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FDA urged to bring rheumatologists into gadolinium safety discussion
CHICAGO – The Food and Drug Administration’s updated safety warning about gadolinium-based contrast agents was dismissed as too little, too late during a postsession discussion at the annual meeting of the American College of Rheumatology.
The class warning that “gadolinium is retained for months or years in brain, bone, and other organs,” a directive that a new patient medication guide be given to everyone before receiving a gadolinium-based contrast agent, and a request that manufacturers conduct human and animal studies to further assess the safety of these products, was highlighted at the FDA update session on safety issues in the treatment of rheumatic disease.
The request for further studies grew out of the FDA Advisory Committee on Medical Imaging’s Fall 2017 meeting, which concluded that, “based on available data, there is insufficient evidence of a causal relationship between adverse events and gadolinium retention and recommended the need for additional studies to inform regulatory action,” explained Rachel L. Glaser, MD, a medical officer in the agency’s division of pulmonary, allergy, and rheumatology products and a practicing rheumatologist.
Jonathan Kay, MD, rose from the audience to take the FDA to task for delegating matters related to gadolinium-based contrast agent safety to the radiologists comprising the Advisory Committee on Medical Imaging. “I think the FDA ought to bring this matter to a group of physicians who actually care for patients to get our input on this. Maybe the Arthritis Advisory Committee,” he said.
“It’s been known for more than 15 years that gadolinium deposits in the bone, and for more than 5 years that gadolinium deposits in the brain of patients who’ve received multiple magnetic resonance studies. I’m concerned that the FDA has this issue in the purview of the radiologists because radiologists administer these contrast agents and then don’t see the patients back in follow-up, whereas rheumatologists do,” noted Dr. Kay, professor of medicine and director of clinical research in rheumatology at the University of Massachusetts, Worcester.
He blasted the FDA’s call for further human and animal studies, noting “nephrogenic systemic fibrosis was the human experiment that was done with gadolinium contrast, showing that these agents, when they deposit in tissue, are extremely toxic. I can’t see other human studies being done to determine the potential consequences of these agents when they deposit long term in brain, bone, and other tissues. And the animal studies have already been done demonstrating the danger of these compounds. Might you take this out of the realm of radiologists and involve physicians who take care of patients chronically and observe the long-term consequences of these toxic effects?”
Dr. Glaser responded that the deliberations of the agency’s Advisory Committee on Medical Imaging are reviewed under the purview of the FDA’s Center for Drug Evaluation and Research. “That does include radiologists, but also other clinical reviewers of various backgrounds, including pharmacologists and toxicologists.”
Dr. Kay did not relent, further commenting that he has personally seen “over 150 patients with the devastating consequences of nephrogenic systemic fibrosis.” He added that a prominent radiologist has stated in a public forum that the risk of getting injured from crossing the street is greater than that from getting an MRI with gadolinium. “That’s completely wrong,” he declared.
Dr. Glaser and Dr. Kay reported having no financial conflicts.
CHICAGO – The Food and Drug Administration’s updated safety warning about gadolinium-based contrast agents was dismissed as too little, too late during a postsession discussion at the annual meeting of the American College of Rheumatology.
The class warning that “gadolinium is retained for months or years in brain, bone, and other organs,” a directive that a new patient medication guide be given to everyone before receiving a gadolinium-based contrast agent, and a request that manufacturers conduct human and animal studies to further assess the safety of these products, was highlighted at the FDA update session on safety issues in the treatment of rheumatic disease.
The request for further studies grew out of the FDA Advisory Committee on Medical Imaging’s Fall 2017 meeting, which concluded that, “based on available data, there is insufficient evidence of a causal relationship between adverse events and gadolinium retention and recommended the need for additional studies to inform regulatory action,” explained Rachel L. Glaser, MD, a medical officer in the agency’s division of pulmonary, allergy, and rheumatology products and a practicing rheumatologist.
Jonathan Kay, MD, rose from the audience to take the FDA to task for delegating matters related to gadolinium-based contrast agent safety to the radiologists comprising the Advisory Committee on Medical Imaging. “I think the FDA ought to bring this matter to a group of physicians who actually care for patients to get our input on this. Maybe the Arthritis Advisory Committee,” he said.
“It’s been known for more than 15 years that gadolinium deposits in the bone, and for more than 5 years that gadolinium deposits in the brain of patients who’ve received multiple magnetic resonance studies. I’m concerned that the FDA has this issue in the purview of the radiologists because radiologists administer these contrast agents and then don’t see the patients back in follow-up, whereas rheumatologists do,” noted Dr. Kay, professor of medicine and director of clinical research in rheumatology at the University of Massachusetts, Worcester.
He blasted the FDA’s call for further human and animal studies, noting “nephrogenic systemic fibrosis was the human experiment that was done with gadolinium contrast, showing that these agents, when they deposit in tissue, are extremely toxic. I can’t see other human studies being done to determine the potential consequences of these agents when they deposit long term in brain, bone, and other tissues. And the animal studies have already been done demonstrating the danger of these compounds. Might you take this out of the realm of radiologists and involve physicians who take care of patients chronically and observe the long-term consequences of these toxic effects?”
Dr. Glaser responded that the deliberations of the agency’s Advisory Committee on Medical Imaging are reviewed under the purview of the FDA’s Center for Drug Evaluation and Research. “That does include radiologists, but also other clinical reviewers of various backgrounds, including pharmacologists and toxicologists.”
Dr. Kay did not relent, further commenting that he has personally seen “over 150 patients with the devastating consequences of nephrogenic systemic fibrosis.” He added that a prominent radiologist has stated in a public forum that the risk of getting injured from crossing the street is greater than that from getting an MRI with gadolinium. “That’s completely wrong,” he declared.
Dr. Glaser and Dr. Kay reported having no financial conflicts.
CHICAGO – The Food and Drug Administration’s updated safety warning about gadolinium-based contrast agents was dismissed as too little, too late during a postsession discussion at the annual meeting of the American College of Rheumatology.
The class warning that “gadolinium is retained for months or years in brain, bone, and other organs,” a directive that a new patient medication guide be given to everyone before receiving a gadolinium-based contrast agent, and a request that manufacturers conduct human and animal studies to further assess the safety of these products, was highlighted at the FDA update session on safety issues in the treatment of rheumatic disease.
The request for further studies grew out of the FDA Advisory Committee on Medical Imaging’s Fall 2017 meeting, which concluded that, “based on available data, there is insufficient evidence of a causal relationship between adverse events and gadolinium retention and recommended the need for additional studies to inform regulatory action,” explained Rachel L. Glaser, MD, a medical officer in the agency’s division of pulmonary, allergy, and rheumatology products and a practicing rheumatologist.
Jonathan Kay, MD, rose from the audience to take the FDA to task for delegating matters related to gadolinium-based contrast agent safety to the radiologists comprising the Advisory Committee on Medical Imaging. “I think the FDA ought to bring this matter to a group of physicians who actually care for patients to get our input on this. Maybe the Arthritis Advisory Committee,” he said.
“It’s been known for more than 15 years that gadolinium deposits in the bone, and for more than 5 years that gadolinium deposits in the brain of patients who’ve received multiple magnetic resonance studies. I’m concerned that the FDA has this issue in the purview of the radiologists because radiologists administer these contrast agents and then don’t see the patients back in follow-up, whereas rheumatologists do,” noted Dr. Kay, professor of medicine and director of clinical research in rheumatology at the University of Massachusetts, Worcester.
He blasted the FDA’s call for further human and animal studies, noting “nephrogenic systemic fibrosis was the human experiment that was done with gadolinium contrast, showing that these agents, when they deposit in tissue, are extremely toxic. I can’t see other human studies being done to determine the potential consequences of these agents when they deposit long term in brain, bone, and other tissues. And the animal studies have already been done demonstrating the danger of these compounds. Might you take this out of the realm of radiologists and involve physicians who take care of patients chronically and observe the long-term consequences of these toxic effects?”
Dr. Glaser responded that the deliberations of the agency’s Advisory Committee on Medical Imaging are reviewed under the purview of the FDA’s Center for Drug Evaluation and Research. “That does include radiologists, but also other clinical reviewers of various backgrounds, including pharmacologists and toxicologists.”
Dr. Kay did not relent, further commenting that he has personally seen “over 150 patients with the devastating consequences of nephrogenic systemic fibrosis.” He added that a prominent radiologist has stated in a public forum that the risk of getting injured from crossing the street is greater than that from getting an MRI with gadolinium. “That’s completely wrong,” he declared.
Dr. Glaser and Dr. Kay reported having no financial conflicts.
EXPERT ANALYSIS FROM THE ACR ANNUAL MEETING
Nerve growth factor antibody cuts OA pain with low AEs
CHICAGO – The nerve growth factor antibody tanezumab met its primary efficacy endpoints for improving pain and physical function in patients with knee or hip OA while also showing a low incidence of the drug’s most concerning adverse effect in the first results from a phase 3 study of a drug in this new class.
The placebo-controlled, multicenter study enrolled 696 U.S. OA patients with moderate to severe knee or hip pain and showed that two subcutaneous injections of the humanized antibody tanezumab spaced 8 weeks apart led to statistically significant improvements relative to placebo for pain, physical function, and patient global assessment of OA, Thomas J. Schnitzer, MD, said at the annual meeting of the American College of Rheumatology.
The primary efficacy measurements occurred 8 weeks following the second subcutaneous injection. The study included two active treatment arms, and all the efficacy measures responses showed consistent, “modest” improvements in the patients who received a 2.5 mg injection followed by a 5 mg injection, compared with those who received two 2.5 mg injections.
For the safety analysis the researchers followed patients out to 24 weeks after they received their final injection. The main adverse event of interest was rapidly progressive OA (RPOA), which occurred in five patients who received two 2.5-mg dosages and in one patient who received the 2.5 mg followed by 5 mg regimen; no RPOA occurred among placebo patients. The 1.3% incidence of RPOA among all 494 patients who received tanezumab “aligned with expectations based on the risk mitigation procedures used,” said Dr. Schnitzer, a rheumatologist and professor of medicine, anesthesiology, and physical medicine and rehabilitation at Northwestern University, Chicago. No patient developed primary osteonecrosis.
Two patients who developed RPOA then underwent total joint replacement. The overall rate of total joint replacement was 4 among placebo patients, all involving knees, and 24 among patients treated with tanezumab, including 12 knee replacements and 12 hip replacements. Blinded adjudication determined that 26 of the total 28 joint replacements resulted from “normal” OA progression.
The rates of all adverse events, serious adverse events, and adverse events leading to treatment discontinuation were low and similar in the three treatment arms.
Earlier clinical studies of tanezumab had signaled a problem with RPOA (Arthritis Rheumatol. 2016 Feb;68[2]:382-91), which led the Food and Drug Administration to order a temporary halt to clinical testing of all nerve growth factor antagonists in 2010 that the agency then lifted in 2015 (Clin Exp Rheumatol. 2017 Sept-Oct;35[suppl 107]:85-7). In 2017, the FDA gave clinical development of tanezumab “fast-track” status. The results that Dr. Schnitzer reported represent the first outcomes from several phase 3 studies that the companies developing tanezumab are now running and that collectively include about 7,000 total patients, according to a written statement from the developing companies. The companies released an initial statement about the current results in July 2018.
The study reported by Dr. Schnitzer enrolled patients with OA of the knee or hip at several U.S. sites. For the primary endpoint of mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the results at 16 weeks were –2.6 units in the placebo patients and –3.4 units among patients who received the higher dosage. For the primary outcome of mean change in WOMAC physical function score, the results were –2.6 in the placebo arm and –3.5 in patients on the higher dosage. For the primary outcome of change in patient’s global assessment of their OA, the results were –0.65 in the placebo patients and –0.90 in those on the highest dosage. All three between-group differences were statistically significant.
A key secondary outcome was the percentage of patients having at least a 50% reduction in their WOMAC pain score, which occurred in 38% of the placebo patients and in 57% on the higher tanezumab dosage, a statistically significant difference, Dr. Schnitzer reported. A final efficacy finding was the percentage of patients who had a 50% or greater pain reduction at week 16 who did not have a pain response at week 8, a parameter that could reflect incremental benefit from the larger, second tanezumab dose. This outcome occurred in 19% of placebo patients and in 22% of patients who received two 2.5-mg doses of tanezumab; among those who received a 5-mg dose after the first 2.5-mg dose, the rate was 33%.
The study was sponsored by Eli Lilly and Pfizer, the companies jointly developing tanezumab. Dr. Schnitzer has been a consultant to and has received research support from Eli Lilly and Pfizer. He has also been a consultant to AbbVie, Aptinyx, Genzyme, Regeneron, and Vertex Pharmaceuticals, and has received research support from Grünenthal and Radius Health.
SOURCE: Schnitzer TJ et al. Arthritis Rheumatol. 2018;70(Suppl 10) Abstract L20.
CHICAGO – The nerve growth factor antibody tanezumab met its primary efficacy endpoints for improving pain and physical function in patients with knee or hip OA while also showing a low incidence of the drug’s most concerning adverse effect in the first results from a phase 3 study of a drug in this new class.
The placebo-controlled, multicenter study enrolled 696 U.S. OA patients with moderate to severe knee or hip pain and showed that two subcutaneous injections of the humanized antibody tanezumab spaced 8 weeks apart led to statistically significant improvements relative to placebo for pain, physical function, and patient global assessment of OA, Thomas J. Schnitzer, MD, said at the annual meeting of the American College of Rheumatology.
The primary efficacy measurements occurred 8 weeks following the second subcutaneous injection. The study included two active treatment arms, and all the efficacy measures responses showed consistent, “modest” improvements in the patients who received a 2.5 mg injection followed by a 5 mg injection, compared with those who received two 2.5 mg injections.
For the safety analysis the researchers followed patients out to 24 weeks after they received their final injection. The main adverse event of interest was rapidly progressive OA (RPOA), which occurred in five patients who received two 2.5-mg dosages and in one patient who received the 2.5 mg followed by 5 mg regimen; no RPOA occurred among placebo patients. The 1.3% incidence of RPOA among all 494 patients who received tanezumab “aligned with expectations based on the risk mitigation procedures used,” said Dr. Schnitzer, a rheumatologist and professor of medicine, anesthesiology, and physical medicine and rehabilitation at Northwestern University, Chicago. No patient developed primary osteonecrosis.
Two patients who developed RPOA then underwent total joint replacement. The overall rate of total joint replacement was 4 among placebo patients, all involving knees, and 24 among patients treated with tanezumab, including 12 knee replacements and 12 hip replacements. Blinded adjudication determined that 26 of the total 28 joint replacements resulted from “normal” OA progression.
The rates of all adverse events, serious adverse events, and adverse events leading to treatment discontinuation were low and similar in the three treatment arms.
Earlier clinical studies of tanezumab had signaled a problem with RPOA (Arthritis Rheumatol. 2016 Feb;68[2]:382-91), which led the Food and Drug Administration to order a temporary halt to clinical testing of all nerve growth factor antagonists in 2010 that the agency then lifted in 2015 (Clin Exp Rheumatol. 2017 Sept-Oct;35[suppl 107]:85-7). In 2017, the FDA gave clinical development of tanezumab “fast-track” status. The results that Dr. Schnitzer reported represent the first outcomes from several phase 3 studies that the companies developing tanezumab are now running and that collectively include about 7,000 total patients, according to a written statement from the developing companies. The companies released an initial statement about the current results in July 2018.
The study reported by Dr. Schnitzer enrolled patients with OA of the knee or hip at several U.S. sites. For the primary endpoint of mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the results at 16 weeks were –2.6 units in the placebo patients and –3.4 units among patients who received the higher dosage. For the primary outcome of mean change in WOMAC physical function score, the results were –2.6 in the placebo arm and –3.5 in patients on the higher dosage. For the primary outcome of change in patient’s global assessment of their OA, the results were –0.65 in the placebo patients and –0.90 in those on the highest dosage. All three between-group differences were statistically significant.
A key secondary outcome was the percentage of patients having at least a 50% reduction in their WOMAC pain score, which occurred in 38% of the placebo patients and in 57% on the higher tanezumab dosage, a statistically significant difference, Dr. Schnitzer reported. A final efficacy finding was the percentage of patients who had a 50% or greater pain reduction at week 16 who did not have a pain response at week 8, a parameter that could reflect incremental benefit from the larger, second tanezumab dose. This outcome occurred in 19% of placebo patients and in 22% of patients who received two 2.5-mg doses of tanezumab; among those who received a 5-mg dose after the first 2.5-mg dose, the rate was 33%.
The study was sponsored by Eli Lilly and Pfizer, the companies jointly developing tanezumab. Dr. Schnitzer has been a consultant to and has received research support from Eli Lilly and Pfizer. He has also been a consultant to AbbVie, Aptinyx, Genzyme, Regeneron, and Vertex Pharmaceuticals, and has received research support from Grünenthal and Radius Health.
SOURCE: Schnitzer TJ et al. Arthritis Rheumatol. 2018;70(Suppl 10) Abstract L20.
CHICAGO – The nerve growth factor antibody tanezumab met its primary efficacy endpoints for improving pain and physical function in patients with knee or hip OA while also showing a low incidence of the drug’s most concerning adverse effect in the first results from a phase 3 study of a drug in this new class.
The placebo-controlled, multicenter study enrolled 696 U.S. OA patients with moderate to severe knee or hip pain and showed that two subcutaneous injections of the humanized antibody tanezumab spaced 8 weeks apart led to statistically significant improvements relative to placebo for pain, physical function, and patient global assessment of OA, Thomas J. Schnitzer, MD, said at the annual meeting of the American College of Rheumatology.
The primary efficacy measurements occurred 8 weeks following the second subcutaneous injection. The study included two active treatment arms, and all the efficacy measures responses showed consistent, “modest” improvements in the patients who received a 2.5 mg injection followed by a 5 mg injection, compared with those who received two 2.5 mg injections.
For the safety analysis the researchers followed patients out to 24 weeks after they received their final injection. The main adverse event of interest was rapidly progressive OA (RPOA), which occurred in five patients who received two 2.5-mg dosages and in one patient who received the 2.5 mg followed by 5 mg regimen; no RPOA occurred among placebo patients. The 1.3% incidence of RPOA among all 494 patients who received tanezumab “aligned with expectations based on the risk mitigation procedures used,” said Dr. Schnitzer, a rheumatologist and professor of medicine, anesthesiology, and physical medicine and rehabilitation at Northwestern University, Chicago. No patient developed primary osteonecrosis.
Two patients who developed RPOA then underwent total joint replacement. The overall rate of total joint replacement was 4 among placebo patients, all involving knees, and 24 among patients treated with tanezumab, including 12 knee replacements and 12 hip replacements. Blinded adjudication determined that 26 of the total 28 joint replacements resulted from “normal” OA progression.
The rates of all adverse events, serious adverse events, and adverse events leading to treatment discontinuation were low and similar in the three treatment arms.
Earlier clinical studies of tanezumab had signaled a problem with RPOA (Arthritis Rheumatol. 2016 Feb;68[2]:382-91), which led the Food and Drug Administration to order a temporary halt to clinical testing of all nerve growth factor antagonists in 2010 that the agency then lifted in 2015 (Clin Exp Rheumatol. 2017 Sept-Oct;35[suppl 107]:85-7). In 2017, the FDA gave clinical development of tanezumab “fast-track” status. The results that Dr. Schnitzer reported represent the first outcomes from several phase 3 studies that the companies developing tanezumab are now running and that collectively include about 7,000 total patients, according to a written statement from the developing companies. The companies released an initial statement about the current results in July 2018.
The study reported by Dr. Schnitzer enrolled patients with OA of the knee or hip at several U.S. sites. For the primary endpoint of mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the results at 16 weeks were –2.6 units in the placebo patients and –3.4 units among patients who received the higher dosage. For the primary outcome of mean change in WOMAC physical function score, the results were –2.6 in the placebo arm and –3.5 in patients on the higher dosage. For the primary outcome of change in patient’s global assessment of their OA, the results were –0.65 in the placebo patients and –0.90 in those on the highest dosage. All three between-group differences were statistically significant.
A key secondary outcome was the percentage of patients having at least a 50% reduction in their WOMAC pain score, which occurred in 38% of the placebo patients and in 57% on the higher tanezumab dosage, a statistically significant difference, Dr. Schnitzer reported. A final efficacy finding was the percentage of patients who had a 50% or greater pain reduction at week 16 who did not have a pain response at week 8, a parameter that could reflect incremental benefit from the larger, second tanezumab dose. This outcome occurred in 19% of placebo patients and in 22% of patients who received two 2.5-mg doses of tanezumab; among those who received a 5-mg dose after the first 2.5-mg dose, the rate was 33%.
The study was sponsored by Eli Lilly and Pfizer, the companies jointly developing tanezumab. Dr. Schnitzer has been a consultant to and has received research support from Eli Lilly and Pfizer. He has also been a consultant to AbbVie, Aptinyx, Genzyme, Regeneron, and Vertex Pharmaceuticals, and has received research support from Grünenthal and Radius Health.
SOURCE: Schnitzer TJ et al. Arthritis Rheumatol. 2018;70(Suppl 10) Abstract L20.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The Western Ontario and McMaster Universities Osteoarthritis Index pain score fell by an average –3.4 points with maximum tanezumab treatment and by –2.6 points with placebo.
Study details: A multicenter, randomized study with 696 patients with moderate to severe OA of the knee or hip and moderate to severe pain.
Disclosures: The study was sponsored by Eli Lilly and Pfizer, the companies jointly developing tanezumab. Dr. Schnitzer has been a consultant to and has received research support from Eli Lilly and Pfizer. He has also been a consultant to AbbVie, Aptinyx, Genzyme, Regeneron, and Vertex Pharmaceuticals, and has received research support from Grünenthal and Radius Health.
Source: Schnitzer TJ et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract L20.
Montreal Cognitive Assessment fares well for rapid, reliable screening in SLE
CHICAGO – The Montreal Cognitive Assessment Test provides persuasive advantages over the standard neuropsychological test battery often recommended in guidelines as a screening tool for cognitive impairment in patients with systemic lupus erythematosus, Nicolas Paez-Venegas, MD, asserted at the annual meeting of the American College of Rheumatology.
The MoCA, as it’s known, offers brevity, simplicity, and none of the considerable expense and inconvenience of bringing in a trained specialist to administer a neuropsychological battery. Moreover, in a comparative efficacy study, the MoCA outperformed two other brief screening tools for cognitive impairment – the Mini-Mental State Examination and the Cognitive Symptom Inventory – and showed excellent correspondence with the results of the formal neuropsychological battery, reported Dr. Paez-Venegas, a psychiatrist at the Jalisco Institute of Mental Health, in Zapopan, Mexico.
He presented a cross-sectional study that pitted the three brief screening tests against a gold-standard neuropsychological battery in 44 patients with systemic lupus erythematosus (SLE) according to the 2012 Systemic Lupus International Collaborating Clinics Criteria, none of whom had any known medical or psychiatric comorbidities.
The MoCA proved to have the best congruence with the findings of the neuropsychological battery, with an area under the curve of 99.4%, 84% sensitivity, and 100% specificity for cognitive impairment. The Mini-Mental State Examination had 55% sensitivity and 100% specificity, while the Cognitive Symptom Inventory displayed 55% sensitivity and 31% specificity.
“We therefore encourage rheumatologists to apply the MoCA test as a valuable and easily implemented tool for detecting cognitive impairment as part of an integrated approach in SLE,” Dr. Paez-Venegas said.
Periodic screening for cognitive impairment in patients with SLE is an important aspect of patient management because cognitive impairment is a common manifestation of the disease, affecting up to two-thirds of patients, and it can have a serious impact upon quality of life and self-concept. Because such screening isn’t a one-time event, resort to a neuropsychological battery becomes particularly problematic. The battery employed in this study included the Wechsler Adult Intelligence Scale–Fourth Edition test, the Digit-Symbol test, the Finger-Tapping test of motor control, the Stroop test, Trail Making A and B, the Paced Auditory Serial Addition test, letter-number sequencing, the Wechsler Vocabulary test, the Rey-Osterrieth complex figure test, semantic and phonemic fluency tests, and a test of verbal Spanish comprehension. The battery is a comprehensive tool often employed in research studies but is not well suited for use in a busy clinical practice.
Overall, 70% of the SLE patients demonstrated cognitive impairment in one or more domains on the neuropsychological battery. Processing speed was the most frequently affected domain, involving 23 of the 44 patients. Only a single patient displayed abnormal motor control.
The MoCA test assesses attention, executive function, concentration, language, memory, abstraction, orientation, visuospatial cognitive capacity, and calculation.
Dr. Paez-Venegas’s study was published online earlier this year (J Clin Rheumatol 2018 Jul 18. doi: 10.1097/RHU.0000000000000876). He reported having no financial conflicts regarding his study.
SOURCE: Paez-Venegas N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 708.
CHICAGO – The Montreal Cognitive Assessment Test provides persuasive advantages over the standard neuropsychological test battery often recommended in guidelines as a screening tool for cognitive impairment in patients with systemic lupus erythematosus, Nicolas Paez-Venegas, MD, asserted at the annual meeting of the American College of Rheumatology.
The MoCA, as it’s known, offers brevity, simplicity, and none of the considerable expense and inconvenience of bringing in a trained specialist to administer a neuropsychological battery. Moreover, in a comparative efficacy study, the MoCA outperformed two other brief screening tools for cognitive impairment – the Mini-Mental State Examination and the Cognitive Symptom Inventory – and showed excellent correspondence with the results of the formal neuropsychological battery, reported Dr. Paez-Venegas, a psychiatrist at the Jalisco Institute of Mental Health, in Zapopan, Mexico.
He presented a cross-sectional study that pitted the three brief screening tests against a gold-standard neuropsychological battery in 44 patients with systemic lupus erythematosus (SLE) according to the 2012 Systemic Lupus International Collaborating Clinics Criteria, none of whom had any known medical or psychiatric comorbidities.
The MoCA proved to have the best congruence with the findings of the neuropsychological battery, with an area under the curve of 99.4%, 84% sensitivity, and 100% specificity for cognitive impairment. The Mini-Mental State Examination had 55% sensitivity and 100% specificity, while the Cognitive Symptom Inventory displayed 55% sensitivity and 31% specificity.
“We therefore encourage rheumatologists to apply the MoCA test as a valuable and easily implemented tool for detecting cognitive impairment as part of an integrated approach in SLE,” Dr. Paez-Venegas said.
Periodic screening for cognitive impairment in patients with SLE is an important aspect of patient management because cognitive impairment is a common manifestation of the disease, affecting up to two-thirds of patients, and it can have a serious impact upon quality of life and self-concept. Because such screening isn’t a one-time event, resort to a neuropsychological battery becomes particularly problematic. The battery employed in this study included the Wechsler Adult Intelligence Scale–Fourth Edition test, the Digit-Symbol test, the Finger-Tapping test of motor control, the Stroop test, Trail Making A and B, the Paced Auditory Serial Addition test, letter-number sequencing, the Wechsler Vocabulary test, the Rey-Osterrieth complex figure test, semantic and phonemic fluency tests, and a test of verbal Spanish comprehension. The battery is a comprehensive tool often employed in research studies but is not well suited for use in a busy clinical practice.
Overall, 70% of the SLE patients demonstrated cognitive impairment in one or more domains on the neuropsychological battery. Processing speed was the most frequently affected domain, involving 23 of the 44 patients. Only a single patient displayed abnormal motor control.
The MoCA test assesses attention, executive function, concentration, language, memory, abstraction, orientation, visuospatial cognitive capacity, and calculation.
Dr. Paez-Venegas’s study was published online earlier this year (J Clin Rheumatol 2018 Jul 18. doi: 10.1097/RHU.0000000000000876). He reported having no financial conflicts regarding his study.
SOURCE: Paez-Venegas N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 708.
CHICAGO – The Montreal Cognitive Assessment Test provides persuasive advantages over the standard neuropsychological test battery often recommended in guidelines as a screening tool for cognitive impairment in patients with systemic lupus erythematosus, Nicolas Paez-Venegas, MD, asserted at the annual meeting of the American College of Rheumatology.
The MoCA, as it’s known, offers brevity, simplicity, and none of the considerable expense and inconvenience of bringing in a trained specialist to administer a neuropsychological battery. Moreover, in a comparative efficacy study, the MoCA outperformed two other brief screening tools for cognitive impairment – the Mini-Mental State Examination and the Cognitive Symptom Inventory – and showed excellent correspondence with the results of the formal neuropsychological battery, reported Dr. Paez-Venegas, a psychiatrist at the Jalisco Institute of Mental Health, in Zapopan, Mexico.
He presented a cross-sectional study that pitted the three brief screening tests against a gold-standard neuropsychological battery in 44 patients with systemic lupus erythematosus (SLE) according to the 2012 Systemic Lupus International Collaborating Clinics Criteria, none of whom had any known medical or psychiatric comorbidities.
The MoCA proved to have the best congruence with the findings of the neuropsychological battery, with an area under the curve of 99.4%, 84% sensitivity, and 100% specificity for cognitive impairment. The Mini-Mental State Examination had 55% sensitivity and 100% specificity, while the Cognitive Symptom Inventory displayed 55% sensitivity and 31% specificity.
“We therefore encourage rheumatologists to apply the MoCA test as a valuable and easily implemented tool for detecting cognitive impairment as part of an integrated approach in SLE,” Dr. Paez-Venegas said.
Periodic screening for cognitive impairment in patients with SLE is an important aspect of patient management because cognitive impairment is a common manifestation of the disease, affecting up to two-thirds of patients, and it can have a serious impact upon quality of life and self-concept. Because such screening isn’t a one-time event, resort to a neuropsychological battery becomes particularly problematic. The battery employed in this study included the Wechsler Adult Intelligence Scale–Fourth Edition test, the Digit-Symbol test, the Finger-Tapping test of motor control, the Stroop test, Trail Making A and B, the Paced Auditory Serial Addition test, letter-number sequencing, the Wechsler Vocabulary test, the Rey-Osterrieth complex figure test, semantic and phonemic fluency tests, and a test of verbal Spanish comprehension. The battery is a comprehensive tool often employed in research studies but is not well suited for use in a busy clinical practice.
Overall, 70% of the SLE patients demonstrated cognitive impairment in one or more domains on the neuropsychological battery. Processing speed was the most frequently affected domain, involving 23 of the 44 patients. Only a single patient displayed abnormal motor control.
The MoCA test assesses attention, executive function, concentration, language, memory, abstraction, orientation, visuospatial cognitive capacity, and calculation.
Dr. Paez-Venegas’s study was published online earlier this year (J Clin Rheumatol 2018 Jul 18. doi: 10.1097/RHU.0000000000000876). He reported having no financial conflicts regarding his study.
SOURCE: Paez-Venegas N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 708.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The Montreal Cognitive Assessment Test showed 84% sensitivity and 100% specificity for cognitive impairment in systemic lupus erythematosus patients.
Study details: This comparative effectiveness study included 44 systemic lupus erythematosus patients assessed for cognitive impairment using three different tools.
Disclosures: The presenter reported having no financial conflicts regarding this study, which was conducted free of commercial support.
Source: Paez-Venegas N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 708.
Gout: new data support treat-to-target approach
CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.
This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.
“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.
“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.
The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.
The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.
“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.
Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.
“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.
Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.
SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.
CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.
This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.
“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.
“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.
The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.
The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.
“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.
Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.
“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.
Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.
SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.
CHICAGO – Failure to reach the therapeutic target of a serum urate level below 6 mg/dL in gout patients is an independent risk factor for all-cause mortality conferring a 139% increased risk, Fernando Perez-Ruiz, MD, PhD, said at the annual meeting of the American College of Rheumatology.
This new finding from a prospective cohort study of 1,193 gout patients constitutes a ringing endorsement that a treat-to-target approach should become the standard in the management of this disease, declared Dr. Perez-Ruiz, a rheumatologist at Hospital Universitario Cruces, Barakaldo, Spain.
“This is encouraging news. We can say to patients and clinicians that we should make every effort to reach the therapeutic target. This is a concept that’s not new in medicine. We do it for diabetes, for hypertension, for hyperlipidemia, and I think now for the first time we will do it for gout,” the rheumatologist said at a press conference highlighting the study findings.
“A lot of physicians including, unfortunately, rheumatologists don’t treat gout to target. They feel like if a patient is doing nicely, that’s good enough. But it’s like lowering cholesterol: If you’re at 400 mg/dL and you go to 300, does that mean it’s fine and you won’t get a myocardial infarction?” he asked rhetorically.
The study included 1,193 gout patients with a mean age at baseline of 60 years, 6.8 years disease duration, and an average of 3-4 flares during the previous year. Mean follow-up was 48 months, translating to 4,830 patient-years of prospective observation. Overall mortality was 13%, mostly from cardiovascular causes.
The mean baseline serum urate level was 9.1 mg/dL. Although both ACR and EULAR guidelines recommend a serum urate level below 6 mg/dL as a therapeutic target, 16.3% of subjects had a level of 6 mg/dL or more despite treatment. The crude mortality rate during follow-up was 80.9 deaths per 1,000 person-years in those with serum urate levels of 6 mg/dL or more, compared with 25.7 per 1,000 person-years in patients with serum urate levels below 6 mg/dL. In a multivariate analysis adjusted for age, prior cardiovascular events, other comorbid conditions, sex, baseline serum urate level, alcohol intake, and other potential confounders, a serum urate of 6 mg/dL or more was independently associated with a 139% increased risk of mortality during follow-up.
“I think the message we would like to give to clinicians is, ‘If you can do that [i.e., maintain the serum urate level below 6 mg/dL], do it. You have the knowledge, you have the means, make the effort. Your patient will benefit from that. Don’t take risks,’” Dr. Perez-Ruiz said.
Session moderator Shraddha Jatwani, MD, a rheumatologist at St. Vincent Hospital in Evansville, Ind., pronounced this a message she will take home to her clinical practice.
“What we usually see in clinical practice is that gout patients are among the most noncompliant. Once they stop hurting they just don’t see the need to take their medication daily. And now that we have this data, we can tell them that their gout medications are like statins, which help reduce the risk of heart attacks. Taking their gout medication will help them reduce their mortality risk. This information will help us to change patient perception,” she said.
Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.
SOURCE: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Lowering serum urate in gout patients confers a survival advantage.
Major finding: A serum urate of 6 mg/dL or more in gout patients was independently associated with a 139% increased risk of all-cause mortality.
Study details: This was a prospective study of 1,193 gout patients followed for an average of 4 years.
Disclosures: Dr. Perez-Ruiz reported relationships with Amgen, Grünenthal, and Menarini.
Source: Perez-Ruiz F et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 869.
Tofacitinib and TNF inhibitors show similar VTE rates
CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.
The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.
Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.
In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.
Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.
The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.
The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.
Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.
CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.
The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.
Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.
In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.
Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.
The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.
The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.
Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.
CHICAGO – Rheumatoid arthritis patients treated with tofacitinib did not have a significantly increased incidence of hospitalization for venous thromboembolism, compared with patients treated with a tumor necrosis factor (TNF) inhibitor, in a study of more than 50,000 U.S. patients culled from a pair of health insurance databases.
The Janus kinase inhibitor class of agents, including tofacitinib (Xeljanz), has acquired a reputation for causing an excess of venous thromboembolic events (VTE) (Drug Saf. 2018 Jul;41[7]:645-53). To assess this in a real-world setting Seoyoung C. Kim, MD, and her associates took data from Medicare patients during 2012-2015 and from Truven MarketScan for commercially insured patients during 2012-2016 and derived a database of 16,091 RA patients on newly begun treatment with a TNF inhibitor and 995 newly begun on tofacitinib in the Medicare data, and 32,164 RA patients newly started on a TNF inhibitor and 1,910 on tofacitinib in the Truven database. The analysis excluded patients with a history of VTE.
Using propensity score–adjusted matching of patients in the two treatment arms in both of these databases, and using a VTE event – either a pulmonary embolism or deep-vein thrombosis that resulted in hospitalization – as the primary endpoint, the results showed statistically nonsignificant excesses of VTE in the patients treated with tofacitinib, compared with a TNF inhibitor, Dr. Kim reported in a poster she presented at the annual meeting of the American College of Rheumatology.
In the adjusted comparison, the Medicare data showed a nonsignificant 12% higher VTE rate in the tofacitinib-treated patients, while the Truven data showed a nonsignificant 55% higher rate of VTE during tofacitinib treatment. When the data were pooled, the result was a 33% higher rate of VTE while on tofacitinib treatment, which was not statistically significant.
Dr. Kim cautioned that the low rate of VTE events, especially among the patients on tofacitinib, limited the precision of the results. The combined data included 2,905 patients on tofacitinib treatment who had 15 VTE events, a rate of 0.77 events/100 person-years of follow-up. This compared with a rate of 0.52/100 person-years among patients on a TNF inhibitor. Thus, in both treatment groups the absolute VTE rate was low.
The most reliable finding from the analysis is that it “rules out a large increase in the risk for VTE events with tofacitinib,” said Dr. Kim, a rheumatologist at Brigham and Women’s Hospital in Boston.
The researchers also ran an analysis that included not only VTE events that resulted in hospitalization but also VTE events managed on an outpatient basis. Dr. Kim did not report the specific numbers involved in this calculation, but she reported that, when her group included both types of VTE events, the patients treated with tofacitinib had a nonsignificant 12% lower rate of events, compared with patients treated with a TNF inhibitor.
Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.
SOURCE: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Rheumatoid arthritis patients treated with tofacitinib showed no excess incidence of venous thromboembolism, compared with patients on a tumor necrosis factor inhibitor.
Major finding: Propensity score–adjusted rates of VTE were 33% higher with tofacitinib, compared with TNF inhibition, which was not a statistically significant difference.
Study details: Review of 51,160 rheumatoid arthritis patients from U.S. health insurance databases.
Disclosures: Dr. Kim has received research support from Bristol-Myers Squibb, Pfizer, and Roche.
Source: Desai RJ et al. Arthritis Rheumatol. 2018;70(suppl 10), Abstract L09.
Total knee replacement risk soars after arthroscopic surgery for meniscal tear
CHICAGO – A 5-year follow-up of a major randomized trial comparing methods of meniscal tear management in patients with osteoarthritis showed the risk of total knee replacement was 400% greater in patients who underwent arthroscopic partial meniscectomy than in those who received physical therapy alone, Jeffrey N. Katz, MD, reported at the annual meeting of the American College of Rheumatology.
At 5 years, however, the two divergent initial treatment strategies – arthroscopic surgical repair versus physical therapy – resulted in similar degrees of long-term pain improvement, noted Dr. Katz, a rheumatologist who is professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
“Because that’s the case, a reasonable recommendation – and one that most folks around the world who are thinking about this problem would make – is to have the first choice initially be nonoperative; that is, physical therapy, with surgery reserved for those who don’t improve and who have an interest in undertaking the risks of surgery,” he said.
Dr. Katz presented 5-year follow-up data on 341 participants in the MeTeOR trial, a seven-center study in which middle-age or older subjects with knee pain, a meniscal tear, and osteoarthritic changes on x-ray were randomized to arthroscopic repair or physical therapy. A lot rides on the outcomes of this study, as there is a longstanding debate over the balance of risks and benefits of arthroscopic surgery in this common clinical scenario.
Of the 351 participants, 164 were randomized to and received arthroscopic partial meniscectomy, 109 were randomized to and received a standardized program of physical therapy, and 68 were initially randomized to physical therapy but crossed over to arthroscopic surgery within the first few months because of lack of improvement.
At 5 years of follow-up, all three groups showed similar degrees of improvement in Knee Osteoarthritis and Injury Outcome Score Pain Scale scores, from 40-50 out of a possible 100 at baseline to 20-25 at 6 months, with little change thereafter through 5 years.
The eye-catching finding was the difference in the incidence of total knee replacement (TKR) through 5 years: 10% in those who underwent arthroscopic partial meniscectomy, either as initial therapy or after crossing over from the physical therapy group, compared with 2% in patients who underwent physical therapy alone. Given that more than 400,000 arthroscopic partial meniscectomies are done annually in the United States in patients with knee osteoarthritis, extrapolation from the MeTeOR results suggests an excess of 40,000 total knee replacements in surgically treated patients.
“The higher TKR rates that we observed in surgically treated patients are unexplained, concerning, and require further study. The finding is consistent with the observation in the Osteoarthritis Initiative that TKR rates were higher in patients with arthroscopy as opposed to those treated nonsurgically,” the rheumatologist said.
He proposed two possible explanations for the finding. “It does appear that people who have arthroscopic surgery are then, over the next 5 years, more likely to have total knee replacement. We don’t know whether that is because performing arthroscopic surgery is actually damaging the knee further, leading it to deteriorate more quickly and therefore go on to total knee replacement, or whether when patients develop a relationship with a surgeon and have arthroscopic surgery, they get over some of their apprehension about surgery and may become more likely to accept subsequent surgery for total knee replacement. We hope to find the answer. I think this story is still unfolding because 5 years is a relatively brief period of time in the course of osteoarthritis.
“Arthroscopic surgery certainly offers greater shorter-term improvement, and for some patients that’s worth trading off some downstream risk of joint damage, and for others, they would not want to make that trade-off. So I see it ultimately as a matter of patient choice,” Dr. Katz said.
Knee osteoarthritis affects an estimated 15 million Americans. More than one-half of them have a meniscal tear, the majority of which don’t cause symptoms.
Dr. Katz reported having no financial conflicts regarding MeTeOR, which was funded by the National Institutes of Health.
SOURCE: Katz JN et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1816.
CHICAGO – A 5-year follow-up of a major randomized trial comparing methods of meniscal tear management in patients with osteoarthritis showed the risk of total knee replacement was 400% greater in patients who underwent arthroscopic partial meniscectomy than in those who received physical therapy alone, Jeffrey N. Katz, MD, reported at the annual meeting of the American College of Rheumatology.
At 5 years, however, the two divergent initial treatment strategies – arthroscopic surgical repair versus physical therapy – resulted in similar degrees of long-term pain improvement, noted Dr. Katz, a rheumatologist who is professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
“Because that’s the case, a reasonable recommendation – and one that most folks around the world who are thinking about this problem would make – is to have the first choice initially be nonoperative; that is, physical therapy, with surgery reserved for those who don’t improve and who have an interest in undertaking the risks of surgery,” he said.
Dr. Katz presented 5-year follow-up data on 341 participants in the MeTeOR trial, a seven-center study in which middle-age or older subjects with knee pain, a meniscal tear, and osteoarthritic changes on x-ray were randomized to arthroscopic repair or physical therapy. A lot rides on the outcomes of this study, as there is a longstanding debate over the balance of risks and benefits of arthroscopic surgery in this common clinical scenario.
Of the 351 participants, 164 were randomized to and received arthroscopic partial meniscectomy, 109 were randomized to and received a standardized program of physical therapy, and 68 were initially randomized to physical therapy but crossed over to arthroscopic surgery within the first few months because of lack of improvement.
At 5 years of follow-up, all three groups showed similar degrees of improvement in Knee Osteoarthritis and Injury Outcome Score Pain Scale scores, from 40-50 out of a possible 100 at baseline to 20-25 at 6 months, with little change thereafter through 5 years.
The eye-catching finding was the difference in the incidence of total knee replacement (TKR) through 5 years: 10% in those who underwent arthroscopic partial meniscectomy, either as initial therapy or after crossing over from the physical therapy group, compared with 2% in patients who underwent physical therapy alone. Given that more than 400,000 arthroscopic partial meniscectomies are done annually in the United States in patients with knee osteoarthritis, extrapolation from the MeTeOR results suggests an excess of 40,000 total knee replacements in surgically treated patients.
“The higher TKR rates that we observed in surgically treated patients are unexplained, concerning, and require further study. The finding is consistent with the observation in the Osteoarthritis Initiative that TKR rates were higher in patients with arthroscopy as opposed to those treated nonsurgically,” the rheumatologist said.
He proposed two possible explanations for the finding. “It does appear that people who have arthroscopic surgery are then, over the next 5 years, more likely to have total knee replacement. We don’t know whether that is because performing arthroscopic surgery is actually damaging the knee further, leading it to deteriorate more quickly and therefore go on to total knee replacement, or whether when patients develop a relationship with a surgeon and have arthroscopic surgery, they get over some of their apprehension about surgery and may become more likely to accept subsequent surgery for total knee replacement. We hope to find the answer. I think this story is still unfolding because 5 years is a relatively brief period of time in the course of osteoarthritis.
“Arthroscopic surgery certainly offers greater shorter-term improvement, and for some patients that’s worth trading off some downstream risk of joint damage, and for others, they would not want to make that trade-off. So I see it ultimately as a matter of patient choice,” Dr. Katz said.
Knee osteoarthritis affects an estimated 15 million Americans. More than one-half of them have a meniscal tear, the majority of which don’t cause symptoms.
Dr. Katz reported having no financial conflicts regarding MeTeOR, which was funded by the National Institutes of Health.
SOURCE: Katz JN et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1816.
CHICAGO – A 5-year follow-up of a major randomized trial comparing methods of meniscal tear management in patients with osteoarthritis showed the risk of total knee replacement was 400% greater in patients who underwent arthroscopic partial meniscectomy than in those who received physical therapy alone, Jeffrey N. Katz, MD, reported at the annual meeting of the American College of Rheumatology.
At 5 years, however, the two divergent initial treatment strategies – arthroscopic surgical repair versus physical therapy – resulted in similar degrees of long-term pain improvement, noted Dr. Katz, a rheumatologist who is professor of medicine and orthopedic surgery at Harvard Medical School, Boston.
“Because that’s the case, a reasonable recommendation – and one that most folks around the world who are thinking about this problem would make – is to have the first choice initially be nonoperative; that is, physical therapy, with surgery reserved for those who don’t improve and who have an interest in undertaking the risks of surgery,” he said.
Dr. Katz presented 5-year follow-up data on 341 participants in the MeTeOR trial, a seven-center study in which middle-age or older subjects with knee pain, a meniscal tear, and osteoarthritic changes on x-ray were randomized to arthroscopic repair or physical therapy. A lot rides on the outcomes of this study, as there is a longstanding debate over the balance of risks and benefits of arthroscopic surgery in this common clinical scenario.
Of the 351 participants, 164 were randomized to and received arthroscopic partial meniscectomy, 109 were randomized to and received a standardized program of physical therapy, and 68 were initially randomized to physical therapy but crossed over to arthroscopic surgery within the first few months because of lack of improvement.
At 5 years of follow-up, all three groups showed similar degrees of improvement in Knee Osteoarthritis and Injury Outcome Score Pain Scale scores, from 40-50 out of a possible 100 at baseline to 20-25 at 6 months, with little change thereafter through 5 years.
The eye-catching finding was the difference in the incidence of total knee replacement (TKR) through 5 years: 10% in those who underwent arthroscopic partial meniscectomy, either as initial therapy or after crossing over from the physical therapy group, compared with 2% in patients who underwent physical therapy alone. Given that more than 400,000 arthroscopic partial meniscectomies are done annually in the United States in patients with knee osteoarthritis, extrapolation from the MeTeOR results suggests an excess of 40,000 total knee replacements in surgically treated patients.
“The higher TKR rates that we observed in surgically treated patients are unexplained, concerning, and require further study. The finding is consistent with the observation in the Osteoarthritis Initiative that TKR rates were higher in patients with arthroscopy as opposed to those treated nonsurgically,” the rheumatologist said.
He proposed two possible explanations for the finding. “It does appear that people who have arthroscopic surgery are then, over the next 5 years, more likely to have total knee replacement. We don’t know whether that is because performing arthroscopic surgery is actually damaging the knee further, leading it to deteriorate more quickly and therefore go on to total knee replacement, or whether when patients develop a relationship with a surgeon and have arthroscopic surgery, they get over some of their apprehension about surgery and may become more likely to accept subsequent surgery for total knee replacement. We hope to find the answer. I think this story is still unfolding because 5 years is a relatively brief period of time in the course of osteoarthritis.
“Arthroscopic surgery certainly offers greater shorter-term improvement, and for some patients that’s worth trading off some downstream risk of joint damage, and for others, they would not want to make that trade-off. So I see it ultimately as a matter of patient choice,” Dr. Katz said.
Knee osteoarthritis affects an estimated 15 million Americans. More than one-half of them have a meniscal tear, the majority of which don’t cause symptoms.
Dr. Katz reported having no financial conflicts regarding MeTeOR, which was funded by the National Institutes of Health.
SOURCE: Katz JN et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1816.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Risk of total knee replacement is five times higher after arthroscopic partial meniscectomy.
Major finding: Patients randomized to arthroscopic partial meniscectomy were 400% more likely to subsequently undergo total knee replacement than were those randomized to physical therapy alone.
Study details: This was a presentation of the 5-year follow-up results in 341 participants in the MeTeOR trial, a seven-center study in which middle-age or older subjects with knee pain, a meniscal tear, and osteoarthritic changes on x-ray were randomized to arthroscopic repair or physical therapy.
Disclosures: The presenter reported having no financial conflicts regarding MeTeOR, which was funded by the National Institutes of Health.
Source: Katz JN et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1816.
High incidence of treatment-resistant hypertension in SLE comes with high mortality
CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.
TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.
She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.
TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.
The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m2), and a higher creatinine (1.1 versus 0.8 mg/day).
Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.
Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.
SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.
CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.
TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.
She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.
TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.
The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m2), and a higher creatinine (1.1 versus 0.8 mg/day).
Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.
Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.
SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.
CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.
TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.
She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.
TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.
The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m2), and a higher creatinine (1.1 versus 0.8 mg/day).
Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.
Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.
SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: Treatment-resistant hypertension is an important yet underappreciated comorbidity for clinicians to recognize in patients with systemic lupus erythematosus.
Major finding: The incidence rate of treatment-resistant hypertension was twice as great in patients with systemic lupus erythematosus compared with matched controls.
Study details: This retrospective, single-center study included 1,044 systemic lupus erythematosus patients and 5,241 matched controls.
Disclosures: The presenter reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.
Source: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.
Development of reversible B-cell inhibitor XmAb5871 for SLE moves forward
CHICAGO – The novel reversible B-cell inhibitor XmAb5871 showed promise for delaying loss of improvement after steroid therapy in patients with systemic lupus erythematosus in a randomized, placebo-controlled, phase 2 study.
Patients with moderate to severe nonorgan-threatening systemic lupus erythematosus (SLE) who underwent biweekly treatment with XmAb5871 after intramuscular glucocorticoid therapy more often achieved the trial’s primary endpoint of no loss of improvement through day 225 than did patients who took placebo. Overall, 21 (42%) of 50 patients who were randomized to receive active treatment reached this outcome, compared with 12 (29%) of 42 who received placebo based on the “efficacy-evaluable” patient population, defined as those who completed day 225, had a loss of improvement, or discontinued because of a drug-related adverse even. The difference between the treatment and placebo groups with respect to loss of improvement through day 225 reflected a positive trend, but did not reach statistical significance (P = .18), Debra J. Zack, MD, of Xencor in Monrovia, Calif., and her colleagues reported in a poster at the annual meeting of the American College of Rheumatology.
Of the patients who didn’t achieve the primary endpoint, 23 (46%) in the XmAb5871 arm versus 30 (71%) in the placebo arm experienced loss of improvement at any visit, the investigators noted. Six patients in the treatment arm discontinued for toxicity and were also considered nonresponders.
Treatment with XmAb5871 also led to a longer median time to loss of improvement of 230 days in comparison with the 130 days observed in placebo-treated patients. The difference was statistically significant in the efficacy-evaluable population (hazard ratio, 0.53; P = .025) and nearly statistically significant in the intent-to-treat (ITT) population of 52 patients in each group (HR, 0.59; P = .06), they noted.
Maintenance of improvement, which was another secondary endpoint, did not differ significantly between the groups in the efficacy-evaluable population (58.0% vs. 40.5%, respectively; P = .11), but did differ significantly with treatment versus placebo at both day 225 (response rates of 44.0% vs. 23.1%, respectively; P = .06) and at day 169 (57.7% vs. 34.6%; P = .02) in the ITT population, they said.
Of note, patients in the treatment group stayed in the study longer (median of 6.9 vs. 3.6 months) and received more infusions (median of 15.0 vs. 8.5).
“Antigen-activated B cells are down-regulated by engagement of immune complexes with the inhibitory Fcy receptor FcyRIIB on the B cell surface. XmAb5871 is an anti-CD19 monoclonal antibody engineered to enhance binding to FcyRIIB,” they explained, adding that the study was designed using unique methodology to minimize background medication and placebo responses to allow for better interpretation of the results in patients with complex, heterogeneous disease.
Participants were adults with a median age of 44.5 years; most (99 of 104) were women. All received an intramuscular glucocorticoid injection at the start of the screening period as background immunosuppressants were stopped, and those who experienced at least a 4-point decrease on the SLE disease activity index or at least a 1-grade decrease in at least one British Isles Lupus Activity Group A or B score were eligible for enrollment. Background immunosuppressants had to be stopped by the time of enrollment, but patients were allowed to remain on hydroxychloroquine and prednisone 10 mg or less daily or the equivalent.
Those enrolled were randomized to receive intravenous XmAb5871 at a dose of 5 mg/kg or placebo every 14 days for up to 16 doses until day 225 or loss of improvement (at which time patients could receive standard of care and withdraw from the study); all received intramuscular glucocorticoids (Depo-Medrol 80 mg [methylprednisolone acetate]) on days 1 and 15.
XmAb5871 was well tolerated in this study and had a safety profile consistent with that seen in previous SLE studies, with the exception of six withdrawals caused by infusion reactions, the investigators said. They noted that a subcutaneous formulation showed no infusion reactions or gastrointestinal-related infusion reactions in a bioavailability study of 40 healthy subjects, and so a formulation for subcutaneous injection will be used in future studies.
The vast majority of the 149 treatment-related adverse events that occurred in 41 patients in the current study (including 26% in placebo group patients) were mild or moderate in severity. A total of 13 serious adverse events (SAEs) occurred in 11 patients, and included fever, SLE flare (lung), atrial fibrillation, worsening hypertension, iron deficiency anemia, pneumonia (occurring 36 days, or 10 half-lives, after the last dose), infusion-related reaction, and vertigo in the XmAb5871 patients, and anemia SLE flare, SLE flare (enteritis), angioedema, and migraine headache in the placebo group.
“All SAEs were considered not or unlikely related except the infusion-related reaction. There were no deaths and no opportunistic infections,” they wrote.
Although the primary endpoint of loss of improvement by day 225 was not significantly better in the treatment group in this study, a positive trend was noted, the median time to loss of improvement was extended by 76%, and the risk of increased SLE disease activity was reduced by 47% in those who received XmAb5871, they said, concluding that the findings support further evaluation of the agent in patients with SLE.
The study was supported by Xencor.
SOURCE: Zack DJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L14.
CHICAGO – The novel reversible B-cell inhibitor XmAb5871 showed promise for delaying loss of improvement after steroid therapy in patients with systemic lupus erythematosus in a randomized, placebo-controlled, phase 2 study.
Patients with moderate to severe nonorgan-threatening systemic lupus erythematosus (SLE) who underwent biweekly treatment with XmAb5871 after intramuscular glucocorticoid therapy more often achieved the trial’s primary endpoint of no loss of improvement through day 225 than did patients who took placebo. Overall, 21 (42%) of 50 patients who were randomized to receive active treatment reached this outcome, compared with 12 (29%) of 42 who received placebo based on the “efficacy-evaluable” patient population, defined as those who completed day 225, had a loss of improvement, or discontinued because of a drug-related adverse even. The difference between the treatment and placebo groups with respect to loss of improvement through day 225 reflected a positive trend, but did not reach statistical significance (P = .18), Debra J. Zack, MD, of Xencor in Monrovia, Calif., and her colleagues reported in a poster at the annual meeting of the American College of Rheumatology.
Of the patients who didn’t achieve the primary endpoint, 23 (46%) in the XmAb5871 arm versus 30 (71%) in the placebo arm experienced loss of improvement at any visit, the investigators noted. Six patients in the treatment arm discontinued for toxicity and were also considered nonresponders.
Treatment with XmAb5871 also led to a longer median time to loss of improvement of 230 days in comparison with the 130 days observed in placebo-treated patients. The difference was statistically significant in the efficacy-evaluable population (hazard ratio, 0.53; P = .025) and nearly statistically significant in the intent-to-treat (ITT) population of 52 patients in each group (HR, 0.59; P = .06), they noted.
Maintenance of improvement, which was another secondary endpoint, did not differ significantly between the groups in the efficacy-evaluable population (58.0% vs. 40.5%, respectively; P = .11), but did differ significantly with treatment versus placebo at both day 225 (response rates of 44.0% vs. 23.1%, respectively; P = .06) and at day 169 (57.7% vs. 34.6%; P = .02) in the ITT population, they said.
Of note, patients in the treatment group stayed in the study longer (median of 6.9 vs. 3.6 months) and received more infusions (median of 15.0 vs. 8.5).
“Antigen-activated B cells are down-regulated by engagement of immune complexes with the inhibitory Fcy receptor FcyRIIB on the B cell surface. XmAb5871 is an anti-CD19 monoclonal antibody engineered to enhance binding to FcyRIIB,” they explained, adding that the study was designed using unique methodology to minimize background medication and placebo responses to allow for better interpretation of the results in patients with complex, heterogeneous disease.
Participants were adults with a median age of 44.5 years; most (99 of 104) were women. All received an intramuscular glucocorticoid injection at the start of the screening period as background immunosuppressants were stopped, and those who experienced at least a 4-point decrease on the SLE disease activity index or at least a 1-grade decrease in at least one British Isles Lupus Activity Group A or B score were eligible for enrollment. Background immunosuppressants had to be stopped by the time of enrollment, but patients were allowed to remain on hydroxychloroquine and prednisone 10 mg or less daily or the equivalent.
Those enrolled were randomized to receive intravenous XmAb5871 at a dose of 5 mg/kg or placebo every 14 days for up to 16 doses until day 225 or loss of improvement (at which time patients could receive standard of care and withdraw from the study); all received intramuscular glucocorticoids (Depo-Medrol 80 mg [methylprednisolone acetate]) on days 1 and 15.
XmAb5871 was well tolerated in this study and had a safety profile consistent with that seen in previous SLE studies, with the exception of six withdrawals caused by infusion reactions, the investigators said. They noted that a subcutaneous formulation showed no infusion reactions or gastrointestinal-related infusion reactions in a bioavailability study of 40 healthy subjects, and so a formulation for subcutaneous injection will be used in future studies.
The vast majority of the 149 treatment-related adverse events that occurred in 41 patients in the current study (including 26% in placebo group patients) were mild or moderate in severity. A total of 13 serious adverse events (SAEs) occurred in 11 patients, and included fever, SLE flare (lung), atrial fibrillation, worsening hypertension, iron deficiency anemia, pneumonia (occurring 36 days, or 10 half-lives, after the last dose), infusion-related reaction, and vertigo in the XmAb5871 patients, and anemia SLE flare, SLE flare (enteritis), angioedema, and migraine headache in the placebo group.
“All SAEs were considered not or unlikely related except the infusion-related reaction. There were no deaths and no opportunistic infections,” they wrote.
Although the primary endpoint of loss of improvement by day 225 was not significantly better in the treatment group in this study, a positive trend was noted, the median time to loss of improvement was extended by 76%, and the risk of increased SLE disease activity was reduced by 47% in those who received XmAb5871, they said, concluding that the findings support further evaluation of the agent in patients with SLE.
The study was supported by Xencor.
SOURCE: Zack DJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L14.
CHICAGO – The novel reversible B-cell inhibitor XmAb5871 showed promise for delaying loss of improvement after steroid therapy in patients with systemic lupus erythematosus in a randomized, placebo-controlled, phase 2 study.
Patients with moderate to severe nonorgan-threatening systemic lupus erythematosus (SLE) who underwent biweekly treatment with XmAb5871 after intramuscular glucocorticoid therapy more often achieved the trial’s primary endpoint of no loss of improvement through day 225 than did patients who took placebo. Overall, 21 (42%) of 50 patients who were randomized to receive active treatment reached this outcome, compared with 12 (29%) of 42 who received placebo based on the “efficacy-evaluable” patient population, defined as those who completed day 225, had a loss of improvement, or discontinued because of a drug-related adverse even. The difference between the treatment and placebo groups with respect to loss of improvement through day 225 reflected a positive trend, but did not reach statistical significance (P = .18), Debra J. Zack, MD, of Xencor in Monrovia, Calif., and her colleagues reported in a poster at the annual meeting of the American College of Rheumatology.
Of the patients who didn’t achieve the primary endpoint, 23 (46%) in the XmAb5871 arm versus 30 (71%) in the placebo arm experienced loss of improvement at any visit, the investigators noted. Six patients in the treatment arm discontinued for toxicity and were also considered nonresponders.
Treatment with XmAb5871 also led to a longer median time to loss of improvement of 230 days in comparison with the 130 days observed in placebo-treated patients. The difference was statistically significant in the efficacy-evaluable population (hazard ratio, 0.53; P = .025) and nearly statistically significant in the intent-to-treat (ITT) population of 52 patients in each group (HR, 0.59; P = .06), they noted.
Maintenance of improvement, which was another secondary endpoint, did not differ significantly between the groups in the efficacy-evaluable population (58.0% vs. 40.5%, respectively; P = .11), but did differ significantly with treatment versus placebo at both day 225 (response rates of 44.0% vs. 23.1%, respectively; P = .06) and at day 169 (57.7% vs. 34.6%; P = .02) in the ITT population, they said.
Of note, patients in the treatment group stayed in the study longer (median of 6.9 vs. 3.6 months) and received more infusions (median of 15.0 vs. 8.5).
“Antigen-activated B cells are down-regulated by engagement of immune complexes with the inhibitory Fcy receptor FcyRIIB on the B cell surface. XmAb5871 is an anti-CD19 monoclonal antibody engineered to enhance binding to FcyRIIB,” they explained, adding that the study was designed using unique methodology to minimize background medication and placebo responses to allow for better interpretation of the results in patients with complex, heterogeneous disease.
Participants were adults with a median age of 44.5 years; most (99 of 104) were women. All received an intramuscular glucocorticoid injection at the start of the screening period as background immunosuppressants were stopped, and those who experienced at least a 4-point decrease on the SLE disease activity index or at least a 1-grade decrease in at least one British Isles Lupus Activity Group A or B score were eligible for enrollment. Background immunosuppressants had to be stopped by the time of enrollment, but patients were allowed to remain on hydroxychloroquine and prednisone 10 mg or less daily or the equivalent.
Those enrolled were randomized to receive intravenous XmAb5871 at a dose of 5 mg/kg or placebo every 14 days for up to 16 doses until day 225 or loss of improvement (at which time patients could receive standard of care and withdraw from the study); all received intramuscular glucocorticoids (Depo-Medrol 80 mg [methylprednisolone acetate]) on days 1 and 15.
XmAb5871 was well tolerated in this study and had a safety profile consistent with that seen in previous SLE studies, with the exception of six withdrawals caused by infusion reactions, the investigators said. They noted that a subcutaneous formulation showed no infusion reactions or gastrointestinal-related infusion reactions in a bioavailability study of 40 healthy subjects, and so a formulation for subcutaneous injection will be used in future studies.
The vast majority of the 149 treatment-related adverse events that occurred in 41 patients in the current study (including 26% in placebo group patients) were mild or moderate in severity. A total of 13 serious adverse events (SAEs) occurred in 11 patients, and included fever, SLE flare (lung), atrial fibrillation, worsening hypertension, iron deficiency anemia, pneumonia (occurring 36 days, or 10 half-lives, after the last dose), infusion-related reaction, and vertigo in the XmAb5871 patients, and anemia SLE flare, SLE flare (enteritis), angioedema, and migraine headache in the placebo group.
“All SAEs were considered not or unlikely related except the infusion-related reaction. There were no deaths and no opportunistic infections,” they wrote.
Although the primary endpoint of loss of improvement by day 225 was not significantly better in the treatment group in this study, a positive trend was noted, the median time to loss of improvement was extended by 76%, and the risk of increased SLE disease activity was reduced by 47% in those who received XmAb5871, they said, concluding that the findings support further evaluation of the agent in patients with SLE.
The study was supported by Xencor.
SOURCE: Zack DJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L14.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point: XmAb5871 shows promise in systemic lupus erythematosus.
Major finding: There was no loss of improvement through day 225 in 42% of patients treated with XmAb5871 versus 29% with placebo.
Study details: A randomized, placebo-controlled, phase 2 study.
Disclosures: The study was supported by Xencor. Dr. Zack is an employee of Xencor.
Source: Zack DJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L14.
Fear of blindness hobbles hydroxychloroquine treatment of SLE
CHICAGO – The dosage of hydroxychloroquine (HCQ) for treating patients with systemic lupus erythematosus (SLE) is often overly influenced by fear that the drug could cause blindness, Michelle A. Petri, MD, said at the annual meeting of the American College of Rheumatology.
HCQ “is the most important drug we have to treat lupus. It’s the only treatment shown to improve survival of lupus patients. There is no reason to make patients afraid of this very important drug. I am very concerned that fear of blindness is causing our patients to be less adherent” or making them receive an inadequate dosage, said Dr. Petri, a professor of medicine and the director of the Lupus Center at Johns Hopkins University in Baltimore. “I have had no patients who went blind on HCQ. A few patients developed retinopathy, but none went blind.”
Dr. Petri spoke about experiences with some of her SLE patients who were frightened by what an ophthalmologist told them about the retinal effects of HCQ and had their dosage of the drug unilaterally cut by the ophthalmologist.
“The message we should give patients is that retinopathy is a real complication that can happen, but usually not until after 16 years of treatment with HCQ, and we will work together to make sure you are regularly screened so that, if retinopathy developed, we would pick it up early and you’ll remain asymptomatic,” she said. ”We need to put the risk into perspective for our patients.”
Reports differ on the incidence of retinopathy in SLE patients on long-term HCQ treatment. During the session in which Dr. Petri spoke, James T. Rosenbaum, MD, cited a seminal report from 2014 that tracked 2,361 U.S. patients treated with HCQ daily for at least 5 years with regular retinal follow-up. The results showed a steady, cumulative increase in patients who developed retinopathy, an increase that was also dose dependent. For example, patients who received daily dosage of 5-5.9 mg/kg and took the drug for 20 or more years had a cumulative retinopathy incidence of 30% (JAMA Opthalmol. 2014 Dec;132[12]:1453-60). For patients on higher dosages, the cumulative risk at 20 years or longer jumped above 50%.
The findings from this study led directly to the most recent recommendations from the American Academy of Ophthalmology for retinopathy screening for patients on chronic HCQ treatment, said Dr. Rosenbaum, a professor of medicine and opthalmology at Oregon Health & Science University in Portland. The recommendations called for a dosage cap of less than 5 mg/kg real weight, a baseline retinal examination, and then at least annual follow-up examinations starting after 5 years of daily HCQ use, ideally using both automated visual fields and spectral-domain optical coherence tomography (Ophthalmology. 2016 June;123[6]:1386-94). The recommendations also noted that the presence of retinopathy risk factors, including renal disease or concomitant tamoxifen use, warrant starting screening at 5 years or sooner on HCQ.
Clinicians have often exceeded recommended dosage guidelines. Dr. Rosenbaum cited a 2017 report from one U.S. health care system that reviewed the treatment of 554 patients on HCQ and found that roughly half were overdosed in their starting regimen based on prevailing treatment recommendations (Opthalmology. 2017 May;124[5]:604-8).
But Dr. Petri contended that concerns about excessive HCQ dosages are overblown. At the meeting, she reported data showing a different perspective on the retinopathy risk of patients on chronic HCQ treatment. In a prospective series of 477 SLE patients on chronic HCQ treatment and followed at Johns Hopkins, the incidence of retinopathy was 10% among patients on treatment for 16 or more years, she reported in a talk at the meeting (Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2897).
A 10% retinopathy rate after 16 or more years on treatment “sounds a lot safer to patients” than rates as high as 30% or 50% that were reported in the JAMA Opthalmology report from 2014, Dr. Petri said. “There is a danger relying on one retrospective study,” she warned. In addition, the 10% risk for retinopathy is “manageable” when patients receive regular screening that produces early detection of retinal damage.
“There has been acceptance of suboptimal dosing of HCQ when discussion has only been about safety, not about efficacy. We need to put the risks into perspective and stop scaring patients.”
Dr. Petri presented her recommendations for treating SLE patients with HCQ: Treat with dosages as high as 6.5 mg/kg but without exceeding 400 mg/day, and cut the dosage for patients with renal insufficiency or failure, those with liver disease, or the elderly. In addition, Dr. Petri endorsed monitoring blood levels of HCQ. Data she reported at the meeting showed a roughly fourfold higher rate of retinopathy among patients who had a maximum HCQ blood level of 1,733 ng/mL or higher when compared with patients whose maximum level remained at 1,194 ng/mL or lower. Clinicians could use blood levels of HCQ to better focus screening and its intensity, she said. “We should embrace monitoring HCQ blood levels.”
Dr. Petri has been a consultant to Amgen, Exagen, GlaxoSmithKline, Inova Diagnostics, Janssen, Lilly, Merck, Novartis, Quintiles, and EMD Serono, and she has received research funding from AstraZeneca and Exagen. Dr. Rosenbaum has been a consultant to AbbVie, Eyevensys, Gilead, Janssen, Novartis, Regeneron, and Roche, and has received research funding from Pfizer.
CHICAGO – The dosage of hydroxychloroquine (HCQ) for treating patients with systemic lupus erythematosus (SLE) is often overly influenced by fear that the drug could cause blindness, Michelle A. Petri, MD, said at the annual meeting of the American College of Rheumatology.
HCQ “is the most important drug we have to treat lupus. It’s the only treatment shown to improve survival of lupus patients. There is no reason to make patients afraid of this very important drug. I am very concerned that fear of blindness is causing our patients to be less adherent” or making them receive an inadequate dosage, said Dr. Petri, a professor of medicine and the director of the Lupus Center at Johns Hopkins University in Baltimore. “I have had no patients who went blind on HCQ. A few patients developed retinopathy, but none went blind.”
Dr. Petri spoke about experiences with some of her SLE patients who were frightened by what an ophthalmologist told them about the retinal effects of HCQ and had their dosage of the drug unilaterally cut by the ophthalmologist.
“The message we should give patients is that retinopathy is a real complication that can happen, but usually not until after 16 years of treatment with HCQ, and we will work together to make sure you are regularly screened so that, if retinopathy developed, we would pick it up early and you’ll remain asymptomatic,” she said. ”We need to put the risk into perspective for our patients.”
Reports differ on the incidence of retinopathy in SLE patients on long-term HCQ treatment. During the session in which Dr. Petri spoke, James T. Rosenbaum, MD, cited a seminal report from 2014 that tracked 2,361 U.S. patients treated with HCQ daily for at least 5 years with regular retinal follow-up. The results showed a steady, cumulative increase in patients who developed retinopathy, an increase that was also dose dependent. For example, patients who received daily dosage of 5-5.9 mg/kg and took the drug for 20 or more years had a cumulative retinopathy incidence of 30% (JAMA Opthalmol. 2014 Dec;132[12]:1453-60). For patients on higher dosages, the cumulative risk at 20 years or longer jumped above 50%.
The findings from this study led directly to the most recent recommendations from the American Academy of Ophthalmology for retinopathy screening for patients on chronic HCQ treatment, said Dr. Rosenbaum, a professor of medicine and opthalmology at Oregon Health & Science University in Portland. The recommendations called for a dosage cap of less than 5 mg/kg real weight, a baseline retinal examination, and then at least annual follow-up examinations starting after 5 years of daily HCQ use, ideally using both automated visual fields and spectral-domain optical coherence tomography (Ophthalmology. 2016 June;123[6]:1386-94). The recommendations also noted that the presence of retinopathy risk factors, including renal disease or concomitant tamoxifen use, warrant starting screening at 5 years or sooner on HCQ.
Clinicians have often exceeded recommended dosage guidelines. Dr. Rosenbaum cited a 2017 report from one U.S. health care system that reviewed the treatment of 554 patients on HCQ and found that roughly half were overdosed in their starting regimen based on prevailing treatment recommendations (Opthalmology. 2017 May;124[5]:604-8).
But Dr. Petri contended that concerns about excessive HCQ dosages are overblown. At the meeting, she reported data showing a different perspective on the retinopathy risk of patients on chronic HCQ treatment. In a prospective series of 477 SLE patients on chronic HCQ treatment and followed at Johns Hopkins, the incidence of retinopathy was 10% among patients on treatment for 16 or more years, she reported in a talk at the meeting (Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2897).
A 10% retinopathy rate after 16 or more years on treatment “sounds a lot safer to patients” than rates as high as 30% or 50% that were reported in the JAMA Opthalmology report from 2014, Dr. Petri said. “There is a danger relying on one retrospective study,” she warned. In addition, the 10% risk for retinopathy is “manageable” when patients receive regular screening that produces early detection of retinal damage.
“There has been acceptance of suboptimal dosing of HCQ when discussion has only been about safety, not about efficacy. We need to put the risks into perspective and stop scaring patients.”
Dr. Petri presented her recommendations for treating SLE patients with HCQ: Treat with dosages as high as 6.5 mg/kg but without exceeding 400 mg/day, and cut the dosage for patients with renal insufficiency or failure, those with liver disease, or the elderly. In addition, Dr. Petri endorsed monitoring blood levels of HCQ. Data she reported at the meeting showed a roughly fourfold higher rate of retinopathy among patients who had a maximum HCQ blood level of 1,733 ng/mL or higher when compared with patients whose maximum level remained at 1,194 ng/mL or lower. Clinicians could use blood levels of HCQ to better focus screening and its intensity, she said. “We should embrace monitoring HCQ blood levels.”
Dr. Petri has been a consultant to Amgen, Exagen, GlaxoSmithKline, Inova Diagnostics, Janssen, Lilly, Merck, Novartis, Quintiles, and EMD Serono, and she has received research funding from AstraZeneca and Exagen. Dr. Rosenbaum has been a consultant to AbbVie, Eyevensys, Gilead, Janssen, Novartis, Regeneron, and Roche, and has received research funding from Pfizer.
CHICAGO – The dosage of hydroxychloroquine (HCQ) for treating patients with systemic lupus erythematosus (SLE) is often overly influenced by fear that the drug could cause blindness, Michelle A. Petri, MD, said at the annual meeting of the American College of Rheumatology.
HCQ “is the most important drug we have to treat lupus. It’s the only treatment shown to improve survival of lupus patients. There is no reason to make patients afraid of this very important drug. I am very concerned that fear of blindness is causing our patients to be less adherent” or making them receive an inadequate dosage, said Dr. Petri, a professor of medicine and the director of the Lupus Center at Johns Hopkins University in Baltimore. “I have had no patients who went blind on HCQ. A few patients developed retinopathy, but none went blind.”
Dr. Petri spoke about experiences with some of her SLE patients who were frightened by what an ophthalmologist told them about the retinal effects of HCQ and had their dosage of the drug unilaterally cut by the ophthalmologist.
“The message we should give patients is that retinopathy is a real complication that can happen, but usually not until after 16 years of treatment with HCQ, and we will work together to make sure you are regularly screened so that, if retinopathy developed, we would pick it up early and you’ll remain asymptomatic,” she said. ”We need to put the risk into perspective for our patients.”
Reports differ on the incidence of retinopathy in SLE patients on long-term HCQ treatment. During the session in which Dr. Petri spoke, James T. Rosenbaum, MD, cited a seminal report from 2014 that tracked 2,361 U.S. patients treated with HCQ daily for at least 5 years with regular retinal follow-up. The results showed a steady, cumulative increase in patients who developed retinopathy, an increase that was also dose dependent. For example, patients who received daily dosage of 5-5.9 mg/kg and took the drug for 20 or more years had a cumulative retinopathy incidence of 30% (JAMA Opthalmol. 2014 Dec;132[12]:1453-60). For patients on higher dosages, the cumulative risk at 20 years or longer jumped above 50%.
The findings from this study led directly to the most recent recommendations from the American Academy of Ophthalmology for retinopathy screening for patients on chronic HCQ treatment, said Dr. Rosenbaum, a professor of medicine and opthalmology at Oregon Health & Science University in Portland. The recommendations called for a dosage cap of less than 5 mg/kg real weight, a baseline retinal examination, and then at least annual follow-up examinations starting after 5 years of daily HCQ use, ideally using both automated visual fields and spectral-domain optical coherence tomography (Ophthalmology. 2016 June;123[6]:1386-94). The recommendations also noted that the presence of retinopathy risk factors, including renal disease or concomitant tamoxifen use, warrant starting screening at 5 years or sooner on HCQ.
Clinicians have often exceeded recommended dosage guidelines. Dr. Rosenbaum cited a 2017 report from one U.S. health care system that reviewed the treatment of 554 patients on HCQ and found that roughly half were overdosed in their starting regimen based on prevailing treatment recommendations (Opthalmology. 2017 May;124[5]:604-8).
But Dr. Petri contended that concerns about excessive HCQ dosages are overblown. At the meeting, she reported data showing a different perspective on the retinopathy risk of patients on chronic HCQ treatment. In a prospective series of 477 SLE patients on chronic HCQ treatment and followed at Johns Hopkins, the incidence of retinopathy was 10% among patients on treatment for 16 or more years, she reported in a talk at the meeting (Arthritis Rheumatol. 2018;70[Suppl 10]: Abstract 2897).
A 10% retinopathy rate after 16 or more years on treatment “sounds a lot safer to patients” than rates as high as 30% or 50% that were reported in the JAMA Opthalmology report from 2014, Dr. Petri said. “There is a danger relying on one retrospective study,” she warned. In addition, the 10% risk for retinopathy is “manageable” when patients receive regular screening that produces early detection of retinal damage.
“There has been acceptance of suboptimal dosing of HCQ when discussion has only been about safety, not about efficacy. We need to put the risks into perspective and stop scaring patients.”
Dr. Petri presented her recommendations for treating SLE patients with HCQ: Treat with dosages as high as 6.5 mg/kg but without exceeding 400 mg/day, and cut the dosage for patients with renal insufficiency or failure, those with liver disease, or the elderly. In addition, Dr. Petri endorsed monitoring blood levels of HCQ. Data she reported at the meeting showed a roughly fourfold higher rate of retinopathy among patients who had a maximum HCQ blood level of 1,733 ng/mL or higher when compared with patients whose maximum level remained at 1,194 ng/mL or lower. Clinicians could use blood levels of HCQ to better focus screening and its intensity, she said. “We should embrace monitoring HCQ blood levels.”
Dr. Petri has been a consultant to Amgen, Exagen, GlaxoSmithKline, Inova Diagnostics, Janssen, Lilly, Merck, Novartis, Quintiles, and EMD Serono, and she has received research funding from AstraZeneca and Exagen. Dr. Rosenbaum has been a consultant to AbbVie, Eyevensys, Gilead, Janssen, Novartis, Regeneron, and Roche, and has received research funding from Pfizer.
REPORTING FROM THE ACR ANNUAL MEETING
Tofacitinib impresses in first trial for dermatomyositis
CHICAGO – Oral tofacitinib demonstrated strong clinical efficacy and good safety in the first-ever formal study of a Janus kinase inhibitor in patients with active, treatment-resistant dermatomyositis, Julie J. Paik, MD, reported at the annual meeting of the American College of Rheumatology.
Based upon the encouraging results of this small, open-label, proof-of-concept study, a larger randomized controlled trial is being planned, according to Dr. Paik, a rheumatologist at Johns Hopkins University in Baltimore.
The study included 10 dermatomyositis patients enrolled at the Johns Hopkins Myositis Clinic. All had previously failed at least two steroid-sparing drugs and/or high-dose steroids. After first going off all steroid-sparing agents and being limited to a maximum of 20 mg/day of prednisone, the participants were placed on 11 mg of open-label, extended-release tofacitinib (Xeljanz XR) once daily. Dr. Paik only reported results in 9 patients because the 10th hadn’t yet reached the 12-week mark.
The primary outcome was the rate of achievement of significant improvement at week 12 as defined using the validated International Myositis Assessment and Clinical Studies (IMACS) criteria, which require at least a 20% improvement in three of six core set measures coupled with no more than two measures worsening by 25% or more. By this standard, all nine patients met the primary endpoint. Five were rated as showing moderate improvement, and the other four demonstrated minimal improvement, based on the Total Improvement Score of the Myositis Response criteria. The median Total Improvement Score was 40, indicative of at least moderate improvement.
The mean CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index) activity score – a key secondary endpoint – improved from 28 at baseline to 9.5 at week 12, which translates to a shift from moderate or severe disease to mild disease.
Levels of the alpha-chemokines CXCL9 and CXCL10, which are expressed in muscle affected by idiopathic inflammatory myopathies such as dermatomyositis, declined strongly over the course of 12 weeks of treatment to an extent that was just shy of statistical significance.
Myositis antibody titers didn’t change in response to tofacitinib therapy. Of note, six patients were positive for antitranscriptional intermediary factor 1-gamma, and five of the six were moderate responders to JAK inhibitor therapy.
Four patients were on 20 mg/day of prednisone at baseline; three of the four were able to go off steroids altogether over the course of 12 weeks.
The treatment was well tolerated, with no serious adverse events.
Asked if she thought 11 mg/day of tofacitinib was the right dose for this population of refractory dermatomyositis patients, Dr. Paik replied, “We’re not sure we have the right dose. We had one patient who didn’t have as robust a response, and I really wonder, if we gave her a higher dose, it would have made a difference.”
Extended-release tofacitinib at 11 mg/day is the approved dose for rheumatoid arthritis and psoriatic arthritis. However, 20 mg/day is approved for patients with ulcerative colitis, and Dr. Paik is lobbying for inclusion of a higher-dose arm in the randomized, controlled trial.
Prior to this formal proof-of-concept study, which was funded by Pfizer, the experience with tofacitinib in refractory dermatomyositis was limited to anecdotal case reports.
Dr. Paik reported having no financial conflicts.
SOURCE: Paik JJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L02.
CHICAGO – Oral tofacitinib demonstrated strong clinical efficacy and good safety in the first-ever formal study of a Janus kinase inhibitor in patients with active, treatment-resistant dermatomyositis, Julie J. Paik, MD, reported at the annual meeting of the American College of Rheumatology.
Based upon the encouraging results of this small, open-label, proof-of-concept study, a larger randomized controlled trial is being planned, according to Dr. Paik, a rheumatologist at Johns Hopkins University in Baltimore.
The study included 10 dermatomyositis patients enrolled at the Johns Hopkins Myositis Clinic. All had previously failed at least two steroid-sparing drugs and/or high-dose steroids. After first going off all steroid-sparing agents and being limited to a maximum of 20 mg/day of prednisone, the participants were placed on 11 mg of open-label, extended-release tofacitinib (Xeljanz XR) once daily. Dr. Paik only reported results in 9 patients because the 10th hadn’t yet reached the 12-week mark.
The primary outcome was the rate of achievement of significant improvement at week 12 as defined using the validated International Myositis Assessment and Clinical Studies (IMACS) criteria, which require at least a 20% improvement in three of six core set measures coupled with no more than two measures worsening by 25% or more. By this standard, all nine patients met the primary endpoint. Five were rated as showing moderate improvement, and the other four demonstrated minimal improvement, based on the Total Improvement Score of the Myositis Response criteria. The median Total Improvement Score was 40, indicative of at least moderate improvement.
The mean CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index) activity score – a key secondary endpoint – improved from 28 at baseline to 9.5 at week 12, which translates to a shift from moderate or severe disease to mild disease.
Levels of the alpha-chemokines CXCL9 and CXCL10, which are expressed in muscle affected by idiopathic inflammatory myopathies such as dermatomyositis, declined strongly over the course of 12 weeks of treatment to an extent that was just shy of statistical significance.
Myositis antibody titers didn’t change in response to tofacitinib therapy. Of note, six patients were positive for antitranscriptional intermediary factor 1-gamma, and five of the six were moderate responders to JAK inhibitor therapy.
Four patients were on 20 mg/day of prednisone at baseline; three of the four were able to go off steroids altogether over the course of 12 weeks.
The treatment was well tolerated, with no serious adverse events.
Asked if she thought 11 mg/day of tofacitinib was the right dose for this population of refractory dermatomyositis patients, Dr. Paik replied, “We’re not sure we have the right dose. We had one patient who didn’t have as robust a response, and I really wonder, if we gave her a higher dose, it would have made a difference.”
Extended-release tofacitinib at 11 mg/day is the approved dose for rheumatoid arthritis and psoriatic arthritis. However, 20 mg/day is approved for patients with ulcerative colitis, and Dr. Paik is lobbying for inclusion of a higher-dose arm in the randomized, controlled trial.
Prior to this formal proof-of-concept study, which was funded by Pfizer, the experience with tofacitinib in refractory dermatomyositis was limited to anecdotal case reports.
Dr. Paik reported having no financial conflicts.
SOURCE: Paik JJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L02.
CHICAGO – Oral tofacitinib demonstrated strong clinical efficacy and good safety in the first-ever formal study of a Janus kinase inhibitor in patients with active, treatment-resistant dermatomyositis, Julie J. Paik, MD, reported at the annual meeting of the American College of Rheumatology.
Based upon the encouraging results of this small, open-label, proof-of-concept study, a larger randomized controlled trial is being planned, according to Dr. Paik, a rheumatologist at Johns Hopkins University in Baltimore.
The study included 10 dermatomyositis patients enrolled at the Johns Hopkins Myositis Clinic. All had previously failed at least two steroid-sparing drugs and/or high-dose steroids. After first going off all steroid-sparing agents and being limited to a maximum of 20 mg/day of prednisone, the participants were placed on 11 mg of open-label, extended-release tofacitinib (Xeljanz XR) once daily. Dr. Paik only reported results in 9 patients because the 10th hadn’t yet reached the 12-week mark.
The primary outcome was the rate of achievement of significant improvement at week 12 as defined using the validated International Myositis Assessment and Clinical Studies (IMACS) criteria, which require at least a 20% improvement in three of six core set measures coupled with no more than two measures worsening by 25% or more. By this standard, all nine patients met the primary endpoint. Five were rated as showing moderate improvement, and the other four demonstrated minimal improvement, based on the Total Improvement Score of the Myositis Response criteria. The median Total Improvement Score was 40, indicative of at least moderate improvement.
The mean CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index) activity score – a key secondary endpoint – improved from 28 at baseline to 9.5 at week 12, which translates to a shift from moderate or severe disease to mild disease.
Levels of the alpha-chemokines CXCL9 and CXCL10, which are expressed in muscle affected by idiopathic inflammatory myopathies such as dermatomyositis, declined strongly over the course of 12 weeks of treatment to an extent that was just shy of statistical significance.
Myositis antibody titers didn’t change in response to tofacitinib therapy. Of note, six patients were positive for antitranscriptional intermediary factor 1-gamma, and five of the six were moderate responders to JAK inhibitor therapy.
Four patients were on 20 mg/day of prednisone at baseline; three of the four were able to go off steroids altogether over the course of 12 weeks.
The treatment was well tolerated, with no serious adverse events.
Asked if she thought 11 mg/day of tofacitinib was the right dose for this population of refractory dermatomyositis patients, Dr. Paik replied, “We’re not sure we have the right dose. We had one patient who didn’t have as robust a response, and I really wonder, if we gave her a higher dose, it would have made a difference.”
Extended-release tofacitinib at 11 mg/day is the approved dose for rheumatoid arthritis and psoriatic arthritis. However, 20 mg/day is approved for patients with ulcerative colitis, and Dr. Paik is lobbying for inclusion of a higher-dose arm in the randomized, controlled trial.
Prior to this formal proof-of-concept study, which was funded by Pfizer, the experience with tofacitinib in refractory dermatomyositis was limited to anecdotal case reports.
Dr. Paik reported having no financial conflicts.
SOURCE: Paik JJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L02.
REPORTING FROM THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Among patients with refractory dermatomyositis, the mean Cutaneous Dermatomyositis Disease Area and Severity Index activity score improved from 28 at baseline to 9.5 after 12 weeks on oral tofacitinib.
Study details: This first-in-class, open-label, 12-week study included 10 patients with refractory dermatomyositis placed on extended-release tofacitinib at 11 mg once daily.
Disclosures: The presenter reported having no financial conflicts regarding the study, sponsored by Pfizer.
Source: Paik JJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L02