD, and his colleagues reported online Aug. 17 in Rheumatology.
Noninferiority between the two formulations “was to be declared if the upper bound of the two-sided 95% [confidence interval] for the difference in [Disease Activity Score in 28 Joints–C-reactive protein] between treatment groups was less than 0.6,” they said. The difference in DAS28-CRP scores of 0.43 had a 95% CI upper bound of 0.69, demonstrating a lack of noninferiority.
The percentages of patients achieving 1.2 or more points improvement in DAS28-CRP were similar at 89% of patients on the modified-release tofacitinib and 85% of those on immediate-release tofacitinib. At baseline, patients in the study were on a stable dose of methotrexate at 6-16 mg/week (mean of about 9.5 mg/week) for 6 or more weeks.
About half of patients in both groups reported adverse events, and serious adverse events occurred in 4%-5%.
Pfizer funded the study.
SOURCE: Tanaka Y et al. Rheumatology (Oxford). 2018 Aug 17. doi: 10.1093/rheumatology/key250.
An 11-mg, once-daily, modified-release formulation of the Janus kinase inhibitor Xeljanz (tofacitinib) did not meet a noninferiority of efficacy primary endpoint when compared against a 5-mg, immediate-release formulation of the drug taken twice daily in a phase 3, randomized trial of 209 Japanese patients with rheumatoid arthritis.
Although the modified-release formulation did not achieve noninferiority with the immediate-release dosing after 12 weeks, the number of patients who achieved a clinically meaningful outcome was similar in both groups, Yoshiya Tanaka, MD, PhD, and his colleagues reported online Aug. 17 in Rheumatology.
Noninferiority between the two formulations “was to be declared if the upper bound of the two-sided 95% [confidence interval] for the difference in [Disease Activity Score in 28 Joints–C-reactive protein] between treatment groups was less than 0.6,” they said. The difference in DAS28-CRP scores of 0.43 had a 95% CI upper bound of 0.69, demonstrating a lack of noninferiority.
The percentages of patients achieving 1.2 or more points improvement in DAS28-CRP were similar at 89% of patients on the modified-release tofacitinib and 85% of those on immediate-release tofacitinib. At baseline, patients in the study were on a stable dose of methotrexate at 6-16 mg/week (mean of about 9.5 mg/week) for 6 or more weeks.
About half of patients in both groups reported adverse events, and serious adverse events occurred in 4%-5%.
Pfizer funded the study.
SOURCE: Tanaka Y et al. Rheumatology (Oxford). 2018 Aug 17. doi: 10.1093/rheumatology/key250.
An 11-mg, once-daily, modified-release formulation of the Janus kinase inhibitor Xeljanz (tofacitinib) did not meet a noninferiority of efficacy primary endpoint when compared against a 5-mg, immediate-release formulation of the drug taken twice daily in a phase 3, randomized trial of 209 Japanese patients with rheumatoid arthritis.
Although the modified-release formulation did not achieve noninferiority with the immediate-release dosing after 12 weeks, the number of patients who achieved a clinically meaningful outcome was similar in both groups, Yoshiya Tanaka, MD, PhD, and his colleagues reported online Aug. 17 in Rheumatology.
Noninferiority between the two formulations “was to be declared if the upper bound of the two-sided 95% [confidence interval] for the difference in [Disease Activity Score in 28 Joints–C-reactive protein] between treatment groups was less than 0.6,” they said. The difference in DAS28-CRP scores of 0.43 had a 95% CI upper bound of 0.69, demonstrating a lack of noninferiority.
The percentages of patients achieving 1.2 or more points improvement in DAS28-CRP were similar at 89% of patients on the modified-release tofacitinib and 85% of those on immediate-release tofacitinib. At baseline, patients in the study were on a stable dose of methotrexate at 6-16 mg/week (mean of about 9.5 mg/week) for 6 or more weeks.
About half of patients in both groups reported adverse events, and serious adverse events occurred in 4%-5%.
Pfizer funded the study.
SOURCE: Tanaka Y et al. Rheumatology (Oxford). 2018 Aug 17. doi: 10.1093/rheumatology/key250.
FROM RHEUMATOLOGY
RA seroconversion not associated with sustained drug-free remission
In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.
“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.
“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”
The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.
An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.
“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”
The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).
SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.
In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.
“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.
“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”
The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.
An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.
“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”
The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).
SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.
In patients with seropositive rheumatoid arthritis, seroconversion within the first year of treatment is not associated with long-term sustained drug-free remission (SDFR), according to results of a randomized, treat-to-target study of patients with early RA.
“The clinical significance of seroconversion in RA and especially its relationship with long-term SDFR, an approximation of disease ‘cure’ of RA, is a topic of major interest,” wrote Emma C. de Moel, of the department of rheumatology at Leiden (Netherlands) University Medical Center, and her coauthors.
“Previous studies found no association of seroconversion with remission or radiographic damage,” the investigators wrote in Annals of the Rheumatic Diseases. “We here investigated the association between seroconversion and ... SDFR and found no association.”
The study involved 381 patients with early RA (less than 2 years) from the IMPROVED trial who were treated with methotrexate and high-dose prednisone. At baseline and 12 months, 14 RA-associated autoantibodies were measured by ELISA, including anti-CCP2 and rheumatoid factor. Patients were monitored for long-term SDFR, defined as remission lasting longer than 1 year, beginning at any time, and persisting until the maximum follow-up of 5 years.
An association between seroconversion and SDFR was not found. At 12 months, 6 of 170 patients (3.5%) had seroconverted all autoantibodies to negative, and 2 of these 6 patients achieved SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved SDFR without seroconversion (P = .11). Additionally, neither the proportion of autoantibodies converted to negative nor relative decreases in autoantibody levels were associated with SDFR.
“It appears that seroconversion (as measured by current standards) does not identify a group of patients in ... true immunological remission, and is not superior to signals of low inflammatory load (e.g. by DAS 6) for predicting successful drug tapering,” the investigators concluded. “Future studies are needed to identify whether other immunological parameters such as the numbers or phenotype of circulating autoreactive B or T cells might be a better reflection of disease persistence and markers for immunological remission.”
The study was funded by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).
SOURCE: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: At 12 months, 6 of 170 seropositive patients (3.5%) had seroconverted, and 2 of these 6 patients achieved long-term SDFR, compared with 19 of 164 seropositive patients (11.6%) who achieved long-term SDFR without seroconversion (P = .11).
Study details: Baseline and 12-month serum autoantibody analysis of 381 RA patients from the IMPROVED trial; a randomized, treat-to-target study of patients with early RA (less than 2 years).
Disclosures: Funding was provided by ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA (MODIRA).
Source: de Moel EC et al. Ann Rheum Dis. 2018 Jul 25. doi: 10.1136/annrheumdis-2018-213823.
Fibromyalgia should be seen as one, not two disorders
The symptomatology and severity of fibromyalgia is virtually identical among people with primary and secondary forms of the disorder, researchers say, and the two should therefore be considered the same.
Currently, patients classified as having primary fibromyalgia have a defined set of pain, fatigue, cognitive, and psychological symptoms in the absence of a clinically important inflammatory disorder, while secondary fibromyalgia occurs in the context of a disease such as rheumatoid arthritis.
In research published online in the Journal of Rheumatology, investigators led by Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas in Wichita, sought to understand whether patients with primary and secondary diagnoses “had the same level of outcomes, symptoms, and characteristics” at different points across the polysymptomatic distress (PSD) scale, a measure to assess severity in fibromyalgia.
The PSD is calculated by combining two measurements used in fibromyalgia: the widespread pain index (WPI), which counts the number of painful regions in the body, and the somatic symptom scale (SSS), which measures fatigue, sleep, emotional and cognitive problems, and the extent of symptom reporting. Higher PSD scores correlate to worse outcomes, including for disability and health-related quality of life.
Dr. Wolfe and his colleagues compared records from 1,525 patients (mean age 57, 95% women) in the National Data Bank who were diagnosed with fibromyalgia only, with those from 12,037 people with rheumatoid arthritis (mean age 61, 82% women) and not evaluated for fibromyalgia. They also looked at data on fibromyalgia symptoms from a general population sample in Germany.
A total of 22% of the RA patients in the cohort met the criteria for a fibromyalgia diagnosis under current (2016) ACR criteria, while 53% of the patients in the primary fibromyalgia group and 2.0% of the general population sample did. Symptom magnitude and severity differed only slightly between the RA and fibromyalgia-only groups, the investigators found. Those without RA had a mean PSD score of 21.9 (of a possible 31) and those with RA and who met the fibromyalgia criteria had a mean score of 20.7.
The researchers found that the disease behaved similarly whether it occurred alone or with RA. Patients with higher PSD scores experienced worse outcomes across symptom domains regardless of RA status. When controlled for PSD, pain, patient global, and health-related quality of life, scores were similar between groups. However, disability scores and painful joint counts were slightly higher in the RA group.
“Fibromyalgia can exist whether or not there’s another disorder present,” Dr. Wolfe said in an interview, “but we don’t tend to think of it that way.” Clinicians, Dr. Wolfe said, “have to be able to identify [fibromyalgia] within other disorders. It can’t be only something that you find once you’ve ruled out everything else.”
Clinicians can look to PSD scores to inform management choices, the researchers said, instead of whether the fibromyalgia is considered primary or secondary.
Dr. Wolfe said that the current bifurcated concept of the disease also creates difficulties for research into fibromyalgia treatments. For example, using RA patients as a comparator group in a clinical trial is problematic because RA patients, as this study demonstrates, also have a substantial burden of fibromyalgia. And the use of so-called healthy controls in fibromyalgia studies is also a problem, Dr. Wolfe said.
“People say they’ve tried this drug or treatment in people with fibromyalgia and on normal controls. But there’s no such thing as normal controls for fibromyalgia. Does normal mean people with zero fatigue or pain? Or do we look at what’s normal among people who have multiple sclerosis or RA? If you’re going to test things in people with fibromyalgia, you never really have normal controls because it depends on where in this whole continuum you are.”
But what this new research also shows, he said, is that while up to now “you couldn’t easily study people with fibromyalgia [in other disorders], it doesn’t matter if you have RA or another disorder in addition to fibromyalgia. You get the full spectrum or severity regardless. The underlying disease wouldn’t affect your identification of the fibromyalgia symptoms.”
Dr. Wolfe and his colleagues described as a limitation of their study the lack of comparator groups besides RA patients. Secondary fibromyalgia is also commonly reported with osteoarthritis, they noted.
The study had no outside funding and investigators reported no conflicts of interest.
SOURCE: Wolfe F et al. J Rheumatol. 2018 Jul 15. doi: 10.3899/jrheum.180083.
The symptomatology and severity of fibromyalgia is virtually identical among people with primary and secondary forms of the disorder, researchers say, and the two should therefore be considered the same.
Currently, patients classified as having primary fibromyalgia have a defined set of pain, fatigue, cognitive, and psychological symptoms in the absence of a clinically important inflammatory disorder, while secondary fibromyalgia occurs in the context of a disease such as rheumatoid arthritis.
In research published online in the Journal of Rheumatology, investigators led by Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas in Wichita, sought to understand whether patients with primary and secondary diagnoses “had the same level of outcomes, symptoms, and characteristics” at different points across the polysymptomatic distress (PSD) scale, a measure to assess severity in fibromyalgia.
The PSD is calculated by combining two measurements used in fibromyalgia: the widespread pain index (WPI), which counts the number of painful regions in the body, and the somatic symptom scale (SSS), which measures fatigue, sleep, emotional and cognitive problems, and the extent of symptom reporting. Higher PSD scores correlate to worse outcomes, including for disability and health-related quality of life.
Dr. Wolfe and his colleagues compared records from 1,525 patients (mean age 57, 95% women) in the National Data Bank who were diagnosed with fibromyalgia only, with those from 12,037 people with rheumatoid arthritis (mean age 61, 82% women) and not evaluated for fibromyalgia. They also looked at data on fibromyalgia symptoms from a general population sample in Germany.
A total of 22% of the RA patients in the cohort met the criteria for a fibromyalgia diagnosis under current (2016) ACR criteria, while 53% of the patients in the primary fibromyalgia group and 2.0% of the general population sample did. Symptom magnitude and severity differed only slightly between the RA and fibromyalgia-only groups, the investigators found. Those without RA had a mean PSD score of 21.9 (of a possible 31) and those with RA and who met the fibromyalgia criteria had a mean score of 20.7.
The researchers found that the disease behaved similarly whether it occurred alone or with RA. Patients with higher PSD scores experienced worse outcomes across symptom domains regardless of RA status. When controlled for PSD, pain, patient global, and health-related quality of life, scores were similar between groups. However, disability scores and painful joint counts were slightly higher in the RA group.
“Fibromyalgia can exist whether or not there’s another disorder present,” Dr. Wolfe said in an interview, “but we don’t tend to think of it that way.” Clinicians, Dr. Wolfe said, “have to be able to identify [fibromyalgia] within other disorders. It can’t be only something that you find once you’ve ruled out everything else.”
Clinicians can look to PSD scores to inform management choices, the researchers said, instead of whether the fibromyalgia is considered primary or secondary.
Dr. Wolfe said that the current bifurcated concept of the disease also creates difficulties for research into fibromyalgia treatments. For example, using RA patients as a comparator group in a clinical trial is problematic because RA patients, as this study demonstrates, also have a substantial burden of fibromyalgia. And the use of so-called healthy controls in fibromyalgia studies is also a problem, Dr. Wolfe said.
“People say they’ve tried this drug or treatment in people with fibromyalgia and on normal controls. But there’s no such thing as normal controls for fibromyalgia. Does normal mean people with zero fatigue or pain? Or do we look at what’s normal among people who have multiple sclerosis or RA? If you’re going to test things in people with fibromyalgia, you never really have normal controls because it depends on where in this whole continuum you are.”
But what this new research also shows, he said, is that while up to now “you couldn’t easily study people with fibromyalgia [in other disorders], it doesn’t matter if you have RA or another disorder in addition to fibromyalgia. You get the full spectrum or severity regardless. The underlying disease wouldn’t affect your identification of the fibromyalgia symptoms.”
Dr. Wolfe and his colleagues described as a limitation of their study the lack of comparator groups besides RA patients. Secondary fibromyalgia is also commonly reported with osteoarthritis, they noted.
The study had no outside funding and investigators reported no conflicts of interest.
SOURCE: Wolfe F et al. J Rheumatol. 2018 Jul 15. doi: 10.3899/jrheum.180083.
The symptomatology and severity of fibromyalgia is virtually identical among people with primary and secondary forms of the disorder, researchers say, and the two should therefore be considered the same.
Currently, patients classified as having primary fibromyalgia have a defined set of pain, fatigue, cognitive, and psychological symptoms in the absence of a clinically important inflammatory disorder, while secondary fibromyalgia occurs in the context of a disease such as rheumatoid arthritis.
In research published online in the Journal of Rheumatology, investigators led by Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases and the University of Kansas in Wichita, sought to understand whether patients with primary and secondary diagnoses “had the same level of outcomes, symptoms, and characteristics” at different points across the polysymptomatic distress (PSD) scale, a measure to assess severity in fibromyalgia.
The PSD is calculated by combining two measurements used in fibromyalgia: the widespread pain index (WPI), which counts the number of painful regions in the body, and the somatic symptom scale (SSS), which measures fatigue, sleep, emotional and cognitive problems, and the extent of symptom reporting. Higher PSD scores correlate to worse outcomes, including for disability and health-related quality of life.
Dr. Wolfe and his colleagues compared records from 1,525 patients (mean age 57, 95% women) in the National Data Bank who were diagnosed with fibromyalgia only, with those from 12,037 people with rheumatoid arthritis (mean age 61, 82% women) and not evaluated for fibromyalgia. They also looked at data on fibromyalgia symptoms from a general population sample in Germany.
A total of 22% of the RA patients in the cohort met the criteria for a fibromyalgia diagnosis under current (2016) ACR criteria, while 53% of the patients in the primary fibromyalgia group and 2.0% of the general population sample did. Symptom magnitude and severity differed only slightly between the RA and fibromyalgia-only groups, the investigators found. Those without RA had a mean PSD score of 21.9 (of a possible 31) and those with RA and who met the fibromyalgia criteria had a mean score of 20.7.
The researchers found that the disease behaved similarly whether it occurred alone or with RA. Patients with higher PSD scores experienced worse outcomes across symptom domains regardless of RA status. When controlled for PSD, pain, patient global, and health-related quality of life, scores were similar between groups. However, disability scores and painful joint counts were slightly higher in the RA group.
“Fibromyalgia can exist whether or not there’s another disorder present,” Dr. Wolfe said in an interview, “but we don’t tend to think of it that way.” Clinicians, Dr. Wolfe said, “have to be able to identify [fibromyalgia] within other disorders. It can’t be only something that you find once you’ve ruled out everything else.”
Clinicians can look to PSD scores to inform management choices, the researchers said, instead of whether the fibromyalgia is considered primary or secondary.
Dr. Wolfe said that the current bifurcated concept of the disease also creates difficulties for research into fibromyalgia treatments. For example, using RA patients as a comparator group in a clinical trial is problematic because RA patients, as this study demonstrates, also have a substantial burden of fibromyalgia. And the use of so-called healthy controls in fibromyalgia studies is also a problem, Dr. Wolfe said.
“People say they’ve tried this drug or treatment in people with fibromyalgia and on normal controls. But there’s no such thing as normal controls for fibromyalgia. Does normal mean people with zero fatigue or pain? Or do we look at what’s normal among people who have multiple sclerosis or RA? If you’re going to test things in people with fibromyalgia, you never really have normal controls because it depends on where in this whole continuum you are.”
But what this new research also shows, he said, is that while up to now “you couldn’t easily study people with fibromyalgia [in other disorders], it doesn’t matter if you have RA or another disorder in addition to fibromyalgia. You get the full spectrum or severity regardless. The underlying disease wouldn’t affect your identification of the fibromyalgia symptoms.”
Dr. Wolfe and his colleagues described as a limitation of their study the lack of comparator groups besides RA patients. Secondary fibromyalgia is also commonly reported with osteoarthritis, they noted.
The study had no outside funding and investigators reported no conflicts of interest.
SOURCE: Wolfe F et al. J Rheumatol. 2018 Jul 15. doi: 10.3899/jrheum.180083.
FROM THE JOURNAL OF RHEUMATOLOGY
Key clinical point: Fibromyalgia behaves similarly whether it occurs alone or in the context of another disease.
Major finding: Patients with RA plus fibromyalgia had mean fibromyalgia severity scores of 21.9 while those with fibromyalgia alone had 20.7, and results were similar across 17 clinical variables measured in fibromyalgia.
Study details: Investigators compared records from 1,525 subjects with a diagnosis of fibromyalgia and another 12,037 with a diagnosis of RA.
Disclosures: The study had no outside funding and the investigators reported no conflicts of interest.
Source: Wolfe F et al. J Rheumatol. 2018 Jul 15. doi: 10.3899/jrheum.180083.
FDA announces plan for biosimilar innovation and competition
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Some of the actions include tools to enhance public information about the FDA’s evaluation of biosimilars, including more information about approved biological products in the Purple Book; exploring the potential for entering into new data sharing agreements with foreign regulators to facilitate the increased use of non–U.S.-licensed comparator products in certain studies to support a biosimilar application; releasing a series of videos that explain key concepts about biosimilar and interchangeable products; and requesting information from the public on additional policy steps the FDA should consider for enhancing the biosimilar program.
The FDA’s Biosimilar Action Plan is available here.
Glucocorticoids linked with surgical infections in RA patients
AMSTERDAM – Patients with rheumatoid arthritis who underwent elective knee or hip arthroplasty had a doubled rate of hospitalization for infection when they averaged more than 10 mg/day oral prednisone during the 3 months before surgery, based on a review of about 11,000 U.S. insurance claims.
“Limiting glucocorticoid exposure before surgery should be a focus of perioperative management,” Michael D. George, MD, said at the European Congress of Rheumatology. “Glucocorticoid use, especially greater than 10 mg/day, is associated with a greater risk of infection and hospital readmission,” said Dr. George, a rheumatologist at the University of Pennsylvania in Philadelphia.
The analysis also showed that treatment with any biologic drug – including abatacept (Orencia), rituximab (Rituxan), tocilizumab (Actemra), and any of several tumor necrosis factor (TNF) inhibitors – had a similar impact on both postsurgical infections requiring hospitalization and 30-day hospital readmissions.
The findings suggest “it’s more important to reduce glucocorticoids than biological drugs,” commented John D. Isaacs, MD, professor of clinical rheumatology at Newcastle University in Newcastle upon Tyne, England. “This is a really important question that has been very difficult to answer.”
Dr. George and his associates used data from patients with rheumatoid arthritis during 2006-2015 who underwent knee or hip arthroplasty and were in databases from Medicare, or MarketScan, which includes commercial insurers. This identified 11,021 RA patients on any of several biologic drugs before their surgery: 16% on abatacept, 4% on rituximab, 4% on tocilizumab, and the remaining 76% on a TNF inhibitor, either adalimumab (Humira), etanercept (Enbrel), or infliximab (Remicade). About 43% of all patients were on a glucocorticoid during the 3 months before surgery. Biologic use was defined as a minimum of one dose within 8 weeks of surgery, and at least three total dosages during the prior year, except for rituximab, which was at least one dose given 16 weeks before surgery and at least two doses during the prior year.
The rate of hospitalized infections ranged from 6.6% to 8.5% depending on the biologic drug used, and 30-day readmissions ranged from 4.8% to 6.8%. A third outcome the analysis assessed was prosthetic joint infection during 1-year follow-up, which was again similar across most of the biologics, except for patients on tocilizumab, who had prosthetic joint infections roughly threefold more often than the other patients. Although this was a statistically significant difference, Dr. George discounted the finding given the very small number of tocilizumab-treated patients who had these infections and said that any conclusion about tocilizumab’s effect on this outcome had to await data from more patients.
The glucocorticoid analysis divided patients into four subgroups: those not on a glucocorticoid, those on an average daily dosage of 5 mg/day prednisone or equivalent or less, patients on 6-10 mg/day prednisone, and those on more than 10 mg/day. In a propensity-weighted analysis, these three escalating levels of glucocorticoid use showed a dose-response relationship to the rates of both hospitalized infections and 30-day readmissions. At the highest level of glucocorticoid use, hospitalized infections occurred twice as often as in patients not on a glucocorticoid, and 30-day readmissions were more than 50% higher than in those not on an oral steroid, both statistically significant differences. For the outcome of 1-year prosthetic joint infections, the analysis again showed a dose-related link among glucocorticoid users, topping out with a greater than 50% increased rate among those on the highest glucocorticoid dosages when compared with nonusers, but this difference was not statistically significant.
The study was partially funded by Bristol-Myers Squibb, the company that markets abatacept. Dr. George has received research funding from Bristol-Myers Squibb, and some of his coauthors on the study are employees of the company.
SOURCE: George MD et al. EULAR 2018. Abstract OP0228.
AMSTERDAM – Patients with rheumatoid arthritis who underwent elective knee or hip arthroplasty had a doubled rate of hospitalization for infection when they averaged more than 10 mg/day oral prednisone during the 3 months before surgery, based on a review of about 11,000 U.S. insurance claims.
“Limiting glucocorticoid exposure before surgery should be a focus of perioperative management,” Michael D. George, MD, said at the European Congress of Rheumatology. “Glucocorticoid use, especially greater than 10 mg/day, is associated with a greater risk of infection and hospital readmission,” said Dr. George, a rheumatologist at the University of Pennsylvania in Philadelphia.
The analysis also showed that treatment with any biologic drug – including abatacept (Orencia), rituximab (Rituxan), tocilizumab (Actemra), and any of several tumor necrosis factor (TNF) inhibitors – had a similar impact on both postsurgical infections requiring hospitalization and 30-day hospital readmissions.
The findings suggest “it’s more important to reduce glucocorticoids than biological drugs,” commented John D. Isaacs, MD, professor of clinical rheumatology at Newcastle University in Newcastle upon Tyne, England. “This is a really important question that has been very difficult to answer.”
Dr. George and his associates used data from patients with rheumatoid arthritis during 2006-2015 who underwent knee or hip arthroplasty and were in databases from Medicare, or MarketScan, which includes commercial insurers. This identified 11,021 RA patients on any of several biologic drugs before their surgery: 16% on abatacept, 4% on rituximab, 4% on tocilizumab, and the remaining 76% on a TNF inhibitor, either adalimumab (Humira), etanercept (Enbrel), or infliximab (Remicade). About 43% of all patients were on a glucocorticoid during the 3 months before surgery. Biologic use was defined as a minimum of one dose within 8 weeks of surgery, and at least three total dosages during the prior year, except for rituximab, which was at least one dose given 16 weeks before surgery and at least two doses during the prior year.
The rate of hospitalized infections ranged from 6.6% to 8.5% depending on the biologic drug used, and 30-day readmissions ranged from 4.8% to 6.8%. A third outcome the analysis assessed was prosthetic joint infection during 1-year follow-up, which was again similar across most of the biologics, except for patients on tocilizumab, who had prosthetic joint infections roughly threefold more often than the other patients. Although this was a statistically significant difference, Dr. George discounted the finding given the very small number of tocilizumab-treated patients who had these infections and said that any conclusion about tocilizumab’s effect on this outcome had to await data from more patients.
The glucocorticoid analysis divided patients into four subgroups: those not on a glucocorticoid, those on an average daily dosage of 5 mg/day prednisone or equivalent or less, patients on 6-10 mg/day prednisone, and those on more than 10 mg/day. In a propensity-weighted analysis, these three escalating levels of glucocorticoid use showed a dose-response relationship to the rates of both hospitalized infections and 30-day readmissions. At the highest level of glucocorticoid use, hospitalized infections occurred twice as often as in patients not on a glucocorticoid, and 30-day readmissions were more than 50% higher than in those not on an oral steroid, both statistically significant differences. For the outcome of 1-year prosthetic joint infections, the analysis again showed a dose-related link among glucocorticoid users, topping out with a greater than 50% increased rate among those on the highest glucocorticoid dosages when compared with nonusers, but this difference was not statistically significant.
The study was partially funded by Bristol-Myers Squibb, the company that markets abatacept. Dr. George has received research funding from Bristol-Myers Squibb, and some of his coauthors on the study are employees of the company.
SOURCE: George MD et al. EULAR 2018. Abstract OP0228.
AMSTERDAM – Patients with rheumatoid arthritis who underwent elective knee or hip arthroplasty had a doubled rate of hospitalization for infection when they averaged more than 10 mg/day oral prednisone during the 3 months before surgery, based on a review of about 11,000 U.S. insurance claims.
“Limiting glucocorticoid exposure before surgery should be a focus of perioperative management,” Michael D. George, MD, said at the European Congress of Rheumatology. “Glucocorticoid use, especially greater than 10 mg/day, is associated with a greater risk of infection and hospital readmission,” said Dr. George, a rheumatologist at the University of Pennsylvania in Philadelphia.
The analysis also showed that treatment with any biologic drug – including abatacept (Orencia), rituximab (Rituxan), tocilizumab (Actemra), and any of several tumor necrosis factor (TNF) inhibitors – had a similar impact on both postsurgical infections requiring hospitalization and 30-day hospital readmissions.
The findings suggest “it’s more important to reduce glucocorticoids than biological drugs,” commented John D. Isaacs, MD, professor of clinical rheumatology at Newcastle University in Newcastle upon Tyne, England. “This is a really important question that has been very difficult to answer.”
Dr. George and his associates used data from patients with rheumatoid arthritis during 2006-2015 who underwent knee or hip arthroplasty and were in databases from Medicare, or MarketScan, which includes commercial insurers. This identified 11,021 RA patients on any of several biologic drugs before their surgery: 16% on abatacept, 4% on rituximab, 4% on tocilizumab, and the remaining 76% on a TNF inhibitor, either adalimumab (Humira), etanercept (Enbrel), or infliximab (Remicade). About 43% of all patients were on a glucocorticoid during the 3 months before surgery. Biologic use was defined as a minimum of one dose within 8 weeks of surgery, and at least three total dosages during the prior year, except for rituximab, which was at least one dose given 16 weeks before surgery and at least two doses during the prior year.
The rate of hospitalized infections ranged from 6.6% to 8.5% depending on the biologic drug used, and 30-day readmissions ranged from 4.8% to 6.8%. A third outcome the analysis assessed was prosthetic joint infection during 1-year follow-up, which was again similar across most of the biologics, except for patients on tocilizumab, who had prosthetic joint infections roughly threefold more often than the other patients. Although this was a statistically significant difference, Dr. George discounted the finding given the very small number of tocilizumab-treated patients who had these infections and said that any conclusion about tocilizumab’s effect on this outcome had to await data from more patients.
The glucocorticoid analysis divided patients into four subgroups: those not on a glucocorticoid, those on an average daily dosage of 5 mg/day prednisone or equivalent or less, patients on 6-10 mg/day prednisone, and those on more than 10 mg/day. In a propensity-weighted analysis, these three escalating levels of glucocorticoid use showed a dose-response relationship to the rates of both hospitalized infections and 30-day readmissions. At the highest level of glucocorticoid use, hospitalized infections occurred twice as often as in patients not on a glucocorticoid, and 30-day readmissions were more than 50% higher than in those not on an oral steroid, both statistically significant differences. For the outcome of 1-year prosthetic joint infections, the analysis again showed a dose-related link among glucocorticoid users, topping out with a greater than 50% increased rate among those on the highest glucocorticoid dosages when compared with nonusers, but this difference was not statistically significant.
The study was partially funded by Bristol-Myers Squibb, the company that markets abatacept. Dr. George has received research funding from Bristol-Myers Squibb, and some of his coauthors on the study are employees of the company.
SOURCE: George MD et al. EULAR 2018. Abstract OP0228.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point:
Major finding: RA patients on more than 10 mg/day prednisone had a more than twofold higher rate of postsurgical hospitalized infections.
Study details: Review of Medicare and MarketScan administrative claims data for 11,021 patients with rheumatoid arthritis who underwent joint surgery.
Disclosures: The study was partially funded by Bristol-Myers Squibb, the company that markets abatacept (Orencia). Dr. George has received research funding from Bristol-Myers Squibb, and some of his coauthors on the study are employees of the company.
Source: George MD et al. EULAR 2018. Abstract OP0228.
Biosimilar switch accepted by most rheumatic disease patients
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
LIVERPOOL, ENGLAND – , although the biosimilar they are being switched to may be important, according to data from three separate poster presentations at the British Society for Rheumatology annual conference.
Of 35 patients who expressed concerns about the switch, most (n = 27) were concerned about the efficacy of the biosimilar, with others were mainly concerned about safety (n = 5), side effects (n = 3), or other factors (n = 5).
“This is the population of patients we were worried about, because we had got them on a drug that had finally worked for them,” poster presenter Joanne Kitchen, MBChB, said in an interview.
“It’s hard enough to get on the biologic, and we were concerned about whether they would lose response. ... There wasn’t a lot of evidence about if they didn’t respond and we switched back, would it still work for them,” explained Dr. Kitchen, a consultant rheumatologist who works at the Royal Berkshire Hospital in Reading, England.
Biosimilar etanercept became available in the United Kingdom in April 2016, and many rheumatology centers had to make the switch to its use at the behest of their health trusts in a cost-saving effort. The switch at the Royal Berkshire occurred in August 2016, and Dr. Kitchen explained that prior to the switch, letters were sent out to inform patients, who were then seen in the clinic. There also was an understanding between the medical team and the patients that, if things did not work out, patients could switch back to the originator etanercept.
Between August 2016 and February 2017, 113 patients had switched to biosimilar etanercept for their rheumatoid arthritis (RA), spondyloarthritis, or psoriatic arthritis.
Although worsening joint pain or stiffness (n = 12) or increased fatigue (n = 4) were reported by some patients, the fact that 88% of those who responded to the survey in October 2017 were still taking the drug 6-12 months after initiation suggests that these side effects were minor or manageable. Adherence to medication was not checked, however, which might have been a factor in any flare ups.
Medication changes occurred for four patients who switched back to originator etanercept, three to an alternative biologic, and four who discontinued biologics.
Other adverse effects reported by patients were more painful injections (n = 5), infections (n = 2), and others incidents such as individual cases of rash and headache in the remainder.
“We know our biologic costs are incrementally increasing, but it’s still very hard for some patients to get onto these drugs,” Dr. Kitchen said. She hopes that with the cost-savings being made from the switch, it could help with negotiations to lower the threshold at which patients become eligible for biologic/biosimilar use, thus enabling more patients in need to be treated.
“I think these data have given confidence that patients can switch onto a biosimilar, and that the real-world experience matches what we’re seeing in trials,” Dr. Kitchen said. “We haven’t had a negative experience, and that’s what patients and we were worried about.”
In a separate poster presentation, Kavina Shah, MBBS, and her associates from Northwick Park Hospital, London, reported their experience of switching 115 patients with RA from etanercept to the biosimilar Benepali between January and June 2017.
They conducted a prospective study in which patients were offered an education session and then attended a clinic appointment set up to manage the switch. Patients were assessed by various objective and subjective means before and 4 months after the switch.
Dr. Shah and her associates found that 43% of patients were pleased with the switch. Part of the reason patients might have been happy with the switch was the easier mode of administration, they observed: “Patients commented on the easier technique and less manual dexterity required.”
However, almost a quarter (23%) of patients were not happy with the switch, with others being indifferent (7%) or unsure (8%).
Patients were also asked how they felt their RA was after the switch, and 75% responded that it was no different, 11% said it had improved, and 17% said it was worse.
The mean Disease Activity Score in 28 joints (DAS28) values were significantly lower in patients after the switch than before (2.66 vs. 2.97; P = .0019). “This could be explained by the lower levels of immunogenicity with Benepali,” Dr. Shah and her coauthors wrote on their poster. Alternatively, it could be an artifact introduced by lower rates of anxiety at follow-up, they said.
There were also statistically nonsignificant improvements in health assessment questionnaire (HAQ) and European Quality of Life-5 Dimensions (EQ-5D) scores.
Taken together, these findings are “reassuring,” Dr. Shah and her associates noted, and “should positively encourage clinicians and patients to switch to biosimilars in order to optimize the cost saving to the NHS.”
Not all biosimilar switches may go as smoothly as switching from TNF inhibitors, as Muhammad K. Nisar, MBBS, reported in another poster presentation at the conference. Dr. Nisar, a consultant rheumatologist for Luton (England) and Dunstable Hospital University Trust, reported his center’s experience of switching patients on rituximab (Rituxan) to biosimilar rituximab (Truxima).
Of 44 patients who were established on rituximab, 39 were eligible to make the switch. Four patients had stopped taking rituximab before the switch took place and one patient remained on the originator. As of October 2017, 24 (61.5%) of patients had actually made the switch.
“All were happy to switch after receiving a letter and having the opportunity to contact if necessary,” Dr. Nisar reported. “At group level there were no major differences in disease outcomes and 80% reported no issues.”
However, five (20%) patients developed a severe serum sickness reaction early on with loss of efficacy. This happened in the first week after the second dose of the biosimilar was given, Dr. Nisar explained. No obvious reason could be found, but two patients required emergency hospital treatment within 24 hours.
“Our experience of switching rituximab patients is certainly not as smooth as it was for infliximab or and etanercept,” Dr. Nisar said. While he said “they support routine switching from originator to biosimilar,” he noted that “close monitoring is required, certainly in the first week of dose administration.”
All authors had nothing to disclose.
SOURCES: Hoque T et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.296. Shah K et al. Rheumatology. 2018 Apr 25;57(Suppl. 3):key075.456. Nisar MK. Rheumatology. 2018 Apr 1;57(Suppl. 3):key075.516.
REPORTING FROM BSR 2018
Pain remains after rheumatoid arthritis diagnosis
AMSTERDAM – according to data from a large prospective study reported at the European Congress of Rheumatology.
At enrollment, 64% of patients still had remaining pain, and at 1 year, 24% had remaining pain, according to data from the Canadian Early Arthritis Cohort (CATCH).
Dr. Bykerk of the University of Toronto and the Hospital for Special Surgery, New York, presented the research on behalf of Yvonne C. Lee, MD, of Northwestern University, Chicago, and noted that they had previously published data showing the incidence of widespread pain was highest within the first year of an RA diagnosis and then plateaued (Ann Rheum Dis. 2013;72[6];949-54). This plateau could have been related to the control of inflammation, Dr. Bykerk observed.
“We think the first 12 months are really a critical window during which time acute inflammatory pain may transition, if you will, to chronic noninflammatory pain,” Dr. Bykerk said.
The aim of their current study was to look at the evolution of pain in the year following an RA diagnosis and to see whether there were any predictive factors for remaining pain and widespread pain. The latter might previously have been described as fibromyalgia, Dr. Bykerk said, and was defined as a difference between the tender and swollen 28-joint counts of at least seven points. Remaining pain was defined as a score of more than 4 on a pain intensity numerical rating scale.
Data on 1,270 patients who were enrolled in CATCH across 17 sites in Canada during 2007-2017 were used. The majority of the sample was female (73%) and white (82%) and had been experiencing symptoms for a median of 6 months. The mean age of patients was 54 years.
At enrollment, patients had a mean number of two comorbidities, with up to 12% having another condition that might contribute to pain, such as osteoarthritis (12%), a back or spinal problem (10%), or fibromyalgia (9%).
Most (72%) patients were being treated with methotrexate initially, either alone (29%) or in combination with other drugs, and almost two-thirds were using steroids, either orally (29%) or parenterally (32%). A small percentage (2%) were treated with biologics, but this is unusual until almost 12 months, Dr. Bykerk observed.
The baseline predictors for remaining pain at 1 year were high baseline pain (odds ratio, 2.1), sleep difficulties (OR, 2.2), and disability measured by the Health Assessment Questionnaire Disability Index (OR, 1.5). The latter was the strongest predictor for lingering widespread pain. The number of comorbidities were also predictive of lingering pain, though this was not a significant difference.
Assessing and considering treatment for these predictors may be important for improving persisting pain, Dr. Bykerk suggested. “In future we’d like to validate our findings with other validated questionnaires; we have a depression questionnaire now being used in the study, and we want to understand what subgroups of patients have different trajectories of pain.”
CATCH is currently funded via unrestricted research grants from Amgen, Pfizer, Bristol-Myers Squibb, Medexus, Eli Lilly, Merck, and Sandoz Canada Pharmaceuticals. Dr. Bykerk had no personal financial disclosures.
SOURCE: Lee YC et al. EULAR 2018 Congress.Abstract OP0349.
AMSTERDAM – according to data from a large prospective study reported at the European Congress of Rheumatology.
At enrollment, 64% of patients still had remaining pain, and at 1 year, 24% had remaining pain, according to data from the Canadian Early Arthritis Cohort (CATCH).
Dr. Bykerk of the University of Toronto and the Hospital for Special Surgery, New York, presented the research on behalf of Yvonne C. Lee, MD, of Northwestern University, Chicago, and noted that they had previously published data showing the incidence of widespread pain was highest within the first year of an RA diagnosis and then plateaued (Ann Rheum Dis. 2013;72[6];949-54). This plateau could have been related to the control of inflammation, Dr. Bykerk observed.
“We think the first 12 months are really a critical window during which time acute inflammatory pain may transition, if you will, to chronic noninflammatory pain,” Dr. Bykerk said.
The aim of their current study was to look at the evolution of pain in the year following an RA diagnosis and to see whether there were any predictive factors for remaining pain and widespread pain. The latter might previously have been described as fibromyalgia, Dr. Bykerk said, and was defined as a difference between the tender and swollen 28-joint counts of at least seven points. Remaining pain was defined as a score of more than 4 on a pain intensity numerical rating scale.
Data on 1,270 patients who were enrolled in CATCH across 17 sites in Canada during 2007-2017 were used. The majority of the sample was female (73%) and white (82%) and had been experiencing symptoms for a median of 6 months. The mean age of patients was 54 years.
At enrollment, patients had a mean number of two comorbidities, with up to 12% having another condition that might contribute to pain, such as osteoarthritis (12%), a back or spinal problem (10%), or fibromyalgia (9%).
Most (72%) patients were being treated with methotrexate initially, either alone (29%) or in combination with other drugs, and almost two-thirds were using steroids, either orally (29%) or parenterally (32%). A small percentage (2%) were treated with biologics, but this is unusual until almost 12 months, Dr. Bykerk observed.
The baseline predictors for remaining pain at 1 year were high baseline pain (odds ratio, 2.1), sleep difficulties (OR, 2.2), and disability measured by the Health Assessment Questionnaire Disability Index (OR, 1.5). The latter was the strongest predictor for lingering widespread pain. The number of comorbidities were also predictive of lingering pain, though this was not a significant difference.
Assessing and considering treatment for these predictors may be important for improving persisting pain, Dr. Bykerk suggested. “In future we’d like to validate our findings with other validated questionnaires; we have a depression questionnaire now being used in the study, and we want to understand what subgroups of patients have different trajectories of pain.”
CATCH is currently funded via unrestricted research grants from Amgen, Pfizer, Bristol-Myers Squibb, Medexus, Eli Lilly, Merck, and Sandoz Canada Pharmaceuticals. Dr. Bykerk had no personal financial disclosures.
SOURCE: Lee YC et al. EULAR 2018 Congress.Abstract OP0349.
AMSTERDAM – according to data from a large prospective study reported at the European Congress of Rheumatology.
At enrollment, 64% of patients still had remaining pain, and at 1 year, 24% had remaining pain, according to data from the Canadian Early Arthritis Cohort (CATCH).
Dr. Bykerk of the University of Toronto and the Hospital for Special Surgery, New York, presented the research on behalf of Yvonne C. Lee, MD, of Northwestern University, Chicago, and noted that they had previously published data showing the incidence of widespread pain was highest within the first year of an RA diagnosis and then plateaued (Ann Rheum Dis. 2013;72[6];949-54). This plateau could have been related to the control of inflammation, Dr. Bykerk observed.
“We think the first 12 months are really a critical window during which time acute inflammatory pain may transition, if you will, to chronic noninflammatory pain,” Dr. Bykerk said.
The aim of their current study was to look at the evolution of pain in the year following an RA diagnosis and to see whether there were any predictive factors for remaining pain and widespread pain. The latter might previously have been described as fibromyalgia, Dr. Bykerk said, and was defined as a difference between the tender and swollen 28-joint counts of at least seven points. Remaining pain was defined as a score of more than 4 on a pain intensity numerical rating scale.
Data on 1,270 patients who were enrolled in CATCH across 17 sites in Canada during 2007-2017 were used. The majority of the sample was female (73%) and white (82%) and had been experiencing symptoms for a median of 6 months. The mean age of patients was 54 years.
At enrollment, patients had a mean number of two comorbidities, with up to 12% having another condition that might contribute to pain, such as osteoarthritis (12%), a back or spinal problem (10%), or fibromyalgia (9%).
Most (72%) patients were being treated with methotrexate initially, either alone (29%) or in combination with other drugs, and almost two-thirds were using steroids, either orally (29%) or parenterally (32%). A small percentage (2%) were treated with biologics, but this is unusual until almost 12 months, Dr. Bykerk observed.
The baseline predictors for remaining pain at 1 year were high baseline pain (odds ratio, 2.1), sleep difficulties (OR, 2.2), and disability measured by the Health Assessment Questionnaire Disability Index (OR, 1.5). The latter was the strongest predictor for lingering widespread pain. The number of comorbidities were also predictive of lingering pain, though this was not a significant difference.
Assessing and considering treatment for these predictors may be important for improving persisting pain, Dr. Bykerk suggested. “In future we’d like to validate our findings with other validated questionnaires; we have a depression questionnaire now being used in the study, and we want to understand what subgroups of patients have different trajectories of pain.”
CATCH is currently funded via unrestricted research grants from Amgen, Pfizer, Bristol-Myers Squibb, Medexus, Eli Lilly, Merck, and Sandoz Canada Pharmaceuticals. Dr. Bykerk had no personal financial disclosures.
SOURCE: Lee YC et al. EULAR 2018 Congress.Abstract OP0349.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: A substantial number of patients have pain 1 year after being diagnosed with rheumatoid arthritis.
Major finding: Remaining pain and widespread pain were a respective 64% and 9% at baseline and 9% and 5% at 1 year.
Study details: A prospective, observational, cohort of 1,270 patients with new-onset inflammatory arthritis.
Disclosures: Dr. Bykerk is the principle investigator of the Canadian Early Arthritis Cohort (CATCH). CATCH is currently funded via unrestricted research grants from Amgen, Pfizer, Bristol-Myers Squibb, Medexus, Eli Lilly, Merck, and Sandoz Canada Pharmaceuticals. Dr. Bykerk had no personal financial disclosures.
Source: Lee YC et al. EULAR 2018 Congress, Abstract OP0349.
High RA biologic drug levels linked with more infections
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.
The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.
The study used data and specimens collected in two separate, prospective U.K. studies: the British Society for Rheumatology Biologics Register-RA, which had data from more than 20,000 U.K. patients with RA who started treatment with a biologic agent, and BRAGGSS (Biologics in Rheumatoid Arthritis and Genetics and Genomics Study Syndicate), a national prospective cohort of 3,000 RA patients who had serum specimens drawn at 3, 6, and 12 months after starting biologic drug treatment and tested by an immunoassay for the concentration of the drug each patient received.
Dr. Jani and her associates considered serum levels that exceeded the following thresholds to categorize patients as having a high drug level: 8 mcg/mL adalimumab, 25 mcg/mL certolizumab, 4 mcg/mL etanercept, 4 mcg/mL infliximab, and 4 mcg/mL tocilizumab. The patients averaged about 59 years old, about three-quarters were women, and they had been diagnosed with RA for approximately 5-7 years. About 22% were also on treatment with a steroid, and most patients had not received prior treatment with a biologic agent.
The researchers tallied 229 diagnosed infections in the subgroup with high serum levels of their biologic drug, and 63 infections in those with levels below this threshold. After adjustment for age, sex, methotrexate use, and disease activity score, patients with high serum levels of their biologic drug had a 51% higher rate of all infections than did patients with levels that fell below the high-level threshold, reported Dr. Jani, a rheumatologist at Manchester (England) University. Analysis of the accumulation of infections over the course of 1 year of follow-up showed that this difference in infection rates became apparent after about 2 months of exposure and then began to diverge more sharply after about 5 months of exposure.
The results also showed that the rate of serious infections – defined as those needing intravenous antibiotics, hospitalization, or resulting in death – were similar in the two subgroups. The types of infections and their relative frequencies were also roughly similar in the two subgroups. Lower respiratory infections were the most common infection in both subgroups, followed by infections of the upper respiratory tract, urinary tract, and skin as the next three most common infections in both subgroups.
SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point:
Major finding: High serum levels of a biologic drug were linked with a 51% higher infection rate, compared with those who had normal or low levels.
Study details: Prospective data collected from 703 patients throughout the United Kingdom.
Disclosures: Dr. Jani had no relevant disclosures. Dr. Isaacs has been a consultant to several companies that market biologic drugs for treating rheumatoid arthritis.
Source: Jani M et al. EULAR 2018 Congress, Abstract OP0229.
EULAR recommendations on steroids: ‘As necessary, but as little as possible’
AMSTERDAM – Glucocorticosteroids remain an important therapeutic option for many patients with rheumatic and nonrheumatic disease, but careful assessment of their relative benefits and risks needs to be considered when prescribing, according to an expert summary of currently available European League Against Rheumatism (EULAR) recommendations.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
From rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) to vasculitis, myositis, and even gout, steroids are widely used in the rheumatic diseases, said Frank Buttgereit, MD, during a final plenary session at the European Congress of Rheumatology.
“These are strong-acting, rapidly acting, efficacious drugs,” observed Dr. Buttgereit, who is a professor in the department of rheumatology at Charité–Universitätsmedizin Berlin. While effective at reducing inflammation and providing immunosuppression, they are, of course, not without their well-known risks. Some of the well-documented risks he pointed out were the development of osteoporosis, myopathy, and edema; the disruption of lipid and carbohydrate metabolism; and the risk of developing glaucoma and cataracts.
“This leads to the question on how to optimize the use of these drugs,” Dr. Buttgereit said. “EULAR is constantly working to improve its guidelines,” and updating these in line with the available evidence, he added. “The bottom line is always give as much as necessary but as little as possible.”
Over the past few years, EULAR’s Glucocorticoid Task Force has been reviewing and updating recommendations on the use of these drugs and it has published several important documents clarifying their use in RA and in PMR. The task force has also published a viewpoint article on the long-term use of steroids, defining the conditions where an “acceptably low level of harm” might exist to enable their continued use. There have also been separate recommendations, published in 2010, on how to monitor these drugs (Ann Rheum Dis. 2010;69[11]:1913-9).
Clarifying the role of steroids in rheumatoid arthritis
The latest (2016) EULAR recommendations on the use of glucocorticosteroids were published last year (Ann Rheum Dis. 2017;76[6]:960-77) and included an important adjustment on when they should be initially used in RA, Dr. Buttgereit explained. Previous recommendations had said that steroids could be combined with disease-modifying antirheumatic drugs (DMARDs) but had suggested that they be used at a low dose. Now the wording has changed to focus on short-term use rather than dosing.
“Glucocorticoids can be given initially at different dosages, and using different routes of administration,” he said in a video interview at the EULAR Congress. The practice on what dose to give varies from country to country, he noted, so the recommendations are now being less prescriptive.
“We have made it clear that glucocorticoids should really be used only when initiating conventional synthetic DMARDs, but not necessarily if you switch to biologics or targeted synthetics because usually the onset of their actions is pretty fast,” Dr. Buttgereit said.
One thing that hasn’t changed is that steroid should be tapered down as “rapidly as clinically feasible” until, ideally, their full withdrawal. Although there are cases when that might not be possible, and their long-term use might be warranted. This is when you get into discussion about the benefit-to-risk ratio, he said.
Steroids for polymyalgia rheumatica
Steroids may be used as monotherapy in patients with PMR, Dr. Buttgereit observed, which is in contrast to other conditions such as RA. Although the evidence for use of steroids in PMR is limited, the EULAR Glucocorticoid Task Force and American College of Rheumatology recommended (Ann Rheum Dis. 2015;74[10]:1799-807) using a starting dose of a prednisolone-equivalent dose between 12.5 and 25 mg/day, and if there is an improvement in few weeks, the dose can start to be reduced. Tapering should be rapid at first to bring the dose down to 10 mg/day and followed by a more gradual dose-reduction phase.
“So, you can see we are giving more or less precise recommendations on how to start, how to taper,” Dr. Buttgereit said.
Balancing long-term benefit vs. harm
Balancing the long-term benefits and risks of steroids in rheumatic disease was the focus of a EULAR viewpoint article published 3 years ago in 2015 (Ann Rheum Dis. 2015;75[6]:952-7).
Three main messages can be drawn out of this work, Dr. Buttgereit said.
First, treatment with steroids for 3-6 months is associated with more benefits than risks if doses of 5 mg/day or less are used. There is one important exception to this, however, and that is the use of steroids in patients with comorbid cardiovascular disease.
Second, using doses of 10 mg/day for long periods tips the balance toward more risks than benefits, and “this means you should avoid this.”
Third, doses of 5-10 mg/day may be appropriate, but there are certain patient factors that will influence the benefit-to-harm ratio that need to be considered. These include older age, smoking, high alcohol consumption, and poor nutrition. There are also factors that may help protect the patients from risk, such as early diagnosis, low disease activity, low cumulative dose of steroids, and a shorter duration of treatment.
“It’s not only the dose, it’s also the absence or presence of risk factors and/or preventive measures,” that’s important, Dr. Buttgereit said.
Dr. Buttgereit has received consultancy fees, honoraria, and/or travel expenses from Amgen, Horizon Pharma, Mundipharma, Roche, and Pfizer and grant or study support from Amgen, Mundipharma, and Pfizer.
SOURCE: Buttgereit F. EULAR 2018 Congress, Abstract SP160.
AMSTERDAM – Glucocorticosteroids remain an important therapeutic option for many patients with rheumatic and nonrheumatic disease, but careful assessment of their relative benefits and risks needs to be considered when prescribing, according to an expert summary of currently available European League Against Rheumatism (EULAR) recommendations.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
From rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) to vasculitis, myositis, and even gout, steroids are widely used in the rheumatic diseases, said Frank Buttgereit, MD, during a final plenary session at the European Congress of Rheumatology.
“These are strong-acting, rapidly acting, efficacious drugs,” observed Dr. Buttgereit, who is a professor in the department of rheumatology at Charité–Universitätsmedizin Berlin. While effective at reducing inflammation and providing immunosuppression, they are, of course, not without their well-known risks. Some of the well-documented risks he pointed out were the development of osteoporosis, myopathy, and edema; the disruption of lipid and carbohydrate metabolism; and the risk of developing glaucoma and cataracts.
“This leads to the question on how to optimize the use of these drugs,” Dr. Buttgereit said. “EULAR is constantly working to improve its guidelines,” and updating these in line with the available evidence, he added. “The bottom line is always give as much as necessary but as little as possible.”
Over the past few years, EULAR’s Glucocorticoid Task Force has been reviewing and updating recommendations on the use of these drugs and it has published several important documents clarifying their use in RA and in PMR. The task force has also published a viewpoint article on the long-term use of steroids, defining the conditions where an “acceptably low level of harm” might exist to enable their continued use. There have also been separate recommendations, published in 2010, on how to monitor these drugs (Ann Rheum Dis. 2010;69[11]:1913-9).
Clarifying the role of steroids in rheumatoid arthritis
The latest (2016) EULAR recommendations on the use of glucocorticosteroids were published last year (Ann Rheum Dis. 2017;76[6]:960-77) and included an important adjustment on when they should be initially used in RA, Dr. Buttgereit explained. Previous recommendations had said that steroids could be combined with disease-modifying antirheumatic drugs (DMARDs) but had suggested that they be used at a low dose. Now the wording has changed to focus on short-term use rather than dosing.
“Glucocorticoids can be given initially at different dosages, and using different routes of administration,” he said in a video interview at the EULAR Congress. The practice on what dose to give varies from country to country, he noted, so the recommendations are now being less prescriptive.
“We have made it clear that glucocorticoids should really be used only when initiating conventional synthetic DMARDs, but not necessarily if you switch to biologics or targeted synthetics because usually the onset of their actions is pretty fast,” Dr. Buttgereit said.
One thing that hasn’t changed is that steroid should be tapered down as “rapidly as clinically feasible” until, ideally, their full withdrawal. Although there are cases when that might not be possible, and their long-term use might be warranted. This is when you get into discussion about the benefit-to-risk ratio, he said.
Steroids for polymyalgia rheumatica
Steroids may be used as monotherapy in patients with PMR, Dr. Buttgereit observed, which is in contrast to other conditions such as RA. Although the evidence for use of steroids in PMR is limited, the EULAR Glucocorticoid Task Force and American College of Rheumatology recommended (Ann Rheum Dis. 2015;74[10]:1799-807) using a starting dose of a prednisolone-equivalent dose between 12.5 and 25 mg/day, and if there is an improvement in few weeks, the dose can start to be reduced. Tapering should be rapid at first to bring the dose down to 10 mg/day and followed by a more gradual dose-reduction phase.
“So, you can see we are giving more or less precise recommendations on how to start, how to taper,” Dr. Buttgereit said.
Balancing long-term benefit vs. harm
Balancing the long-term benefits and risks of steroids in rheumatic disease was the focus of a EULAR viewpoint article published 3 years ago in 2015 (Ann Rheum Dis. 2015;75[6]:952-7).
Three main messages can be drawn out of this work, Dr. Buttgereit said.
First, treatment with steroids for 3-6 months is associated with more benefits than risks if doses of 5 mg/day or less are used. There is one important exception to this, however, and that is the use of steroids in patients with comorbid cardiovascular disease.
Second, using doses of 10 mg/day for long periods tips the balance toward more risks than benefits, and “this means you should avoid this.”
Third, doses of 5-10 mg/day may be appropriate, but there are certain patient factors that will influence the benefit-to-harm ratio that need to be considered. These include older age, smoking, high alcohol consumption, and poor nutrition. There are also factors that may help protect the patients from risk, such as early diagnosis, low disease activity, low cumulative dose of steroids, and a shorter duration of treatment.
“It’s not only the dose, it’s also the absence or presence of risk factors and/or preventive measures,” that’s important, Dr. Buttgereit said.
Dr. Buttgereit has received consultancy fees, honoraria, and/or travel expenses from Amgen, Horizon Pharma, Mundipharma, Roche, and Pfizer and grant or study support from Amgen, Mundipharma, and Pfizer.
SOURCE: Buttgereit F. EULAR 2018 Congress, Abstract SP160.
AMSTERDAM – Glucocorticosteroids remain an important therapeutic option for many patients with rheumatic and nonrheumatic disease, but careful assessment of their relative benefits and risks needs to be considered when prescribing, according to an expert summary of currently available European League Against Rheumatism (EULAR) recommendations.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
From rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) to vasculitis, myositis, and even gout, steroids are widely used in the rheumatic diseases, said Frank Buttgereit, MD, during a final plenary session at the European Congress of Rheumatology.
“These are strong-acting, rapidly acting, efficacious drugs,” observed Dr. Buttgereit, who is a professor in the department of rheumatology at Charité–Universitätsmedizin Berlin. While effective at reducing inflammation and providing immunosuppression, they are, of course, not without their well-known risks. Some of the well-documented risks he pointed out were the development of osteoporosis, myopathy, and edema; the disruption of lipid and carbohydrate metabolism; and the risk of developing glaucoma and cataracts.
“This leads to the question on how to optimize the use of these drugs,” Dr. Buttgereit said. “EULAR is constantly working to improve its guidelines,” and updating these in line with the available evidence, he added. “The bottom line is always give as much as necessary but as little as possible.”
Over the past few years, EULAR’s Glucocorticoid Task Force has been reviewing and updating recommendations on the use of these drugs and it has published several important documents clarifying their use in RA and in PMR. The task force has also published a viewpoint article on the long-term use of steroids, defining the conditions where an “acceptably low level of harm” might exist to enable their continued use. There have also been separate recommendations, published in 2010, on how to monitor these drugs (Ann Rheum Dis. 2010;69[11]:1913-9).
Clarifying the role of steroids in rheumatoid arthritis
The latest (2016) EULAR recommendations on the use of glucocorticosteroids were published last year (Ann Rheum Dis. 2017;76[6]:960-77) and included an important adjustment on when they should be initially used in RA, Dr. Buttgereit explained. Previous recommendations had said that steroids could be combined with disease-modifying antirheumatic drugs (DMARDs) but had suggested that they be used at a low dose. Now the wording has changed to focus on short-term use rather than dosing.
“Glucocorticoids can be given initially at different dosages, and using different routes of administration,” he said in a video interview at the EULAR Congress. The practice on what dose to give varies from country to country, he noted, so the recommendations are now being less prescriptive.
“We have made it clear that glucocorticoids should really be used only when initiating conventional synthetic DMARDs, but not necessarily if you switch to biologics or targeted synthetics because usually the onset of their actions is pretty fast,” Dr. Buttgereit said.
One thing that hasn’t changed is that steroid should be tapered down as “rapidly as clinically feasible” until, ideally, their full withdrawal. Although there are cases when that might not be possible, and their long-term use might be warranted. This is when you get into discussion about the benefit-to-risk ratio, he said.
Steroids for polymyalgia rheumatica
Steroids may be used as monotherapy in patients with PMR, Dr. Buttgereit observed, which is in contrast to other conditions such as RA. Although the evidence for use of steroids in PMR is limited, the EULAR Glucocorticoid Task Force and American College of Rheumatology recommended (Ann Rheum Dis. 2015;74[10]:1799-807) using a starting dose of a prednisolone-equivalent dose between 12.5 and 25 mg/day, and if there is an improvement in few weeks, the dose can start to be reduced. Tapering should be rapid at first to bring the dose down to 10 mg/day and followed by a more gradual dose-reduction phase.
“So, you can see we are giving more or less precise recommendations on how to start, how to taper,” Dr. Buttgereit said.
Balancing long-term benefit vs. harm
Balancing the long-term benefits and risks of steroids in rheumatic disease was the focus of a EULAR viewpoint article published 3 years ago in 2015 (Ann Rheum Dis. 2015;75[6]:952-7).
Three main messages can be drawn out of this work, Dr. Buttgereit said.
First, treatment with steroids for 3-6 months is associated with more benefits than risks if doses of 5 mg/day or less are used. There is one important exception to this, however, and that is the use of steroids in patients with comorbid cardiovascular disease.
Second, using doses of 10 mg/day for long periods tips the balance toward more risks than benefits, and “this means you should avoid this.”
Third, doses of 5-10 mg/day may be appropriate, but there are certain patient factors that will influence the benefit-to-harm ratio that need to be considered. These include older age, smoking, high alcohol consumption, and poor nutrition. There are also factors that may help protect the patients from risk, such as early diagnosis, low disease activity, low cumulative dose of steroids, and a shorter duration of treatment.
“It’s not only the dose, it’s also the absence or presence of risk factors and/or preventive measures,” that’s important, Dr. Buttgereit said.
Dr. Buttgereit has received consultancy fees, honoraria, and/or travel expenses from Amgen, Horizon Pharma, Mundipharma, Roche, and Pfizer and grant or study support from Amgen, Mundipharma, and Pfizer.
SOURCE: Buttgereit F. EULAR 2018 Congress, Abstract SP160.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: When dosing glucocorticoids, give as much as necessary but as little as possible.
Major finding:
Disclosures: Dr. Buttgereit has received consultancy fees, honoraria, and/or travel expenses from Amgen, Horizon Pharma, Mundipharma, Roche, and Pfizer and grant or study support from Amgen, Mundipharma, and Pfizer.
Source: Buttgereit F. EULAR 2018 Congress. Abstract SP160.
Glucocorticosteroid use raises sarcopenia risk in RA
AMSTERDAM – Patients with RA have a higher risk of developing sarcopenia if they are treated with glucocorticosteroids, study findings suggested.
“The strength of our study is that it is a prospective, longitudinal study and this study is the first, to our knowledge, to look at risk factors for sarcopenia limited to RA patients,” Yutaro Yamada, MD, said in an interview at the European Congress of Rheumatology.
Dr. Yamada, of the department of orthopedic surgery at Osaka City University, Japan, said that there is a twofold rationale for looking at risk factors for sarcopenia in RA patients. First, RA causes chronic inflammation and this in turn is thought to lead to a metabolic state that then results in muscle loss. Furthermore, joint dysfunction and subsequent disuse likely contribute to weakening muscles. Second, glucocorticosteroids, which are commonly used to treat patients with RA, have themselves been associated with a low muscle area in prior research.
In 2016, the CHIKARA study was initiated “to clarify the correlation between RA disease activity and sarcopenia,” Dr. Yamada and his associates reported in a poster presentation. They recruited 100 patients, of whom 78% were women, and recorded body weight, muscle mass, fat mass, and predicted bone mass using a body composition analyzer at entry and 1 year later. Laboratory data and disease activity parameters were also assessed, along with radiologic findings and ability to perform activities of daily living. Patients’ treatment was also recorded.
At baseline, the mean age of study participants was 68 years with a mean disease duration of 5.5 years. The majority (86%) had been treated with methotrexate, with 26% also using glucocorticosteroids, and 30% using biologic agents.
Just over one-quarter (28%) were diagnosed with sarcopenia over the course of 1 year. Sarcopenia was defined by criteria agreed by the Asia Working Group on Sarcopenia (Am Med Dir Assoc. 2014;15[2]:95-101) that set thresholds for low muscle mass, low muscle strength, and low physical performance.
Comparing the 9 patients who did develop sarcopenia with the 86 who did not, the researchers found that sarcopenia patients tended to be younger (66.7 vs. 80.2 years), although the difference was not statistically significant. Interestingly, however, more than half (55.6%) of patients who developed sarcopenia were using glucocorticosteroids, compared with 22% of those who were not (P = .029). Of note, the average glucocorticosteroid dose was just 2 mg/day. Patients who developed sarcopenia were also observed to have a lower fat mass (11.7 vs. 15.8, P = .058).
A multiple logistic regression analysis found that using a glucocorticosteroid dose of 2 mg/day or more and lower body fat mass (odds ratio, 0.78; 95% CI 0.61-0.98; P = 0.037) were significant variables for the onset of sarcopenia.
Dr. Yamada noted that 2 mg/day is “a relatively low dose” and so avoiding glucocorticosteroid therapy in those at risk of sarcopenia, particularly those with a low fat mass, may be something to consider.
The study did not receive commercial funding, and Dr. Yamada had no conflicts of interest to disclose.
SOURCE: Yamada Y et al. Ann Rheum Dis. 2018;77(Suppl 2):308-9. Abstract THU0181.
AMSTERDAM – Patients with RA have a higher risk of developing sarcopenia if they are treated with glucocorticosteroids, study findings suggested.
“The strength of our study is that it is a prospective, longitudinal study and this study is the first, to our knowledge, to look at risk factors for sarcopenia limited to RA patients,” Yutaro Yamada, MD, said in an interview at the European Congress of Rheumatology.
Dr. Yamada, of the department of orthopedic surgery at Osaka City University, Japan, said that there is a twofold rationale for looking at risk factors for sarcopenia in RA patients. First, RA causes chronic inflammation and this in turn is thought to lead to a metabolic state that then results in muscle loss. Furthermore, joint dysfunction and subsequent disuse likely contribute to weakening muscles. Second, glucocorticosteroids, which are commonly used to treat patients with RA, have themselves been associated with a low muscle area in prior research.
In 2016, the CHIKARA study was initiated “to clarify the correlation between RA disease activity and sarcopenia,” Dr. Yamada and his associates reported in a poster presentation. They recruited 100 patients, of whom 78% were women, and recorded body weight, muscle mass, fat mass, and predicted bone mass using a body composition analyzer at entry and 1 year later. Laboratory data and disease activity parameters were also assessed, along with radiologic findings and ability to perform activities of daily living. Patients’ treatment was also recorded.
At baseline, the mean age of study participants was 68 years with a mean disease duration of 5.5 years. The majority (86%) had been treated with methotrexate, with 26% also using glucocorticosteroids, and 30% using biologic agents.
Just over one-quarter (28%) were diagnosed with sarcopenia over the course of 1 year. Sarcopenia was defined by criteria agreed by the Asia Working Group on Sarcopenia (Am Med Dir Assoc. 2014;15[2]:95-101) that set thresholds for low muscle mass, low muscle strength, and low physical performance.
Comparing the 9 patients who did develop sarcopenia with the 86 who did not, the researchers found that sarcopenia patients tended to be younger (66.7 vs. 80.2 years), although the difference was not statistically significant. Interestingly, however, more than half (55.6%) of patients who developed sarcopenia were using glucocorticosteroids, compared with 22% of those who were not (P = .029). Of note, the average glucocorticosteroid dose was just 2 mg/day. Patients who developed sarcopenia were also observed to have a lower fat mass (11.7 vs. 15.8, P = .058).
A multiple logistic regression analysis found that using a glucocorticosteroid dose of 2 mg/day or more and lower body fat mass (odds ratio, 0.78; 95% CI 0.61-0.98; P = 0.037) were significant variables for the onset of sarcopenia.
Dr. Yamada noted that 2 mg/day is “a relatively low dose” and so avoiding glucocorticosteroid therapy in those at risk of sarcopenia, particularly those with a low fat mass, may be something to consider.
The study did not receive commercial funding, and Dr. Yamada had no conflicts of interest to disclose.
SOURCE: Yamada Y et al. Ann Rheum Dis. 2018;77(Suppl 2):308-9. Abstract THU0181.
AMSTERDAM – Patients with RA have a higher risk of developing sarcopenia if they are treated with glucocorticosteroids, study findings suggested.
“The strength of our study is that it is a prospective, longitudinal study and this study is the first, to our knowledge, to look at risk factors for sarcopenia limited to RA patients,” Yutaro Yamada, MD, said in an interview at the European Congress of Rheumatology.
Dr. Yamada, of the department of orthopedic surgery at Osaka City University, Japan, said that there is a twofold rationale for looking at risk factors for sarcopenia in RA patients. First, RA causes chronic inflammation and this in turn is thought to lead to a metabolic state that then results in muscle loss. Furthermore, joint dysfunction and subsequent disuse likely contribute to weakening muscles. Second, glucocorticosteroids, which are commonly used to treat patients with RA, have themselves been associated with a low muscle area in prior research.
In 2016, the CHIKARA study was initiated “to clarify the correlation between RA disease activity and sarcopenia,” Dr. Yamada and his associates reported in a poster presentation. They recruited 100 patients, of whom 78% were women, and recorded body weight, muscle mass, fat mass, and predicted bone mass using a body composition analyzer at entry and 1 year later. Laboratory data and disease activity parameters were also assessed, along with radiologic findings and ability to perform activities of daily living. Patients’ treatment was also recorded.
At baseline, the mean age of study participants was 68 years with a mean disease duration of 5.5 years. The majority (86%) had been treated with methotrexate, with 26% also using glucocorticosteroids, and 30% using biologic agents.
Just over one-quarter (28%) were diagnosed with sarcopenia over the course of 1 year. Sarcopenia was defined by criteria agreed by the Asia Working Group on Sarcopenia (Am Med Dir Assoc. 2014;15[2]:95-101) that set thresholds for low muscle mass, low muscle strength, and low physical performance.
Comparing the 9 patients who did develop sarcopenia with the 86 who did not, the researchers found that sarcopenia patients tended to be younger (66.7 vs. 80.2 years), although the difference was not statistically significant. Interestingly, however, more than half (55.6%) of patients who developed sarcopenia were using glucocorticosteroids, compared with 22% of those who were not (P = .029). Of note, the average glucocorticosteroid dose was just 2 mg/day. Patients who developed sarcopenia were also observed to have a lower fat mass (11.7 vs. 15.8, P = .058).
A multiple logistic regression analysis found that using a glucocorticosteroid dose of 2 mg/day or more and lower body fat mass (odds ratio, 0.78; 95% CI 0.61-0.98; P = 0.037) were significant variables for the onset of sarcopenia.
Dr. Yamada noted that 2 mg/day is “a relatively low dose” and so avoiding glucocorticosteroid therapy in those at risk of sarcopenia, particularly those with a low fat mass, may be something to consider.
The study did not receive commercial funding, and Dr. Yamada had no conflicts of interest to disclose.
SOURCE: Yamada Y et al. Ann Rheum Dis. 2018;77(Suppl 2):308-9. Abstract THU0181.
REPORTING FROM THE EULAR 2018 CONGRESS
Key clinical point: Patients with RA and a lean body mass have a heightened risk of developing sarcopenia if they are treated with glucocorticosteroids.
Major finding: Using glucocorticosteroids at doses of 2 mg/day or more significantly increased the odds of developing sarcopenia (odds ratio, 8.0; 95% confidence interval, 1.17-54.8; P = .034).
Study details: The CHIKARA study – a prospective, observational study involving 100 patients with RA.
Disclosures: The study did not receive commercial funding, and Dr. Yamada had no conflicts of interest to disclose.
Source: Yamada Y et al. Ann Rheum Dis. 2018;77(Suppl 2):308-9. Abstract THU0181.