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FDA advisory committee votes to recommend update to celecoxib safety labeling
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
SILVER SPRING, MD. – An FDA advisory committee voted (15 yes, 5 no, 1 abstention) to update the safety information in the label of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), for use in patients with osteoarthritis (OA) and rheumatoid arthritis, on the basis of results of the PRECISION trial.
A Joint Meeting ofthe Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee was convened April 24-25 to address two issues, the first being the consideration of Pfizer’s application for celecoxib and the second, to assess the safety of celecoxib and other common NSAIDs like ibuprofen and naproxen.
The randomized controlled PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen) trial compared celecoxib, naproxen, and ibuprofen and their cardiovascular outcomes. The PRECISION trial was undertaken after another selective COX-2 inhibitor, rofecoxib (Vioxx), was withdrawn from the market because of associated cardiovascular events. It compared the three drugs among more than 24,000 patients with painful arthritis and elevated cardiovascular risk.
Main results showed that the rates of cardiovascular events (cardiovascular death, myocardial infarction, or stroke) were 2.3% with celecoxib, 2.5% with naproxen, and 2.7% with ibuprofen during a follow-up approaching 3 years, showing noninferiority for celecoxib.
In a post hoc analysis presented by Steven Nissen, MD, patients taking ibuprofen and naproxen experienced adjudicated cardiovascular, GI, or renal events 28% and 15% more than did patients taking celecoxib.
The results of the study could inform clinical strategy, said Dr. Nissen, chair of cardiovascular medicine at the Cleveland Clinic in Ohio. “For arthritis patients who require NSAIDs to achieve an acceptable quality of life, particularly those at high cardiovascular, GI, or renal risk, the PRECISION trial suggests that a clinical strategy of starting patients on celecoxib 200 mg daily may be the safest approach, reserving full therapeutic doses of ibuprofen and naproxen for patients who do not respond to celecoxib."
REPORTING FROM AN FDA ADVISORY COMMITTEE MEETING
FDA advisory committee recommends baricitinib 2 mg to treat rheumatoid arthritis
The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.
In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.
The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.
The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.
Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.
“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”
Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.
“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.
Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.
The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.
RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.
RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.
RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).
RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.
RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).
Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.
The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.
In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.
The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.
The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.
Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.
“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”
Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.
“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.
Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.
The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.
RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.
RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.
RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).
RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.
RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).
Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.
The Food and Drug Administration Arthritis Advisory Committee has voted to recommend the 2-mg dose of baricitinib, an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis who have responded inadequately or poorly to methotrexate but rejected a 4-mg dose of the same drug.
In separate votes on efficacy of the 2-mg and 4-mg doses of baricitinib (14-1 and 15-0, respectively), on their safety (9-6 and 4-11), and on their benefit-risk ratio (10-5 and 5-10), the advisory committee consistently backed the 2-mg dose, but the committee rejected the 4-mg dose despite its effectiveness in improving the symptoms of rheumatoid arthritis. Although the FDA does not always follow the advice of its advisory committees, it generally does.
The New Drug Application was resubmitted by Eli Lilly and Incyte. The proposed doses included a 2-mg once-daily dose and a 4-mg dose for some patients. The original submission was filed in January of 2016 with an indication to treat moderate to severe rheumatoid arthritis, but that application was rejected primarily because of concerns about thrombotic events. Other issues with the original application included inadequate safety exposure for the 2-mg dose of baricitinib, as well as inconsistent findings concerning the efficacy of the higher 4-mg dose.
The resubmission addressed several of the issues noted by the FDA, and changed the indication to treat patients with moderate to severe RA who have had an inadequate response to methotrexate. Along with the different indication, the dosing regimen shifted to 2 mg once daily. For patients who did not adequately respond to disease-modifying antirheumatic drugs (DMARDS) or had an intolerance for one or more of these drugs, a 4-mg dose was recommended; after disease activity had been controlled, a taper to 2 mg once daily could be considered.
Apart from changes in the drug dosage and indication, the resubmission also included accumulated safety data, comparative epidemiologic data concerning venous thromboembolism and pulmonary embolism, and efficacy analyses to support the new dosing recommendations.
“The risk-benefit ratio may be less good here,” stated Donald Miller, PharmD, a professor of pharmacy practice at North Dakota State University, Fargo. “If there is a safety issue, it’s more likely to be a problem with the 4-mg dose.”
Jon Russell, MD, PhD, medical director of Fibromyalgia Research and Consulting, San Antonio, felt that the manufacturer understood that the safety signal indicated that the benefits outweighed the risks with the 4-mg dose of baricitinib.
“The drug is efficacious in resistant rheumatoid arthritis, and rheumatoid arthritis is a devastating disease. Organs are being destroyed, joints as well as organs, and it’s war. We need to make the patient aware that it’s war and then fight it like it is,” he said.
Many of the committee members mentioned that the efficacies of the 2-mg and 4-mg doses were not in question, primarily based on the data from four phase 3 clinical trials.
The studies RA-BEACON (JADW), RA-BUILD (JADX), RA-BEGIN (JADZ), and RA-BEAM (JADV) were all randomized phase 3 trials that evaluated the efficacy of baricitinib in patients with moderate to severe RA.
RA-BEACON and RA-BUILD both had similar designs and compared 2-mg and 4-mg doses of baricitinib with placebo; the trials primarily differed in their patient populations.
RA-BEACON. Investigators looked at 527 randomized patients who had failed treatment with a biologic DMARD with nearly half failing multiple classes of this drug. The primary endpoint for this study was met, with the 4-mg dose showing superior results, compared with placebo, based on American College of Rheumatology (ACR) 20 scores (P less than .0001). As early as week 1 of the trial, both patients receiving 2 mg and those receiving 4 mg of baricitinib showed significant improvement, compared with placebo. By week 4, the 4-mg dose produced as much improvement as the 2-mg dose achieved over nearly 6 months. While the 4-mg dose was considered more effective, the 2-mg dose showed improvement in ACR 20 scores, change in Disease Activity Score 28 C-reactive protein (DAS28-CRP), and change in health assessment questionnaire disability index (HAQ-DI) (P less than .001). Neither the 4-mg nor the 2-mg dose was able to reduce Simple Disease Activity Index (SDAI) scores, a difficult endpoint to achieve, particularly in such a short time frame.
RA-BUILD. The researchers looked at patients who had failed treatment with conventional DMARDs and had not been treated with biologic DMARDS. The investigators looked at 684 randomized patients and saw similar results to RA-BEACON, with both the 2-mg and 4-mg doses displaying significant improvement in ACR 20, change in DAS28-CRP, and change in HAQ-DI, as well as SDAI remission which had been absent in RA-BEACON. Patients taking the 4-mg dose showed improvement in morning joint stiffness duration and severity (P less than .0001), as well as improvements in worst joint pain (P less than .0001) and tiredness (P less than .027).
RA-BEGIN. The investigators took a different approach and compared various drug combinations, including baricitinib 4 mg alone or in combination with oral methotrexate or in patients taking methotrexate who were DMARD-naive. Ultimately, this trial displayed that baricitinib 4 mg alone was superior to methotrexate, according to ACR 20 scores. This held true across all clinical measures at week 24 whether baricitinib was administered alone or in combination with methotrexate. As it had in the previously discussed trials, the 4-mg dose improved all of the previously mentioned test scores, compared with methotrexate (P less than .0001) except for modified Total Sharp Score (mTSS) (P = 0.158). When baricitinib 4 mg was used in conjunction with methotrexate, improvements in test scores, including mTSS, were statistically significant.
RA-BEAM. The researchers compared baricitinib 4 mg with placebo and adalimumab in 1,305 patients. All patients maintained a background level of methotrexate to improve the efficacy of adalimumab. Consistent with previous studies, baricitinib 4 mg outperformed other therapies and placebo in improvement in ACR 20, change in DAS28-CRP, change in HAQ-DI, and SDAI remission, as well as improvements in morning joint stiffness duration and severity, worst joint pain, and worst tiredness (P less than .0001).
Despite the clear efficacy of baricitinib 4 mg, the primary issue of contention was safety and benefit-to-risk ratio. The primary safety concerns were serious infection from opportunistic pathogens, herpes zoster, various malignancies, arterial and venous thrombosis, and laboratory abnormalities including elevated platelet counts and liver test elevations.
MACE risk similar across arthritis subtypes
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis were linked to similarly increased risks of major adverse cardiovascular events in a large population-based cohort study.
Inflammation itself drives this relationship and “adequate control of disease activity is needed to lower cardiovascular risk,” wrote Kim Lauper, MD, of Geneva University Hospitals, and her coinvestigators.
Major adverse cardiovascular events (MACE) also were significantly associated with traditional cardiovascular risk factors such as smoking, hypertension, and hyperlipidemia, “stressing the importance of [their] detection and management,” the researchers wrote in Arthritis Care and Research.
Previous studies linked inflammatory arthritis to a 40%-50% increase in risk of cardiovascular events, such as MI and acute coronary syndrome. Inflammatory arthritis also increases the risk of cerebrovascular disease, and traditional cardiovascular risk factors alone do not explain these associations, the researchers noted. Mounting data suggest that inflammation underlies the pathogenesis of atherosclerosis. Other studies have documented the cardioprotective effect of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis and psoriasis.
Dr. Lauper and her coinvestigators examined the prevalence and incidence of MACE, including MI, transient or permanent cerebrovascular events, or cardiovascular deaths among patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. The 5,315 patients in the study were part of the Swiss Clinical Quality Management registry, which longitudinally tracks individuals throughout Switzerland who receive biologic DMARDs.
The investigators also asked rheumatologists to supply missing data and used a questionnaire to survey patients about cardiovascular events and associated risk factors. These efforts produced more than 66,000 patient-years of follow-up data, more than half of which were for rheumatoid arthritis and less than 10,000 of which were for psoriatic arthritis.
For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. Patients with rheumatoid arthritis tended to be older, which explained most of their excess risk of MACE, the researchers said. Controlling for age only, MACE incidence rate ratios were 1.16 for spondyloarthritis (P = .52) and 0.75 for psoriatic arthritis (P = .34).
The analysis of prevalent MACE included more than 5,000 patients. Nonfatal MACE had affected 4.8% of patients with rheumatoid arthritis, 2.2% of patients with axial spondyloarthritis, and 2.9% of patients with psoriatic arthritis (P less than .001). Once again, differences among groups were not significant after researchers controlled for the older age of the rheumatoid arthritis patients.
Among all patients, independent risk factors for MACE included older age (P less than .001), disease duration (P = .002), male gender (P less than .001), family history of MACE (P = .03), personal history of hyperlipidemia (P less than .001), and hypertension (P = .04). In contrast, there was no link between MACE and use of NSAIDs. “Similarly, a recent Taiwanese nationwide study did not find an increase in coronary disease in patients taking etoricoxib or celecoxib after adjustment for gender, age, comorbidities, hypertension, hyperlipidemia, and DMARDs,” the researchers wrote.Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
SOURCE: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Risk of major adverse cardiovascular events (MACE) was similar for patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.
Major finding: For every 1,000 patient-years, there were 2.7 MACE for rheumatoid arthritis, 1.4 MACE for axial spondyloarthritis, and 1.4 MACE for psoriatic arthritis. The older age of patients with rheumatoid arthritis explained most of their elevated absolute risk.
Study details: Population-based cohort study of 5,315 patients.
Disclosures: Dr. Lauper reported having no conflicts of interest. The senior author and two coinvestigators disclosed ties to Roche, Abbvie, Pfizer, and several other pharmaceutical companies.
Source: Lauper K et al. Arthritis Care Res. 2018 Apr 2. doi: 10.1002/acr.23567.
Upadacitinib for RA shows encouraging results in phase 3 trial
In a recent phase 3 trial, the investigational oral JAK1 inhibitor upadacitinib met all primary and secondary endpoints in patients with moderate to severe rheumatoid arthritis – including clinical remission – compared with adalimumab and placebo, according to its manufacturer.
The ongoing SELECT-COMPARE trial randomized patients with a stable background on methotrexate but with a limited response to the drug to upadacitinib (n = 651), adalimumab (n = 327), or placebo (n = 651). In terms of primary endpoints, 28% of patients taking upadacitinib achieved remission based on 28-joint Disease Activity Score using C-reactive protein at week 12, compared with 18% of those taking adalimumab and 6% taking placebo. A total of 71% achieved an American College of Rheumatology 20% (ACR20) level of response, compared with 63% of those taking adalimumab and 36% of those taking placebo.
In addition, upadacitinib met the ranked secondary endpoints, showing superiority over adalimumab. It did so in terms of ACR50 and ACR70 at week 12, as well as reduction in patient pain scores and improvement in physical function at week 12. Furthermore, it significantly inhibited radiographic progression.
The safety profile was consistent with previous findings: By week 26, 3.7% of patients taking upadacitinib experienced serious adverse events, compared with 4.3% of patients taking adalimumab and 2.9% of those taking placebo.
Find out more in AbbVie’s press release.
In a recent phase 3 trial, the investigational oral JAK1 inhibitor upadacitinib met all primary and secondary endpoints in patients with moderate to severe rheumatoid arthritis – including clinical remission – compared with adalimumab and placebo, according to its manufacturer.
The ongoing SELECT-COMPARE trial randomized patients with a stable background on methotrexate but with a limited response to the drug to upadacitinib (n = 651), adalimumab (n = 327), or placebo (n = 651). In terms of primary endpoints, 28% of patients taking upadacitinib achieved remission based on 28-joint Disease Activity Score using C-reactive protein at week 12, compared with 18% of those taking adalimumab and 6% taking placebo. A total of 71% achieved an American College of Rheumatology 20% (ACR20) level of response, compared with 63% of those taking adalimumab and 36% of those taking placebo.
In addition, upadacitinib met the ranked secondary endpoints, showing superiority over adalimumab. It did so in terms of ACR50 and ACR70 at week 12, as well as reduction in patient pain scores and improvement in physical function at week 12. Furthermore, it significantly inhibited radiographic progression.
The safety profile was consistent with previous findings: By week 26, 3.7% of patients taking upadacitinib experienced serious adverse events, compared with 4.3% of patients taking adalimumab and 2.9% of those taking placebo.
Find out more in AbbVie’s press release.
In a recent phase 3 trial, the investigational oral JAK1 inhibitor upadacitinib met all primary and secondary endpoints in patients with moderate to severe rheumatoid arthritis – including clinical remission – compared with adalimumab and placebo, according to its manufacturer.
The ongoing SELECT-COMPARE trial randomized patients with a stable background on methotrexate but with a limited response to the drug to upadacitinib (n = 651), adalimumab (n = 327), or placebo (n = 651). In terms of primary endpoints, 28% of patients taking upadacitinib achieved remission based on 28-joint Disease Activity Score using C-reactive protein at week 12, compared with 18% of those taking adalimumab and 6% taking placebo. A total of 71% achieved an American College of Rheumatology 20% (ACR20) level of response, compared with 63% of those taking adalimumab and 36% of those taking placebo.
In addition, upadacitinib met the ranked secondary endpoints, showing superiority over adalimumab. It did so in terms of ACR50 and ACR70 at week 12, as well as reduction in patient pain scores and improvement in physical function at week 12. Furthermore, it significantly inhibited radiographic progression.
The safety profile was consistent with previous findings: By week 26, 3.7% of patients taking upadacitinib experienced serious adverse events, compared with 4.3% of patients taking adalimumab and 2.9% of those taking placebo.
Find out more in AbbVie’s press release.
Dermatology practice gaps: improving medication management
KAUAI, HAWAII – Dermatologists don’t ordinarily peruse the ophthalmology literature. So they may be unaware that the American Academy of Ophthalmology has issued Erik J. Stratman, MD, noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Most dermatologists routinely dose hydroxychloroquine at 400 mg/day, regardless of body weight. The former AAO recommendation, which dates back to 2011, called for dosing at up to 6.5 mg/kg of ideal body weight or 400 mg/day, whichever is lower. However, the AAO recommendation has changed in light of a large, retrospective case-control study that suggested this practice may be overdosing thin patients – thereby exposing them to increased risk of retinal toxicity and other drug-related adverse events – while at the same time possibly underdosing some obese patients, said Dr. Stratman, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
This was one of two dermatology practice gaps he highlighted involving suboptimal medication management, the other being most dermatologists’ failure to protect their patients’ gut when prescribing prednisone.
“I think the push over the last 5 years has been ‘protect the bones, protect the bones, protect the bones.’ We’ve done better and better about protecting the bones and getting that into our conversations with patients on prednisone. But we’re not thinking so much about the gut,” the dermatologist said.
Hydroxychloroquine dosing
The former AAO recommendation was revised in response to a retrospective case-control study of retinal toxicity rates in 2,361 patients on the drug continuously for longer than 5 years. The study demonstrated that the risk of retinopathy jumped 5.7-fold with daily consumption of hydroxychloroquine at more than 5.0 mg/kg (JAMA Ophthalmol. 2014 Dec;132[12]:1453-60).
The current AAO recommendation (Ophthalmology. 2016 Jun;123[6]:1386-94) is to dose hydroxychloroquine at a daily maximum of 5.0 mg/kg of real weight, which correlated better with retinopathy risk in the case-control study than did ideal body weight. Hydroxychloroquine doesn’t accumulate well in fat.
Until now, most dermatologists have not routinely measured patients’ body weight in the office or calculated their body mass index. But Dr. Stratman advised against reliance upon a patient’s self-reported body weight, which may diverge substantially from reality. “Get yourself a good office scale – they’re not that expensive – and use it when prescribing drugs with a tight therapeutic window,” he urged.
Another key to minimizing retinopathy risk in patients on hydroxychloroquine is to pay careful attention to how long they’ve been on the drug. As the years go by in patients being treated for cutaneous lupus or other dermatologic disorders where decades-long therapy is often a mainstay, it’s important to check with patients and make sure they’re getting annual ophthalmologic screening for irreversible retinal toxicity by both threshold visual fields and spectral domain optical coherence tomography. In the large, practice-changing retrospective study, patients on hydroxychloroquine at 4.0-5.0 mg/kg daily had a prevalence of retinopathy of less than 2% during the first 10 years of therapy, but the rate shot up to nearly 20% after 20 years of use, Dr. Stratman observed.
He highlighted as helpful an updated review of the use of hydroxychloroquine in dermatology recently published by Anthony P. Fernandez, MD, PhD, of the department of dermatology at the Cleveland Clinic (J Am Acad Dermatol. 2017 Jun;76[6]:1176-82).
Dr. Fernandez recommends following the AAO guidance to dose the drug at 5.0 mg/kg or less of actual body weight in thin or normal-weight patients; however, he departed from the ophthalmologists with regard to treatment of obese patients. Because dosing based on actual weight could potentially lead to relative overdosing in obese patients, in that growing population he recommends calculating the dose based upon 5.0 mg/kg of actual body weight, as well as the dose based on 6.5 mg/kg of ideal body weight, then prescribing the lower of the two, up to a maximum of 400 mg/day.
“The current recommendation is really about not overdosing thin patients. Basically, dosing is not so difficult for obese people because if you weigh more than 175 pounds, you’re going to get 400 mg/day,” Dr. Stratman explained.
That 400 mg/day ceiling is not cast in stone, he continued. The guideline recommends that, if a patient is a nonresponder to several months of hydroxychloroquine at 400 mg/day, it’s worthwhile to order a drug blood level. If it’s not above the efficacy threshold of more than 750 ng/mL, it’s appropriate to titrate up.
Protecting against prednisone-induced gastritis
“We underprotect the gut,” Dr. Stratman asserted.
He referred to a recent comprehensive dermatologic review of the prevention and management of glucocorticoid-related side effects, especially the part on peptic ulcer disease (J Am Acad Dermatol. 2017 Jan;76[1]:11-6). This is an issue that heretofore hadn’t been much emphasized in the dermatology literature.
“I read this and thought, ‘Gosh, I’m not really having a conversation with my patients about a review of systems for gut protection as I should. And I certainly haven’t been thinking about prescribing PPIs [proton pump inhibitors] for my patients,’” he recalled.
Dr. Stratman polled his Hawaii Dermatology Seminar audience as to who had ever prescribed a PPI. Most indicated with their electronic clickers that they had never done so.
“This is what a practice gap is,” he commented. “You read the literature and you say, ‘Oh, I guess that makes sense. Maybe I should be doing that more often, or making sure it gets done.’”
“I don’t want to come across as saying, ‘For everybody we put on prednisone we should be giving vitamin D, calcium, and a PPI.’ That’s not the message. The message is, assess your patient – or make sure your patient is being assessed – for risk of peptic ulcer disease. And if you don’t feel comfortable prescribing a PPI, please get the patient connected with their primary care provider, who should,” Dr. Stratman said.
The authors of the dermatology review made a case for screening for GI risk factors in every patient who is going to receive an oral glucocorticoid. The ones who absolutely should be prescribed a PPI unless contraindicated include patients who are taking daily aspirin or NSAIDs for an essential reason, such as cardiovascular protection or significant arthritic pain. The authors suggest consideration of a PPI in patients with other, less potent risk factors for peptic ulcer disease, including a history of ulcer disease, gastroesophageal reflux disease, Barrett’s esophagus, heavy smoking, heavy alcohol consumption, age greater than 65, and concomitant use of other medications with an associated risk of peptic ulcer disease – such as bisphosphonates, “which you may have just put them on to protect their bones,” Dr. Stratman noted.
Of course, PPIs come with side effects of their own, including increased fracture risk, Clostridium difficile infections, and rebound acid secretion.
Dr. Stratman reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Dermatologists don’t ordinarily peruse the ophthalmology literature. So they may be unaware that the American Academy of Ophthalmology has issued Erik J. Stratman, MD, noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Most dermatologists routinely dose hydroxychloroquine at 400 mg/day, regardless of body weight. The former AAO recommendation, which dates back to 2011, called for dosing at up to 6.5 mg/kg of ideal body weight or 400 mg/day, whichever is lower. However, the AAO recommendation has changed in light of a large, retrospective case-control study that suggested this practice may be overdosing thin patients – thereby exposing them to increased risk of retinal toxicity and other drug-related adverse events – while at the same time possibly underdosing some obese patients, said Dr. Stratman, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
This was one of two dermatology practice gaps he highlighted involving suboptimal medication management, the other being most dermatologists’ failure to protect their patients’ gut when prescribing prednisone.
“I think the push over the last 5 years has been ‘protect the bones, protect the bones, protect the bones.’ We’ve done better and better about protecting the bones and getting that into our conversations with patients on prednisone. But we’re not thinking so much about the gut,” the dermatologist said.
Hydroxychloroquine dosing
The former AAO recommendation was revised in response to a retrospective case-control study of retinal toxicity rates in 2,361 patients on the drug continuously for longer than 5 years. The study demonstrated that the risk of retinopathy jumped 5.7-fold with daily consumption of hydroxychloroquine at more than 5.0 mg/kg (JAMA Ophthalmol. 2014 Dec;132[12]:1453-60).
The current AAO recommendation (Ophthalmology. 2016 Jun;123[6]:1386-94) is to dose hydroxychloroquine at a daily maximum of 5.0 mg/kg of real weight, which correlated better with retinopathy risk in the case-control study than did ideal body weight. Hydroxychloroquine doesn’t accumulate well in fat.
Until now, most dermatologists have not routinely measured patients’ body weight in the office or calculated their body mass index. But Dr. Stratman advised against reliance upon a patient’s self-reported body weight, which may diverge substantially from reality. “Get yourself a good office scale – they’re not that expensive – and use it when prescribing drugs with a tight therapeutic window,” he urged.
Another key to minimizing retinopathy risk in patients on hydroxychloroquine is to pay careful attention to how long they’ve been on the drug. As the years go by in patients being treated for cutaneous lupus or other dermatologic disorders where decades-long therapy is often a mainstay, it’s important to check with patients and make sure they’re getting annual ophthalmologic screening for irreversible retinal toxicity by both threshold visual fields and spectral domain optical coherence tomography. In the large, practice-changing retrospective study, patients on hydroxychloroquine at 4.0-5.0 mg/kg daily had a prevalence of retinopathy of less than 2% during the first 10 years of therapy, but the rate shot up to nearly 20% after 20 years of use, Dr. Stratman observed.
He highlighted as helpful an updated review of the use of hydroxychloroquine in dermatology recently published by Anthony P. Fernandez, MD, PhD, of the department of dermatology at the Cleveland Clinic (J Am Acad Dermatol. 2017 Jun;76[6]:1176-82).
Dr. Fernandez recommends following the AAO guidance to dose the drug at 5.0 mg/kg or less of actual body weight in thin or normal-weight patients; however, he departed from the ophthalmologists with regard to treatment of obese patients. Because dosing based on actual weight could potentially lead to relative overdosing in obese patients, in that growing population he recommends calculating the dose based upon 5.0 mg/kg of actual body weight, as well as the dose based on 6.5 mg/kg of ideal body weight, then prescribing the lower of the two, up to a maximum of 400 mg/day.
“The current recommendation is really about not overdosing thin patients. Basically, dosing is not so difficult for obese people because if you weigh more than 175 pounds, you’re going to get 400 mg/day,” Dr. Stratman explained.
That 400 mg/day ceiling is not cast in stone, he continued. The guideline recommends that, if a patient is a nonresponder to several months of hydroxychloroquine at 400 mg/day, it’s worthwhile to order a drug blood level. If it’s not above the efficacy threshold of more than 750 ng/mL, it’s appropriate to titrate up.
Protecting against prednisone-induced gastritis
“We underprotect the gut,” Dr. Stratman asserted.
He referred to a recent comprehensive dermatologic review of the prevention and management of glucocorticoid-related side effects, especially the part on peptic ulcer disease (J Am Acad Dermatol. 2017 Jan;76[1]:11-6). This is an issue that heretofore hadn’t been much emphasized in the dermatology literature.
“I read this and thought, ‘Gosh, I’m not really having a conversation with my patients about a review of systems for gut protection as I should. And I certainly haven’t been thinking about prescribing PPIs [proton pump inhibitors] for my patients,’” he recalled.
Dr. Stratman polled his Hawaii Dermatology Seminar audience as to who had ever prescribed a PPI. Most indicated with their electronic clickers that they had never done so.
“This is what a practice gap is,” he commented. “You read the literature and you say, ‘Oh, I guess that makes sense. Maybe I should be doing that more often, or making sure it gets done.’”
“I don’t want to come across as saying, ‘For everybody we put on prednisone we should be giving vitamin D, calcium, and a PPI.’ That’s not the message. The message is, assess your patient – or make sure your patient is being assessed – for risk of peptic ulcer disease. And if you don’t feel comfortable prescribing a PPI, please get the patient connected with their primary care provider, who should,” Dr. Stratman said.
The authors of the dermatology review made a case for screening for GI risk factors in every patient who is going to receive an oral glucocorticoid. The ones who absolutely should be prescribed a PPI unless contraindicated include patients who are taking daily aspirin or NSAIDs for an essential reason, such as cardiovascular protection or significant arthritic pain. The authors suggest consideration of a PPI in patients with other, less potent risk factors for peptic ulcer disease, including a history of ulcer disease, gastroesophageal reflux disease, Barrett’s esophagus, heavy smoking, heavy alcohol consumption, age greater than 65, and concomitant use of other medications with an associated risk of peptic ulcer disease – such as bisphosphonates, “which you may have just put them on to protect their bones,” Dr. Stratman noted.
Of course, PPIs come with side effects of their own, including increased fracture risk, Clostridium difficile infections, and rebound acid secretion.
Dr. Stratman reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
KAUAI, HAWAII – Dermatologists don’t ordinarily peruse the ophthalmology literature. So they may be unaware that the American Academy of Ophthalmology has issued Erik J. Stratman, MD, noted at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
Most dermatologists routinely dose hydroxychloroquine at 400 mg/day, regardless of body weight. The former AAO recommendation, which dates back to 2011, called for dosing at up to 6.5 mg/kg of ideal body weight or 400 mg/day, whichever is lower. However, the AAO recommendation has changed in light of a large, retrospective case-control study that suggested this practice may be overdosing thin patients – thereby exposing them to increased risk of retinal toxicity and other drug-related adverse events – while at the same time possibly underdosing some obese patients, said Dr. Stratman, chairman of the department of dermatology at the Marshfield (Wisc.) Clinic.
This was one of two dermatology practice gaps he highlighted involving suboptimal medication management, the other being most dermatologists’ failure to protect their patients’ gut when prescribing prednisone.
“I think the push over the last 5 years has been ‘protect the bones, protect the bones, protect the bones.’ We’ve done better and better about protecting the bones and getting that into our conversations with patients on prednisone. But we’re not thinking so much about the gut,” the dermatologist said.
Hydroxychloroquine dosing
The former AAO recommendation was revised in response to a retrospective case-control study of retinal toxicity rates in 2,361 patients on the drug continuously for longer than 5 years. The study demonstrated that the risk of retinopathy jumped 5.7-fold with daily consumption of hydroxychloroquine at more than 5.0 mg/kg (JAMA Ophthalmol. 2014 Dec;132[12]:1453-60).
The current AAO recommendation (Ophthalmology. 2016 Jun;123[6]:1386-94) is to dose hydroxychloroquine at a daily maximum of 5.0 mg/kg of real weight, which correlated better with retinopathy risk in the case-control study than did ideal body weight. Hydroxychloroquine doesn’t accumulate well in fat.
Until now, most dermatologists have not routinely measured patients’ body weight in the office or calculated their body mass index. But Dr. Stratman advised against reliance upon a patient’s self-reported body weight, which may diverge substantially from reality. “Get yourself a good office scale – they’re not that expensive – and use it when prescribing drugs with a tight therapeutic window,” he urged.
Another key to minimizing retinopathy risk in patients on hydroxychloroquine is to pay careful attention to how long they’ve been on the drug. As the years go by in patients being treated for cutaneous lupus or other dermatologic disorders where decades-long therapy is often a mainstay, it’s important to check with patients and make sure they’re getting annual ophthalmologic screening for irreversible retinal toxicity by both threshold visual fields and spectral domain optical coherence tomography. In the large, practice-changing retrospective study, patients on hydroxychloroquine at 4.0-5.0 mg/kg daily had a prevalence of retinopathy of less than 2% during the first 10 years of therapy, but the rate shot up to nearly 20% after 20 years of use, Dr. Stratman observed.
He highlighted as helpful an updated review of the use of hydroxychloroquine in dermatology recently published by Anthony P. Fernandez, MD, PhD, of the department of dermatology at the Cleveland Clinic (J Am Acad Dermatol. 2017 Jun;76[6]:1176-82).
Dr. Fernandez recommends following the AAO guidance to dose the drug at 5.0 mg/kg or less of actual body weight in thin or normal-weight patients; however, he departed from the ophthalmologists with regard to treatment of obese patients. Because dosing based on actual weight could potentially lead to relative overdosing in obese patients, in that growing population he recommends calculating the dose based upon 5.0 mg/kg of actual body weight, as well as the dose based on 6.5 mg/kg of ideal body weight, then prescribing the lower of the two, up to a maximum of 400 mg/day.
“The current recommendation is really about not overdosing thin patients. Basically, dosing is not so difficult for obese people because if you weigh more than 175 pounds, you’re going to get 400 mg/day,” Dr. Stratman explained.
That 400 mg/day ceiling is not cast in stone, he continued. The guideline recommends that, if a patient is a nonresponder to several months of hydroxychloroquine at 400 mg/day, it’s worthwhile to order a drug blood level. If it’s not above the efficacy threshold of more than 750 ng/mL, it’s appropriate to titrate up.
Protecting against prednisone-induced gastritis
“We underprotect the gut,” Dr. Stratman asserted.
He referred to a recent comprehensive dermatologic review of the prevention and management of glucocorticoid-related side effects, especially the part on peptic ulcer disease (J Am Acad Dermatol. 2017 Jan;76[1]:11-6). This is an issue that heretofore hadn’t been much emphasized in the dermatology literature.
“I read this and thought, ‘Gosh, I’m not really having a conversation with my patients about a review of systems for gut protection as I should. And I certainly haven’t been thinking about prescribing PPIs [proton pump inhibitors] for my patients,’” he recalled.
Dr. Stratman polled his Hawaii Dermatology Seminar audience as to who had ever prescribed a PPI. Most indicated with their electronic clickers that they had never done so.
“This is what a practice gap is,” he commented. “You read the literature and you say, ‘Oh, I guess that makes sense. Maybe I should be doing that more often, or making sure it gets done.’”
“I don’t want to come across as saying, ‘For everybody we put on prednisone we should be giving vitamin D, calcium, and a PPI.’ That’s not the message. The message is, assess your patient – or make sure your patient is being assessed – for risk of peptic ulcer disease. And if you don’t feel comfortable prescribing a PPI, please get the patient connected with their primary care provider, who should,” Dr. Stratman said.
The authors of the dermatology review made a case for screening for GI risk factors in every patient who is going to receive an oral glucocorticoid. The ones who absolutely should be prescribed a PPI unless contraindicated include patients who are taking daily aspirin or NSAIDs for an essential reason, such as cardiovascular protection or significant arthritic pain. The authors suggest consideration of a PPI in patients with other, less potent risk factors for peptic ulcer disease, including a history of ulcer disease, gastroesophageal reflux disease, Barrett’s esophagus, heavy smoking, heavy alcohol consumption, age greater than 65, and concomitant use of other medications with an associated risk of peptic ulcer disease – such as bisphosphonates, “which you may have just put them on to protect their bones,” Dr. Stratman noted.
Of course, PPIs come with side effects of their own, including increased fracture risk, Clostridium difficile infections, and rebound acid secretion.
Dr. Stratman reported having no financial conflicts regarding his presentation.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
AbbVie, Samsung Bioepis settle suits with delayed U.S. entry for adalimumab biosimilar
A new adalimumab biosimilar will become available in the European Union later this year, but a court settlement will keep Samsung Bioepis’ competitor off U.S. shelves until 2023.
Under the settlement, AbbVie, which manufactures adalimumab (Humira), will grant Bioepis and its partner, Biogen, a nonexclusive license to the intellectual property relating to the antibody. Bioepis’ version, dubbed SB5 (Imraldi), will enter global markets in a staggered fashion, according to an AbbVie press statement. In most countries in the European Union, the license period will begin on Oct. 16, 2018. In the United States, Samsung Bioepis’ license period will begin on June 30, 2023, according to the Abbvie statement.
Biogen and Bioepis hailed the settlement as a victory, but Imraldi won’t be the first Humira biosimilar to break into the U.S. market. Last September, AbbVie settled a similar suit with Amgen, granting patent licenses for the global use and sale of its anti–tumor necrosis factor–alpha antibody, Amgevita/Amjevita. Amgen expects to launch Amgevita in Europe on Oct. 16, 2018, and Amjevita in the United States on Jan. 31, 2023. Samsung Bioepis’ U.S. license date will not be accelerated upon Amgen’s entry.
Ian Henshaw, Biogen’s global head of biosimilars, said the deal further strengthens the company’s European biosimilars reach.
“Biogen is a leader in the emerging field of biosimilars through Samsung Bioepis, our joint venture with Samsung BioLogics,” Mr. Henshaw said in a press statement. “Biogen already markets two biosimilars in Europe and the planned introduction of Imraldi on Oct. 16 could potentially expand patient choice by offering physicians more options to meet the needs of patients while delivering significant savings to healthcare systems.”
AbbVie focused on the settlement as a global recognition of its leadership role in developing the anti-TNF-alpha antibody.
“The Samsung Bioepis settlement reflects the strength and breadth of AbbVie’s intellectual property,” Laura Schumacher, the company’s general counsel, said in the Abbvie statement. “We continue to believe biosimilars will play an important role in our healthcare system, but we also believe it is important to protect our investment in innovation. This agreement accomplishes both objectives.”
Samsung Bioepis will pay royalties to AbbVie for licensing its adalimumab patents once its biosimilar product is launched. As is the case with the prior Amgen resolution, AbbVie will not make any payments to Samsung Bioepis. “All litigation pending between the parties, as well as all litigation with Samsung Bioepis’ European partner, Biogen, will be dismissed. The precise terms of the agreements are confidential,” the Abbvie statement said.
The settlement brings to a closing a flurry of lawsuits Samsung Bioepis filed against AbbVie in 2017.
A new adalimumab biosimilar will become available in the European Union later this year, but a court settlement will keep Samsung Bioepis’ competitor off U.S. shelves until 2023.
Under the settlement, AbbVie, which manufactures adalimumab (Humira), will grant Bioepis and its partner, Biogen, a nonexclusive license to the intellectual property relating to the antibody. Bioepis’ version, dubbed SB5 (Imraldi), will enter global markets in a staggered fashion, according to an AbbVie press statement. In most countries in the European Union, the license period will begin on Oct. 16, 2018. In the United States, Samsung Bioepis’ license period will begin on June 30, 2023, according to the Abbvie statement.
Biogen and Bioepis hailed the settlement as a victory, but Imraldi won’t be the first Humira biosimilar to break into the U.S. market. Last September, AbbVie settled a similar suit with Amgen, granting patent licenses for the global use and sale of its anti–tumor necrosis factor–alpha antibody, Amgevita/Amjevita. Amgen expects to launch Amgevita in Europe on Oct. 16, 2018, and Amjevita in the United States on Jan. 31, 2023. Samsung Bioepis’ U.S. license date will not be accelerated upon Amgen’s entry.
Ian Henshaw, Biogen’s global head of biosimilars, said the deal further strengthens the company’s European biosimilars reach.
“Biogen is a leader in the emerging field of biosimilars through Samsung Bioepis, our joint venture with Samsung BioLogics,” Mr. Henshaw said in a press statement. “Biogen already markets two biosimilars in Europe and the planned introduction of Imraldi on Oct. 16 could potentially expand patient choice by offering physicians more options to meet the needs of patients while delivering significant savings to healthcare systems.”
AbbVie focused on the settlement as a global recognition of its leadership role in developing the anti-TNF-alpha antibody.
“The Samsung Bioepis settlement reflects the strength and breadth of AbbVie’s intellectual property,” Laura Schumacher, the company’s general counsel, said in the Abbvie statement. “We continue to believe biosimilars will play an important role in our healthcare system, but we also believe it is important to protect our investment in innovation. This agreement accomplishes both objectives.”
Samsung Bioepis will pay royalties to AbbVie for licensing its adalimumab patents once its biosimilar product is launched. As is the case with the prior Amgen resolution, AbbVie will not make any payments to Samsung Bioepis. “All litigation pending between the parties, as well as all litigation with Samsung Bioepis’ European partner, Biogen, will be dismissed. The precise terms of the agreements are confidential,” the Abbvie statement said.
The settlement brings to a closing a flurry of lawsuits Samsung Bioepis filed against AbbVie in 2017.
A new adalimumab biosimilar will become available in the European Union later this year, but a court settlement will keep Samsung Bioepis’ competitor off U.S. shelves until 2023.
Under the settlement, AbbVie, which manufactures adalimumab (Humira), will grant Bioepis and its partner, Biogen, a nonexclusive license to the intellectual property relating to the antibody. Bioepis’ version, dubbed SB5 (Imraldi), will enter global markets in a staggered fashion, according to an AbbVie press statement. In most countries in the European Union, the license period will begin on Oct. 16, 2018. In the United States, Samsung Bioepis’ license period will begin on June 30, 2023, according to the Abbvie statement.
Biogen and Bioepis hailed the settlement as a victory, but Imraldi won’t be the first Humira biosimilar to break into the U.S. market. Last September, AbbVie settled a similar suit with Amgen, granting patent licenses for the global use and sale of its anti–tumor necrosis factor–alpha antibody, Amgevita/Amjevita. Amgen expects to launch Amgevita in Europe on Oct. 16, 2018, and Amjevita in the United States on Jan. 31, 2023. Samsung Bioepis’ U.S. license date will not be accelerated upon Amgen’s entry.
Ian Henshaw, Biogen’s global head of biosimilars, said the deal further strengthens the company’s European biosimilars reach.
“Biogen is a leader in the emerging field of biosimilars through Samsung Bioepis, our joint venture with Samsung BioLogics,” Mr. Henshaw said in a press statement. “Biogen already markets two biosimilars in Europe and the planned introduction of Imraldi on Oct. 16 could potentially expand patient choice by offering physicians more options to meet the needs of patients while delivering significant savings to healthcare systems.”
AbbVie focused on the settlement as a global recognition of its leadership role in developing the anti-TNF-alpha antibody.
“The Samsung Bioepis settlement reflects the strength and breadth of AbbVie’s intellectual property,” Laura Schumacher, the company’s general counsel, said in the Abbvie statement. “We continue to believe biosimilars will play an important role in our healthcare system, but we also believe it is important to protect our investment in innovation. This agreement accomplishes both objectives.”
Samsung Bioepis will pay royalties to AbbVie for licensing its adalimumab patents once its biosimilar product is launched. As is the case with the prior Amgen resolution, AbbVie will not make any payments to Samsung Bioepis. “All litigation pending between the parties, as well as all litigation with Samsung Bioepis’ European partner, Biogen, will be dismissed. The precise terms of the agreements are confidential,” the Abbvie statement said.
The settlement brings to a closing a flurry of lawsuits Samsung Bioepis filed against AbbVie in 2017.
Reassurance for women taking certolizumab during pregnancy
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
according to results of a new study.
Megan E.B. Clowse, MD, of Duke University Medical Center, Durham, N.C., and her coauthors reported on a prospective and retrospective analysis of data from 528 pregnancies – including 10 twin pregnancies – in which the mother was exposed to the anti–tumor necrosis factor (anti-TNF) drug certolizumab during pregnancy.
There were 459 (85.3%) live births, 47 (8.7%) miscarriages, 27 (5%) elective abortions, and five (0.9%) stillbirths, figures that are similar to those seen in the general population. Among the singleton births, 11.7% were low birth weight, which the authors noted was slightly higher than the frequency observed in the general population but was in line with previous reports with TNF inhibitors.
Two cases of neonatal death were reported. One occurred in one member of a female twin pair, born at 25 weeks, who succumbed to brain damage and pneumoperitoneum. The other was also in female twins, born at 27 weeks, in which one of the pair was born with a heart defect and died during surgery for an unspecified infection of the intestines, the authors reported in Arthritis & Rheumatology.
The study noted eight (1.7%) reports of congenital malformations in the infants born alive, including accessory auricle, polydactyly, hydronephrosis, cerebral ventricle dilatation, and congenital heart disease.
Four cases were in infants whose mothers had rheumatoid arthritis, one in an infant whose mother had ankylosing spondylitis, and three in infants whose mothers had Crohn’s disease (CD).
In five cases, the women were exposed to certolizumab at least in the first trimester, in four they were exposed at least in the second trimester, and in five cases, the women were exposed at least during the third trimester of pregnancy.
“The teratologist review concluded no temporal association with CZP [certolizumab] exposure for the case of hydronephrosis, owing to evidence of anomalies on ultrasound prior to initiation of medication (during the third trimester); the possibility of an association could not be ruled out for the cases of anal fistula, accessory auricle, vesicoureteric reflux, talipes, and congenital heart disease,” the researchers wrote.
Twenty-two women (4.2%) had serious infections during pregnancy, which was in line with the frequency of serious infections reported in patients taking certolizumab.
Among the live births, nearly half (44.5%) reported certolizumab exposure during all three trimesters, 81.2% reported exposure at least during the first trimester, and 29.2% were exposed during the first trimester only.
“More women with rheumatic diseases than CD had first-trimester–only or first- and second-trimester exposure to CZP, reflecting the differing clinical practice between CD and rheumatic diseases,” the authors wrote. “Spontaneous disease improvement in women with IBD [inflammatory bowel disease] during pregnancy is less likely, compared to RA and other rheumatic diseases, and many patients may require treatment throughout pregnancy; thus, potentially reducing the risk of adverse outcomes, such as spontaneous miscarriage, premature birth, low birth weight, small gestational age.”
The authors commented that, despite increasing evidence of the safety of TNF inhibitors during pregnancy – recent systematic reviews and meta-analyses have found no link to adverse outcomes with anti-TNF exposure during the first trimester – patients and physicians still have had concerns about their use.
“This analysis of prospective pregnancy reports from the UCB Pharma safety database represents the largest published cohort of pregnant women exposed to an anti-TNF for the management of chronic inflammatory diseases,” the authors wrote. “It addresses the need for new and detailed studies on the impact of drug exposure during pregnancy and supports the conclusion that CZP exposure in utero does not appear to increase the risk of major congenital malformations or fetal loss.”
However, they acknowledged the lack of an untreated control group and said this meant a formal statistical analysis was not possible. They also noted that outcomes data were not available for about one-third of the entire cohort of 1,137 women whose pregnancies were exposed to certolizumab.
“However, these data are reassuring for women of childbearing age affected by chronic inflammatory diseases who need an anti-TNF to control their condition and wish to become or are pregnant during CZP treatment,” they wrote.
The study was funded by UCB Pharma. One author was a contractor for, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
SOURCE: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point: Certolizumab use during pregnancy does not appear to increase the risk of congenital malformations.
Major finding: The incidence of fetal death and congenital malformations in certolizumab-exposed pregnancies is similar to that in the general population.
Study details: A prospective and retrospective analysis of data from 528 certolizumab-exposed pregnancies.
Disclosures: The study was funded by UCB Pharma. One author was a contractor for UCB Pharma, and three were employees of, UCB Pharma. Six authors declared grants, consulting fees, and other remuneration from pharmaceutical companies, including UCB Pharma.
Source: Clowse MEB et al. Arthritis & Rheumatology. 2018 Apr 5. doi: 10.1002/art.40508
2018 FNIH Lurie Prize awarded for DNA immune response discovery
The Foundation of the National Institutes of Health has awarded according to a statement released Tuesday, April 3.
“We are proud to honor Dr. Chen with the 2018 Lurie Prize in Biomedical Sciences for the discovery of the cGAS enzyme and pathway and their unique role in immune and inflammatory response,” Maria C. Freire, PhD, president and executive director of the FNIH, said in a press release. “Dr. Chen joins five other Lurie Prize winners, who are shaping the future of human health through their profound biomedical research.”
While scientists have known for some time that DNA had a role in activating the immune response, the specifics of the process eluded explanation.
Through their work, Dr. Chen and his team uncovered that cGAS was the enzyme used to spark the reaction.
“[cGAS] is a protein sensor that detects DNA as a danger signal that then triggers the immune response,” said Dr. Chen. “When DNA gets into the cytoplasm, cGAS becomes activated and catalyzes the synthesis of a small molecule, called cGAMP, which then functions as a messenger that activates the immune response pathway.”
While the cGAS enzyme can help defend against infectious disease or cancer, the enzyme can also trigger autoimmune diseases such as rheumatoid arthritis.
Dr. Chen is the George L. MacGregor Distinguished Chair in Biomedical Science and professor of molecular biology at the University of Texas Southwestern Medical Center, Dallas, and an investigator for the Howard Hughes Medical Institute, Chevy Chase, Md. He completed his undergraduate study in biology at Fujian (China) Normal University, after which he went on to earn his PhD from State University of New York at Buffalo.
The prize includes a $100,000 honorarium, donated to the FNIH by philanthropist Ann Lurie, who serves as president of the Ann and Robert H. Lurie Foundation and president of Lurie Holdings, according to the press release.
“This is a tremendous honor and is a strong endorsement of the work discovered by the scientists in my lab; it is very exciting,” said Dr. Chen. “We hope to continue our work to deepen our understanding of this pathway, as the mechanisms of the pathway are not yet completely understood, as well as look more into how we can harness the immunity pathway to develop treatments for cases like autoimmune diseases or cancer.”
The Foundation of the National Institutes of Health has awarded according to a statement released Tuesday, April 3.
“We are proud to honor Dr. Chen with the 2018 Lurie Prize in Biomedical Sciences for the discovery of the cGAS enzyme and pathway and their unique role in immune and inflammatory response,” Maria C. Freire, PhD, president and executive director of the FNIH, said in a press release. “Dr. Chen joins five other Lurie Prize winners, who are shaping the future of human health through their profound biomedical research.”
While scientists have known for some time that DNA had a role in activating the immune response, the specifics of the process eluded explanation.
Through their work, Dr. Chen and his team uncovered that cGAS was the enzyme used to spark the reaction.
“[cGAS] is a protein sensor that detects DNA as a danger signal that then triggers the immune response,” said Dr. Chen. “When DNA gets into the cytoplasm, cGAS becomes activated and catalyzes the synthesis of a small molecule, called cGAMP, which then functions as a messenger that activates the immune response pathway.”
While the cGAS enzyme can help defend against infectious disease or cancer, the enzyme can also trigger autoimmune diseases such as rheumatoid arthritis.
Dr. Chen is the George L. MacGregor Distinguished Chair in Biomedical Science and professor of molecular biology at the University of Texas Southwestern Medical Center, Dallas, and an investigator for the Howard Hughes Medical Institute, Chevy Chase, Md. He completed his undergraduate study in biology at Fujian (China) Normal University, after which he went on to earn his PhD from State University of New York at Buffalo.
The prize includes a $100,000 honorarium, donated to the FNIH by philanthropist Ann Lurie, who serves as president of the Ann and Robert H. Lurie Foundation and president of Lurie Holdings, according to the press release.
“This is a tremendous honor and is a strong endorsement of the work discovered by the scientists in my lab; it is very exciting,” said Dr. Chen. “We hope to continue our work to deepen our understanding of this pathway, as the mechanisms of the pathway are not yet completely understood, as well as look more into how we can harness the immunity pathway to develop treatments for cases like autoimmune diseases or cancer.”
The Foundation of the National Institutes of Health has awarded according to a statement released Tuesday, April 3.
“We are proud to honor Dr. Chen with the 2018 Lurie Prize in Biomedical Sciences for the discovery of the cGAS enzyme and pathway and their unique role in immune and inflammatory response,” Maria C. Freire, PhD, president and executive director of the FNIH, said in a press release. “Dr. Chen joins five other Lurie Prize winners, who are shaping the future of human health through their profound biomedical research.”
While scientists have known for some time that DNA had a role in activating the immune response, the specifics of the process eluded explanation.
Through their work, Dr. Chen and his team uncovered that cGAS was the enzyme used to spark the reaction.
“[cGAS] is a protein sensor that detects DNA as a danger signal that then triggers the immune response,” said Dr. Chen. “When DNA gets into the cytoplasm, cGAS becomes activated and catalyzes the synthesis of a small molecule, called cGAMP, which then functions as a messenger that activates the immune response pathway.”
While the cGAS enzyme can help defend against infectious disease or cancer, the enzyme can also trigger autoimmune diseases such as rheumatoid arthritis.
Dr. Chen is the George L. MacGregor Distinguished Chair in Biomedical Science and professor of molecular biology at the University of Texas Southwestern Medical Center, Dallas, and an investigator for the Howard Hughes Medical Institute, Chevy Chase, Md. He completed his undergraduate study in biology at Fujian (China) Normal University, after which he went on to earn his PhD from State University of New York at Buffalo.
The prize includes a $100,000 honorarium, donated to the FNIH by philanthropist Ann Lurie, who serves as president of the Ann and Robert H. Lurie Foundation and president of Lurie Holdings, according to the press release.
“This is a tremendous honor and is a strong endorsement of the work discovered by the scientists in my lab; it is very exciting,” said Dr. Chen. “We hope to continue our work to deepen our understanding of this pathway, as the mechanisms of the pathway are not yet completely understood, as well as look more into how we can harness the immunity pathway to develop treatments for cases like autoimmune diseases or cancer.”
Few acutely ill hospitalized patients receive VTE prophylaxis
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
SAN DIEGO – Among patients hospitalized for acute medical illnesses, the risk of venous thromboembolism (VTE) remained elevated 30-40 days after discharge, results from a large analysis of national data showed.
Moreover, only 7% of at-risk patients received VTE prophylaxis in both the inpatient and outpatient setting.
“The results of this real-world study imply that there is a significantly unmet medical need for effective VTE prophylaxis in both the inpatient and outpatient continuum of care among patients hospitalized for acute medical illnesses,” researchers led by Alpesh Amin, MD, wrote in a poster presented at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
According to Dr. Amin, who chairs the department of medicine at the University of California, Irvine, hospitalized patients with acute medical illnesses face an increased risk for VTE during hospital discharge, mainly within 40 days following hospital admission. However, the treatment patterns of VTE prophylaxis in this patient population have not been well studied in the “real-world” setting. In an effort to improve this area of clinical practice, the researchers used the Marketscan database between Jan. 1, 2012, and June 30, 2015, to identify acutely ill hospitalized patients, such as those with heart failure, respiratory diseases, ischemic stroke, cancer, infectious diseases, and rheumatic diseases. The key outcomes of interest were the proportion of patients receiving inpatient and outpatient VTE prophylaxis and the proportion of patients with VTE events during and after the index hospitalization. They used Kaplan-Meier analysis to examine the risk for VTE events after the index inpatient admission.
The mean age of the 17,895 patients was 58 years, 55% were female, and most (77%) were from the Southern area of the United States. Their mean Charlson Comborbidity Index score prior to hospitalization was 2.2. Nearly all hospitals (87%) were urban based, nonteaching (95%), and large, with 68% having at least 300 beds. Nearly three-quarters of patients (72%) were hospitalized for infectious and respiratory diseases, and the mean length of stay was 5 days.
Dr. Amin and his associates found that 59% of hospitalized patients did not receive any VTE prophylaxis, while only 7% received prophylaxis in both the inpatient and outpatient continuum of care. At the same time, cumulative VTE rates within 40 days of index admission were highest among patients hospitalized for infectious diseases and cancer (3.4% each), followed by those with heart failure (3.1%), respiratory diseases (2%), ischemic stroke (1.5%), and rheumatic diseases (1.3%). The cumulative VTE event rate for the overall study population within 40 days from index hospitalization was nearly 3%, with 60% of VTE events having occurred within 40 days.
The study was funded by Portola Pharmaceuticals. Dr. Amin reported having no financial disclosures.
SOURCE: Amin A et al. THSNA 2018, Poster 51.
REPORTING FROM THSNA 2018
Key clinical point: There is a significant unmet medical need for VTE prophylaxis in the continuum of care of patients hospitalized for acute medical illnesses.
Major finding: Of the overall study population, only 7% received both inpatient and outpatient VTE prophylaxis.
Study details: An analysis of national data from 17,895 acutely ill hospitalized patients.
Disclosures: The study was funded by Portola Pharmaceuticals. The presenter reported having no financial conflicts.
Source: Amin A et al. THSNA 2018, Poster 51.
Certolizumab pegol: Has serious infection risk been overstated?
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
Contrary to prior reports, certolizumab pegol may not be associated with an increased risk of serious infections versus other biologics used in the treatment of rheumatoid arthritis, according to results of a recent U.K. registry study.
Certolizumab pegol (Cimzia) actually had a lower risk of serious infections, compared with etanercept in the primary analysis, according to a report on the study recently published in Annals of the Rheumatic Diseases.
In sensitivity analyses, though, the result in favor of certolizumab pegol was no longer significant, according to lead author Andrew I. Rutherford, MBBS, of King’s College London, and his coauthors.
“From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of [serious infection] than other biologics,” Dr. Rutherford and his colleagues said in their report. “However, the risk does not appear to be significantly higher as has previously been suggested.”
The prospective, observational cohort study, based on data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), represented 19,282 patients with 46,771 years of follow-up, according to the authors.
For the entire cohort, the incidence of serious infections was 5.51 cases per 100 patient-years (95% confidence interval, 5.29-5.71), and the 30-day mortality after serious infection was 10.4% (95% CI, 9.2%-11.6%), the report said. Compared with etanercept, the risk of serious infections was lower for certolizumab pegol (adjusted hazard ratio, 0.75; 95% CI, 0.58-0.97). Etanercept was used as the reference arm for comparison since it was the most widely prescribed drug in the registry.
That finding is in “direct contradiction” to a 2011 Cochrane review finding that certolizumab pegol was associated with an infection rate three to four times higher than other anti–tumor necrosis factor (anti-TNF) drugs (Cochrane Database Syst Rev. 2011;2:Cd008794), the authors noted.
“It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks,” Dr. Rutherford and his coauthors observed in their report.
However, investigators noticed that in the certolizumab pegol cohort, a large number of patients had not previously been on a biologic. When those biologic-naive patients were excluded from analysis, there was no longer a difference in infection rate favoring certolizumab pegol. “This suggests that unmeasured confounders may be responsible for the difference that was observed in the primary analysis,” the investigators said in their discussion of the results.
The Cochrane review showing an increased risk of serious infections with certolizumab pegol was a large network meta-analysis, which they said relies on indirect comparisons between drugs and could be prone to error if there are differences in study design.
“In contrast, national registers use the same methodology for detecting and reporting of adverse events for each drug,” they added.
Dr. Rutherford reported no disclosures. Study coauthors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
SOURCE: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.
FROM ANNALS OF THE RHEUMATIC DISEASES
Key clinical point:
Major finding: Certolizumab pegol had a lower risk of serious infections compared to etanercept (HR, 0.75; 95% CI, 0.58-0.97), though in sensitivity analyses, the difference was no longer significant.
Study details: A prospective observational cohort study of data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) representing 19,282 patients with 46,771 years of follow-up.
Disclosures: Study authors reported disclosures related to Pfizer, AbbVie, Bristol-Myers Squibb, UCB, and Celgene. The British Society for Rheumatology, which commissioned the study, receives income from AbbVie, Celltrion, Hospira, Pfizer, UCB, and Roche related to a different contract.
Source: Rutherford AI et al. Ann Rheum Dis. 2018 Mar 28. doi: 10.1136/annrheumdis-2017-212825.