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VIDEO: Statins cut mortality in ankylosing spondylitis, psoriatic arthritis
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ACR ANNUAL MEETING
Canakinumab controls periodic fever syndromes in post-flare and maintenance dosing
WASHINGTON – Prolonged dosing with canakinumab, an anti-interleukin-1beta monoclonal antibody, confirmed its efficacy in controlling flares in three rare autoinflammatory diseases grouped as periodic fever syndromes: familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and TNF receptor–associated periodic syndrome.
“Colchicine is effective in the majority of patients with FMF [familial Mediterranean fever]. However, patients with resistance to colchicine and patients with HIDS/MKD [hyperimmunoglobulin D syndrome/mevalonate kinase deficiency] or TRAPS [TNF receptor–associated periodic syndrome] have no available therapy until now. The diseases have different mechanisms and different genetic causes, but overlapping and different clinical features and a common mediator. They are all characterized by recurrent fever, joint pain, and involvement of various organs. In addition to greatly affecting the quality of life, the major complication is amyloidosis. Clinical studies and animal studies suggested that IL-1beta was involved in the pathogenesis of these diseases, and canakinumab [Ilaris] targets IL-1beta,” explained Fabrizio De Benedetti, MD, a pediatric rheumatologist at Bambino Gesu Children’s Hospital in Rome.
Following the 16-week, double-blind, randomized treatment phase of the CLUSTER trial, responders at the standard dose of 150 mg (or 2 mg/kg for patients weighing 40 kg or less) every 4 weeks were rerandomized in a 24-week randomized withdrawal phase, followed by a 72-week open-label phase.
At the annual meeting of the American College of Rheumatology, Dr. De Benedetti presented results of the 24-week randomized withdrawal phase in which 42 patients who showed complete response (defined as resolution of index flare and no new flare in the 16 week duration of the randomized controlled phase of the study) after being initially randomized to canakinumab 150 mg every 4 weeks were then rerandomized 1:1 to canakinumab 150 mg every 8 weeks versus placebo. He also presented results for patients who failed placebo during the initial 16-week randomized treatment period; went to open-label rescue treatment with canakinumab; and then, in the 24-week maintenance period, began taking open-label canakinumab 150 mg every 8 weeks. Overall, 160 patients had evaluable data for the maintenance dosing period.
The end point of this phase on a maintenance dose of canakinumab 150 mg every 8 weeks was the proportion of patients who maintained disease control and had no flare, meaning Physician Global Assessment was less than 2 and C-reactive protein was less than 30 mg/L between week 16 and week 40 after rerandomization. Patients who experienced a flare during this time could be escalated up to canakinumab 300 mg every 4 weeks.
At week 40, the proportion of responders was higher in the canakinumab-treated group, compared with placebo, at 68% versus 27%, respectively, but the difference was not statistically significant, Dr. De Benedetti reported.
The percentage of patients on canakinumab who maintained their response by week 40 was higher in each disease group, compared with placebo, but not to a statistically significant extent. The response rates were 78% vs. 30% for FMF; 50% vs. 14% for HIDS/MKD; and 75% vs. 40% for TRAPS. Only 10% of FMF and 8% of TRAPS patients required titration of canakinumab up to 300 mg every 4 weeks, compared with 29% of HIDS/MKD patients, he said.
No new safety findings were reported and there was no accumulation of toxicity. A total of 139 adverse events was reported among all patients in the placebo arm (including the double-blind and prolonged dosing phases), and 8 of these were deemed serious adverse events. The rate of serious adverse events was 85 per 100 patient-years. Among canakinumab-treated patients, the rates of serious adverse events were 34 per 100 patient-years for FMF, 34 per 100 for HIDS/MKD, and 19 per 100 for TRAPS.
“The results of this trial confirm the long-term efficacy of canakinumab in these rare diseases and provide information on the long-term dose needed to control disease, with about half of the patients with FMF or TRAPS and about one-third of those with HIDS/MKD showing no flare at a prolonged dose of 150 mg every 8 weeks,” Dr. De Benedetti said.
The study was supported by Novartis, which markets canakinumab. Dr. De Benedetti disclosed financial ties with Novartis, Pfizer, AbbVie, Roche, Novimmune, and Bristol-Myers Squibb.
WASHINGTON – Prolonged dosing with canakinumab, an anti-interleukin-1beta monoclonal antibody, confirmed its efficacy in controlling flares in three rare autoinflammatory diseases grouped as periodic fever syndromes: familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and TNF receptor–associated periodic syndrome.
“Colchicine is effective in the majority of patients with FMF [familial Mediterranean fever]. However, patients with resistance to colchicine and patients with HIDS/MKD [hyperimmunoglobulin D syndrome/mevalonate kinase deficiency] or TRAPS [TNF receptor–associated periodic syndrome] have no available therapy until now. The diseases have different mechanisms and different genetic causes, but overlapping and different clinical features and a common mediator. They are all characterized by recurrent fever, joint pain, and involvement of various organs. In addition to greatly affecting the quality of life, the major complication is amyloidosis. Clinical studies and animal studies suggested that IL-1beta was involved in the pathogenesis of these diseases, and canakinumab [Ilaris] targets IL-1beta,” explained Fabrizio De Benedetti, MD, a pediatric rheumatologist at Bambino Gesu Children’s Hospital in Rome.
Following the 16-week, double-blind, randomized treatment phase of the CLUSTER trial, responders at the standard dose of 150 mg (or 2 mg/kg for patients weighing 40 kg or less) every 4 weeks were rerandomized in a 24-week randomized withdrawal phase, followed by a 72-week open-label phase.
At the annual meeting of the American College of Rheumatology, Dr. De Benedetti presented results of the 24-week randomized withdrawal phase in which 42 patients who showed complete response (defined as resolution of index flare and no new flare in the 16 week duration of the randomized controlled phase of the study) after being initially randomized to canakinumab 150 mg every 4 weeks were then rerandomized 1:1 to canakinumab 150 mg every 8 weeks versus placebo. He also presented results for patients who failed placebo during the initial 16-week randomized treatment period; went to open-label rescue treatment with canakinumab; and then, in the 24-week maintenance period, began taking open-label canakinumab 150 mg every 8 weeks. Overall, 160 patients had evaluable data for the maintenance dosing period.
The end point of this phase on a maintenance dose of canakinumab 150 mg every 8 weeks was the proportion of patients who maintained disease control and had no flare, meaning Physician Global Assessment was less than 2 and C-reactive protein was less than 30 mg/L between week 16 and week 40 after rerandomization. Patients who experienced a flare during this time could be escalated up to canakinumab 300 mg every 4 weeks.
At week 40, the proportion of responders was higher in the canakinumab-treated group, compared with placebo, at 68% versus 27%, respectively, but the difference was not statistically significant, Dr. De Benedetti reported.
The percentage of patients on canakinumab who maintained their response by week 40 was higher in each disease group, compared with placebo, but not to a statistically significant extent. The response rates were 78% vs. 30% for FMF; 50% vs. 14% for HIDS/MKD; and 75% vs. 40% for TRAPS. Only 10% of FMF and 8% of TRAPS patients required titration of canakinumab up to 300 mg every 4 weeks, compared with 29% of HIDS/MKD patients, he said.
No new safety findings were reported and there was no accumulation of toxicity. A total of 139 adverse events was reported among all patients in the placebo arm (including the double-blind and prolonged dosing phases), and 8 of these were deemed serious adverse events. The rate of serious adverse events was 85 per 100 patient-years. Among canakinumab-treated patients, the rates of serious adverse events were 34 per 100 patient-years for FMF, 34 per 100 for HIDS/MKD, and 19 per 100 for TRAPS.
“The results of this trial confirm the long-term efficacy of canakinumab in these rare diseases and provide information on the long-term dose needed to control disease, with about half of the patients with FMF or TRAPS and about one-third of those with HIDS/MKD showing no flare at a prolonged dose of 150 mg every 8 weeks,” Dr. De Benedetti said.
The study was supported by Novartis, which markets canakinumab. Dr. De Benedetti disclosed financial ties with Novartis, Pfizer, AbbVie, Roche, Novimmune, and Bristol-Myers Squibb.
WASHINGTON – Prolonged dosing with canakinumab, an anti-interleukin-1beta monoclonal antibody, confirmed its efficacy in controlling flares in three rare autoinflammatory diseases grouped as periodic fever syndromes: familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and TNF receptor–associated periodic syndrome.
“Colchicine is effective in the majority of patients with FMF [familial Mediterranean fever]. However, patients with resistance to colchicine and patients with HIDS/MKD [hyperimmunoglobulin D syndrome/mevalonate kinase deficiency] or TRAPS [TNF receptor–associated periodic syndrome] have no available therapy until now. The diseases have different mechanisms and different genetic causes, but overlapping and different clinical features and a common mediator. They are all characterized by recurrent fever, joint pain, and involvement of various organs. In addition to greatly affecting the quality of life, the major complication is amyloidosis. Clinical studies and animal studies suggested that IL-1beta was involved in the pathogenesis of these diseases, and canakinumab [Ilaris] targets IL-1beta,” explained Fabrizio De Benedetti, MD, a pediatric rheumatologist at Bambino Gesu Children’s Hospital in Rome.
Following the 16-week, double-blind, randomized treatment phase of the CLUSTER trial, responders at the standard dose of 150 mg (or 2 mg/kg for patients weighing 40 kg or less) every 4 weeks were rerandomized in a 24-week randomized withdrawal phase, followed by a 72-week open-label phase.
At the annual meeting of the American College of Rheumatology, Dr. De Benedetti presented results of the 24-week randomized withdrawal phase in which 42 patients who showed complete response (defined as resolution of index flare and no new flare in the 16 week duration of the randomized controlled phase of the study) after being initially randomized to canakinumab 150 mg every 4 weeks were then rerandomized 1:1 to canakinumab 150 mg every 8 weeks versus placebo. He also presented results for patients who failed placebo during the initial 16-week randomized treatment period; went to open-label rescue treatment with canakinumab; and then, in the 24-week maintenance period, began taking open-label canakinumab 150 mg every 8 weeks. Overall, 160 patients had evaluable data for the maintenance dosing period.
The end point of this phase on a maintenance dose of canakinumab 150 mg every 8 weeks was the proportion of patients who maintained disease control and had no flare, meaning Physician Global Assessment was less than 2 and C-reactive protein was less than 30 mg/L between week 16 and week 40 after rerandomization. Patients who experienced a flare during this time could be escalated up to canakinumab 300 mg every 4 weeks.
At week 40, the proportion of responders was higher in the canakinumab-treated group, compared with placebo, at 68% versus 27%, respectively, but the difference was not statistically significant, Dr. De Benedetti reported.
The percentage of patients on canakinumab who maintained their response by week 40 was higher in each disease group, compared with placebo, but not to a statistically significant extent. The response rates were 78% vs. 30% for FMF; 50% vs. 14% for HIDS/MKD; and 75% vs. 40% for TRAPS. Only 10% of FMF and 8% of TRAPS patients required titration of canakinumab up to 300 mg every 4 weeks, compared with 29% of HIDS/MKD patients, he said.
No new safety findings were reported and there was no accumulation of toxicity. A total of 139 adverse events was reported among all patients in the placebo arm (including the double-blind and prolonged dosing phases), and 8 of these were deemed serious adverse events. The rate of serious adverse events was 85 per 100 patient-years. Among canakinumab-treated patients, the rates of serious adverse events were 34 per 100 patient-years for FMF, 34 per 100 for HIDS/MKD, and 19 per 100 for TRAPS.
“The results of this trial confirm the long-term efficacy of canakinumab in these rare diseases and provide information on the long-term dose needed to control disease, with about half of the patients with FMF or TRAPS and about one-third of those with HIDS/MKD showing no flare at a prolonged dose of 150 mg every 8 weeks,” Dr. De Benedetti said.
The study was supported by Novartis, which markets canakinumab. Dr. De Benedetti disclosed financial ties with Novartis, Pfizer, AbbVie, Roche, Novimmune, and Bristol-Myers Squibb.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: At week 40, the proportion of responders was higher in the canakinumab-treated group (68%), compared with placebo (27%), but the difference was not statistically significant.
Data source: A phase III, randomized, double-blind, 16-week, placebo-controlled trial of 181 patients, followed by a 24-week withdrawal phase rerandomizing 42 responders, with all other patients continuing on canakinumab.
Disclosures: The study was supported by Novartis, which markets canakinumab. Dr. De Benedetti disclosed financial ties with Novartis, Pfizer, AbbVie, Roche, Novimmune, and Bristol-Myers Squibb.
VIDEO: Urate lowering therapy improved kidney function
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Urate lowering therapy improved kidney function in patients with chronic kidney disease (CKD), according to a large retrospective study presented at the annual meeting of the American College of Rheumatology. Moreover, patients with CKD stage 3 derived the most benefit from urate lowering therapy, and those with CKD stage 2 also benefited to a lesser degree. Patients with CKD stage 4 had no benefit from urate lowering therapy.
“Two years ago we showed that urate lowering therapy did not worsen kidney function in patients with chronic kidney disease. This study shows that their kidney function improved [with urate lowering therapy],” said Gerald D. Levy, MD, MBA, a rheumatologist at Kaiser Permanente of Southern California, Downey, Calif.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of above 7 mg/dL and CKD Stages 2, 3, and 4 at the index date, defined as the first time this test result was reported. Patients were drawn from the Kaiser Permanente database and were treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on urate lowering therapy and 10,061 were not on urate lowering therapy. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on urate lowering therapy. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve sUA goal, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate lowering therapy,” he stated. “Stage 4 CKD is too late.”
Dr. Levy discussed the findings in a video interview during the meeting.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ACR ANNUAL MEETING
Long-term remission maintenance in ANCA-associated vasculitis leans toward rituximab over azathioprine
WASHINGTON – Rituximab was superior to azathioprine as maintenance therapy for antineutrophil cytoplasmic antibody–associated vasculitis over long-term follow-up of the MAINRITSAN trial. At 60 months, rituximab significantly improved overall survival and relapse-free survival, compared with azathioprine.
At 60 months, overall survival (OS) rates were 100% for rituximab (Rituxan) versus 93% for azathioprine (P = .045), and relapse-free survival (RFS) rates were 57.9% versus 37.3%, respectively (P = .012).
These long-term maintenance results build on the primary results of MAINRITSAN that were previously published in 2014 (N Engl J Med. 2014;Nov 6;371[19]:1771-80). The primary results showed the superiority of rituximab maintenance therapy versus the then-gold standard azathioprine in maintaining antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) remission at 28 months following induction therapy with a cyclophosphamide/glucocorticoid regimen.
“Following publication of the primary results, some uncertainties remained as to the duration of remission on rituximab. There is a need for therapy that can prevent relapse over the longer term,” lead author Benjamin Terrier, MD, of the National Referral Center for Rare Systemic Autoimmune Diseases at Cochin Hospital and Paris Descartes University in France, said in his presentation of the long-term follow-up data at the annual meeting of the American College of Rheumatology.
The follow-up results indicate that “over the long term, despite late relapses after the 28-month initial follow-up period, maintenance therapy with rituximab remained significantly superior to azathioprine to maintain remission at 60 months and was associated with better survival,” Dr. Terrier said.
The study included 115 newly diagnosed or relapsing patients with AAV (granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis). Of these, 80% were newly diagnosed. After achieving remission on induction therapy, patients were randomized to rituximab infusion 500 mg on day 1, day 15, and 5.5 months later, then every 6 months for 18 months or to azathioprine for 22 months.
The investigators collected data prospectively on major and minor relapses and adverse events, using a Q-TWIST (Quality Adjusted Time Without Symptoms and Toxicity) analysis to show the trade-off between toxicity and disease activity.
For all relapses, major and minor, rituximab maintained superiority over azathioprine at 60 months. There were 24 events in the rituximab arm: 11 minor relapses and 13 major relapses. There were 36 events in the azathioprine arm: 10 minor relapses, 25 major relapses, and 1 death. Major RFS survival rates were 71.9% versus 49.4%, respectively (P = .003).
“There was an absolute difference of 12 months favoring rituximab for RFS,” Dr. Terrier said.
Serious infections were numerically increased in the rituximab-treated group: 30 compared with 20 in the azathioprine group. Cardiovascular event rates were similar for both groups.
Q-TWIST analysis found significantly longer quality-adjusted time without progression or toxicity in the rituximab arm (P less than .001). The cumulative dose of steroids was comparable between treatment groups.
Six cancers were found in the azathioprine arm (including four skin cancers), compared with two in the rituximab arm.
In the rituximab group, PR3 ANCA positivity or ANCA persistence 12 months after starting rituximab maintenance therapy were associated with higher major relapse rates.
“Combining these two factors allows discerning low relapse rate. Patients negative for ANCA and for PR3 ANCA were at low risk,” Dr. Terrier told the audience. “ANCA monitoring seems to be relevant to guide treatment duration.”
Best rituximab regimen?
A separate study presented at a poster session compared the systemic regimen used in MAINRITSAN (as a control group) versus an experimental regimen of fixed 500-mg rituximab infusions on day 0 post randomization and then every 3 months until month 18, based on ANCA status/titer and/or circulating CD19 B-cell reappearance. The open-label, randomized study included 163 patients with granulomatosis with polyangiitis or microscopic polyangiitis in complete remission after induction therapy with glucocorticoids and cyclophosphamide or rituximab or methotrexate.
At 28 months, the relapse rate was 8% in the control arm and 14% in the experimental arm, a difference that was not statistically significant.
“We found no difference in the primary endpoint of relapse between the two regimens, but the experimental arm received fewer infusions. From this study, we cannot make a strong recommendation for the experimental regimen, but we think it is better, because there is less cumulative exposure to rituximab,” stated lead author Pierre Charles, MD, also of Cochin Hospital.
Both studies were funded by Hoffman-LaRoche. Dr. Terrier and Dr. Charles disclosed financial support from Hoffman-LaRoche.
Over the long term, patients initially randomized to rituximab maintenance therapy in the initial phase of the MAINRITSAN trial continued to be more likely to remain in remission than were those who had been randomized to azathioprine. The maintenance therapy data for rituximab look better than for azathioprine.
In clinical practice, individualizing the timing of repeat rituximab may be favorable for remission maintenance rather than having the same fixed dose for all comers, as was used in the MAINRITSAN trial.
By tailoring therapy, it may be possible to use less medication. If patients’ B cells remain depleted and ANCA is stable, flare is unlikely in the next 3 months, but if B cells are reconstituting, particularly in concert with a rising ANCA, I would generally administer a “remission maintenance” dose of rituximab, particularly in an individual who has had relapsing disease in the past. Perhaps patients could use less cumulative rituximab if these parameters are used to make treatment decisions. The poster presentation by Pierre Charles, MD, suggested that this approach indeed is feasible.
Robert F. Spiera, MD, is director of the Scleroderma, Vasculitis, & Myositis Center at the Hospital for Special Surgery, New York. He is also professor of clinical medicine at Cornell University, New York. He made these comments in an interview. Dr. Spiera has received research funding and consulting fees from Roche/Genentech, which markets rituximab.
Over the long term, patients initially randomized to rituximab maintenance therapy in the initial phase of the MAINRITSAN trial continued to be more likely to remain in remission than were those who had been randomized to azathioprine. The maintenance therapy data for rituximab look better than for azathioprine.
In clinical practice, individualizing the timing of repeat rituximab may be favorable for remission maintenance rather than having the same fixed dose for all comers, as was used in the MAINRITSAN trial.
By tailoring therapy, it may be possible to use less medication. If patients’ B cells remain depleted and ANCA is stable, flare is unlikely in the next 3 months, but if B cells are reconstituting, particularly in concert with a rising ANCA, I would generally administer a “remission maintenance” dose of rituximab, particularly in an individual who has had relapsing disease in the past. Perhaps patients could use less cumulative rituximab if these parameters are used to make treatment decisions. The poster presentation by Pierre Charles, MD, suggested that this approach indeed is feasible.
Robert F. Spiera, MD, is director of the Scleroderma, Vasculitis, & Myositis Center at the Hospital for Special Surgery, New York. He is also professor of clinical medicine at Cornell University, New York. He made these comments in an interview. Dr. Spiera has received research funding and consulting fees from Roche/Genentech, which markets rituximab.
Over the long term, patients initially randomized to rituximab maintenance therapy in the initial phase of the MAINRITSAN trial continued to be more likely to remain in remission than were those who had been randomized to azathioprine. The maintenance therapy data for rituximab look better than for azathioprine.
In clinical practice, individualizing the timing of repeat rituximab may be favorable for remission maintenance rather than having the same fixed dose for all comers, as was used in the MAINRITSAN trial.
By tailoring therapy, it may be possible to use less medication. If patients’ B cells remain depleted and ANCA is stable, flare is unlikely in the next 3 months, but if B cells are reconstituting, particularly in concert with a rising ANCA, I would generally administer a “remission maintenance” dose of rituximab, particularly in an individual who has had relapsing disease in the past. Perhaps patients could use less cumulative rituximab if these parameters are used to make treatment decisions. The poster presentation by Pierre Charles, MD, suggested that this approach indeed is feasible.
Robert F. Spiera, MD, is director of the Scleroderma, Vasculitis, & Myositis Center at the Hospital for Special Surgery, New York. He is also professor of clinical medicine at Cornell University, New York. He made these comments in an interview. Dr. Spiera has received research funding and consulting fees from Roche/Genentech, which markets rituximab.
WASHINGTON – Rituximab was superior to azathioprine as maintenance therapy for antineutrophil cytoplasmic antibody–associated vasculitis over long-term follow-up of the MAINRITSAN trial. At 60 months, rituximab significantly improved overall survival and relapse-free survival, compared with azathioprine.
At 60 months, overall survival (OS) rates were 100% for rituximab (Rituxan) versus 93% for azathioprine (P = .045), and relapse-free survival (RFS) rates were 57.9% versus 37.3%, respectively (P = .012).
These long-term maintenance results build on the primary results of MAINRITSAN that were previously published in 2014 (N Engl J Med. 2014;Nov 6;371[19]:1771-80). The primary results showed the superiority of rituximab maintenance therapy versus the then-gold standard azathioprine in maintaining antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) remission at 28 months following induction therapy with a cyclophosphamide/glucocorticoid regimen.
“Following publication of the primary results, some uncertainties remained as to the duration of remission on rituximab. There is a need for therapy that can prevent relapse over the longer term,” lead author Benjamin Terrier, MD, of the National Referral Center for Rare Systemic Autoimmune Diseases at Cochin Hospital and Paris Descartes University in France, said in his presentation of the long-term follow-up data at the annual meeting of the American College of Rheumatology.
The follow-up results indicate that “over the long term, despite late relapses after the 28-month initial follow-up period, maintenance therapy with rituximab remained significantly superior to azathioprine to maintain remission at 60 months and was associated with better survival,” Dr. Terrier said.
The study included 115 newly diagnosed or relapsing patients with AAV (granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis). Of these, 80% were newly diagnosed. After achieving remission on induction therapy, patients were randomized to rituximab infusion 500 mg on day 1, day 15, and 5.5 months later, then every 6 months for 18 months or to azathioprine for 22 months.
The investigators collected data prospectively on major and minor relapses and adverse events, using a Q-TWIST (Quality Adjusted Time Without Symptoms and Toxicity) analysis to show the trade-off between toxicity and disease activity.
For all relapses, major and minor, rituximab maintained superiority over azathioprine at 60 months. There were 24 events in the rituximab arm: 11 minor relapses and 13 major relapses. There were 36 events in the azathioprine arm: 10 minor relapses, 25 major relapses, and 1 death. Major RFS survival rates were 71.9% versus 49.4%, respectively (P = .003).
“There was an absolute difference of 12 months favoring rituximab for RFS,” Dr. Terrier said.
Serious infections were numerically increased in the rituximab-treated group: 30 compared with 20 in the azathioprine group. Cardiovascular event rates were similar for both groups.
Q-TWIST analysis found significantly longer quality-adjusted time without progression or toxicity in the rituximab arm (P less than .001). The cumulative dose of steroids was comparable between treatment groups.
Six cancers were found in the azathioprine arm (including four skin cancers), compared with two in the rituximab arm.
In the rituximab group, PR3 ANCA positivity or ANCA persistence 12 months after starting rituximab maintenance therapy were associated with higher major relapse rates.
“Combining these two factors allows discerning low relapse rate. Patients negative for ANCA and for PR3 ANCA were at low risk,” Dr. Terrier told the audience. “ANCA monitoring seems to be relevant to guide treatment duration.”
Best rituximab regimen?
A separate study presented at a poster session compared the systemic regimen used in MAINRITSAN (as a control group) versus an experimental regimen of fixed 500-mg rituximab infusions on day 0 post randomization and then every 3 months until month 18, based on ANCA status/titer and/or circulating CD19 B-cell reappearance. The open-label, randomized study included 163 patients with granulomatosis with polyangiitis or microscopic polyangiitis in complete remission after induction therapy with glucocorticoids and cyclophosphamide or rituximab or methotrexate.
At 28 months, the relapse rate was 8% in the control arm and 14% in the experimental arm, a difference that was not statistically significant.
“We found no difference in the primary endpoint of relapse between the two regimens, but the experimental arm received fewer infusions. From this study, we cannot make a strong recommendation for the experimental regimen, but we think it is better, because there is less cumulative exposure to rituximab,” stated lead author Pierre Charles, MD, also of Cochin Hospital.
Both studies were funded by Hoffman-LaRoche. Dr. Terrier and Dr. Charles disclosed financial support from Hoffman-LaRoche.
WASHINGTON – Rituximab was superior to azathioprine as maintenance therapy for antineutrophil cytoplasmic antibody–associated vasculitis over long-term follow-up of the MAINRITSAN trial. At 60 months, rituximab significantly improved overall survival and relapse-free survival, compared with azathioprine.
At 60 months, overall survival (OS) rates were 100% for rituximab (Rituxan) versus 93% for azathioprine (P = .045), and relapse-free survival (RFS) rates were 57.9% versus 37.3%, respectively (P = .012).
These long-term maintenance results build on the primary results of MAINRITSAN that were previously published in 2014 (N Engl J Med. 2014;Nov 6;371[19]:1771-80). The primary results showed the superiority of rituximab maintenance therapy versus the then-gold standard azathioprine in maintaining antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) remission at 28 months following induction therapy with a cyclophosphamide/glucocorticoid regimen.
“Following publication of the primary results, some uncertainties remained as to the duration of remission on rituximab. There is a need for therapy that can prevent relapse over the longer term,” lead author Benjamin Terrier, MD, of the National Referral Center for Rare Systemic Autoimmune Diseases at Cochin Hospital and Paris Descartes University in France, said in his presentation of the long-term follow-up data at the annual meeting of the American College of Rheumatology.
The follow-up results indicate that “over the long term, despite late relapses after the 28-month initial follow-up period, maintenance therapy with rituximab remained significantly superior to azathioprine to maintain remission at 60 months and was associated with better survival,” Dr. Terrier said.
The study included 115 newly diagnosed or relapsing patients with AAV (granulomatosis with polyangiitis, microscopic polyangiitis, or eosinophilic granulomatosis with polyangiitis). Of these, 80% were newly diagnosed. After achieving remission on induction therapy, patients were randomized to rituximab infusion 500 mg on day 1, day 15, and 5.5 months later, then every 6 months for 18 months or to azathioprine for 22 months.
The investigators collected data prospectively on major and minor relapses and adverse events, using a Q-TWIST (Quality Adjusted Time Without Symptoms and Toxicity) analysis to show the trade-off between toxicity and disease activity.
For all relapses, major and minor, rituximab maintained superiority over azathioprine at 60 months. There were 24 events in the rituximab arm: 11 minor relapses and 13 major relapses. There were 36 events in the azathioprine arm: 10 minor relapses, 25 major relapses, and 1 death. Major RFS survival rates were 71.9% versus 49.4%, respectively (P = .003).
“There was an absolute difference of 12 months favoring rituximab for RFS,” Dr. Terrier said.
Serious infections were numerically increased in the rituximab-treated group: 30 compared with 20 in the azathioprine group. Cardiovascular event rates were similar for both groups.
Q-TWIST analysis found significantly longer quality-adjusted time without progression or toxicity in the rituximab arm (P less than .001). The cumulative dose of steroids was comparable between treatment groups.
Six cancers were found in the azathioprine arm (including four skin cancers), compared with two in the rituximab arm.
In the rituximab group, PR3 ANCA positivity or ANCA persistence 12 months after starting rituximab maintenance therapy were associated with higher major relapse rates.
“Combining these two factors allows discerning low relapse rate. Patients negative for ANCA and for PR3 ANCA were at low risk,” Dr. Terrier told the audience. “ANCA monitoring seems to be relevant to guide treatment duration.”
Best rituximab regimen?
A separate study presented at a poster session compared the systemic regimen used in MAINRITSAN (as a control group) versus an experimental regimen of fixed 500-mg rituximab infusions on day 0 post randomization and then every 3 months until month 18, based on ANCA status/titer and/or circulating CD19 B-cell reappearance. The open-label, randomized study included 163 patients with granulomatosis with polyangiitis or microscopic polyangiitis in complete remission after induction therapy with glucocorticoids and cyclophosphamide or rituximab or methotrexate.
At 28 months, the relapse rate was 8% in the control arm and 14% in the experimental arm, a difference that was not statistically significant.
“We found no difference in the primary endpoint of relapse between the two regimens, but the experimental arm received fewer infusions. From this study, we cannot make a strong recommendation for the experimental regimen, but we think it is better, because there is less cumulative exposure to rituximab,” stated lead author Pierre Charles, MD, also of Cochin Hospital.
Both studies were funded by Hoffman-LaRoche. Dr. Terrier and Dr. Charles disclosed financial support from Hoffman-LaRoche.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: At 60 months, overall survival rates were 100% for rituximab versus 93% azathioprine (P = .045) and relapse-free survival rates were 57.9% versus 37.3%, respectively (P = .012).
Data source: 60-month follow-up of a randomized, controlled trial of 115 patients.
Disclosures: Both studies were funded by Hoffman-LaRoche. Dr. Terrier and Dr. Charles each disclosed financial support from Hoffman-LaRoche.
Flare risk lower in early-gout patients treated with urate-lowering therapy
WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.
Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).
The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.
“The reduction in flares with febuxostat is clinically important and statistically significant,” said lead author Nicola Dalbeth, MD, of the University of Auckland (New Zealand). “This is the first clinical trial of [urate-lowering therapy] in patients with early gout. These are patients who would not be treated under current [American College of Rheumatology] guidelines,” which call for urate-lowering therapy if patients are symptomatic and have experienced two or more flares per year.
Dr. Dalbeth presented the study results at a late-breaker session during the annual meeting of the American College of Rheumatology.
The 314 patients were initially randomized to febuxostat 40 mg or placebo. The febuxostat dosage was increased to 80 mg if serum uric acid levels were above target on day 14, and 60 patients had their febuxostat doses increased.
The study was completed by 57% of placebo patients and 59% of febuxostat patients. Baseline characteristics were similar across treatment arms. Mean baseline serum uric acid was about 8.7 mg/dL, mean age was around 50 years, and more than three-quarters of study participants were white. Mean body-mass index was about 32.5, and mild renal impairment was present in 73% of placebo patients and 67% of febuxostat-treated patients.
Based on imaging studies, febuxostat had no significant effect on joint erosion during the observation period, but it reduced synovitis, compared with placebo, she said.
Dr. Dalbeth disclosed relationships with a variety of drug companies, including serving as a consultant for Takeda, the maker of febuxostat (Uloric).
WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.
Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).
The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.
“The reduction in flares with febuxostat is clinically important and statistically significant,” said lead author Nicola Dalbeth, MD, of the University of Auckland (New Zealand). “This is the first clinical trial of [urate-lowering therapy] in patients with early gout. These are patients who would not be treated under current [American College of Rheumatology] guidelines,” which call for urate-lowering therapy if patients are symptomatic and have experienced two or more flares per year.
Dr. Dalbeth presented the study results at a late-breaker session during the annual meeting of the American College of Rheumatology.
The 314 patients were initially randomized to febuxostat 40 mg or placebo. The febuxostat dosage was increased to 80 mg if serum uric acid levels were above target on day 14, and 60 patients had their febuxostat doses increased.
The study was completed by 57% of placebo patients and 59% of febuxostat patients. Baseline characteristics were similar across treatment arms. Mean baseline serum uric acid was about 8.7 mg/dL, mean age was around 50 years, and more than three-quarters of study participants were white. Mean body-mass index was about 32.5, and mild renal impairment was present in 73% of placebo patients and 67% of febuxostat-treated patients.
Based on imaging studies, febuxostat had no significant effect on joint erosion during the observation period, but it reduced synovitis, compared with placebo, she said.
Dr. Dalbeth disclosed relationships with a variety of drug companies, including serving as a consultant for Takeda, the maker of febuxostat (Uloric).
WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.
Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).
The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.
“The reduction in flares with febuxostat is clinically important and statistically significant,” said lead author Nicola Dalbeth, MD, of the University of Auckland (New Zealand). “This is the first clinical trial of [urate-lowering therapy] in patients with early gout. These are patients who would not be treated under current [American College of Rheumatology] guidelines,” which call for urate-lowering therapy if patients are symptomatic and have experienced two or more flares per year.
Dr. Dalbeth presented the study results at a late-breaker session during the annual meeting of the American College of Rheumatology.
The 314 patients were initially randomized to febuxostat 40 mg or placebo. The febuxostat dosage was increased to 80 mg if serum uric acid levels were above target on day 14, and 60 patients had their febuxostat doses increased.
The study was completed by 57% of placebo patients and 59% of febuxostat patients. Baseline characteristics were similar across treatment arms. Mean baseline serum uric acid was about 8.7 mg/dL, mean age was around 50 years, and more than three-quarters of study participants were white. Mean body-mass index was about 32.5, and mild renal impairment was present in 73% of placebo patients and 67% of febuxostat-treated patients.
Based on imaging studies, febuxostat had no significant effect on joint erosion during the observation period, but it reduced synovitis, compared with placebo, she said.
Dr. Dalbeth disclosed relationships with a variety of drug companies, including serving as a consultant for Takeda, the maker of febuxostat (Uloric).
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Early-gout patients given febuxostat had a 29% risk of a flare and placebo-treated patients had a 41% risk of a flare over 2 years, a significant difference.
Data source: Randomized, double-blind, placebo-controlled, phase II study of 314 patients with early gout.
Disclosures: Dr. Dalbeth disclosed relationships with a variety of drug companies, including serving as a consultant for Takeda, the maker of febuxostat (Uloric).
First JAK inhibitor in psoriatic arthritis achieves results similar to adalimumab
WASHINGTON – Tofacitinib demonstrated efficacy comparable to adalimumab in patients with active psoriatic arthritis (PsA) and an inadequate response to conventional disease-modifying antirheumatic drugs in the phase III OPAL Broaden study.
“This is the first study to demonstrate efficacy of a JAK [Janus kinase] inhibitor in PsA,” said lead author Philip J. Mease, MD, of Swedish Medical Center, Seattle. “The primary endpoints were achieved with tofacitinib [Xeljanz] versus placebo. Onset of efficacy of tofacitinib on the ACR20 [the American College of Rheumatology 20% improvement criteria] was observed as early as week 2. Radiographic non-progression rates were low and similar to placebo. Improvement was seen in enthesitis and dactylitis as well as in joint and skin symptoms, and efficacy was maintained through month 12. Tofacitinib is a potential future option for the treatment of PsA.”
The study enrolled 422 patients with active PsA diagnosed within the last 6 months or longer, and all also had plaque psoriasis at screening. The primary endpoint was ACR20 response at 3 months.
Patients were randomized to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab (Humira) 40 mg subcutaneously every 2 weeks, or placebo. At 3 months, placebo patients were re-randomized to tofacitinib 5 mg or 10 mg twice daily. The trial was completed by 372 patients (88.4%).
At baseline, groups had similar demographic and disease characteristics. Patients had a median age just under 50 years, tended to be overweight, and had disease duration that ranged from 5 to 7 years. The majority of patients had enthesitis and dactylitis, and all were on background disease-modifying antirheumatic drugs.
All of the active treatment arms achieved statistically significant rates versus placebo on the primary endpoint of ACR20 response at 3 months: 50% in the tofacitinib 5-mg group, 61% in the tofacitinib 10-mg group, and 52% in the adalimumab group, compared with 33% of placebo-treated patients. ACR20 responses increased out to 12 months in 68%, 70%, and 60%, respectively in the three active treatment arms. At 3 months, ACR50 responses in the three active treatment arms were 28%, 40%, and 33%, respectively, and for ACR70 were 17%, 14%, and 19%.
Health Assessment Questionnaire Disability Index (HAQ-DI) responses were statistically significant for all three active dosing arms, compared with placebo.
“Placebo patients re-randomized to tofacitinib also had good ACR responses at month 12,” Dr. Mease said.
The rate of radiographic non-progression at month 12 was similar in all treatment arms at about 95%, including former placebo patients who switched to tofacitinib.
Skin responses, according to Psoriasis Area and Severity Index (PASI) 75, were 43% for tofacitinib 5 mg twice daily, 44% for tofacitinib 10 mg twice daily, and 39% for adalimumab. At 12 months, the percentage of patients achieving PASI 75 increased for all three treatment arms.
The same pattern was observed for enthesitis and dactylitis.
Minimal disease activity was seen at 3 months in about 25% of all the active treatment arms, and the rates improved at month 12.
There were few discontinuations due to adverse events in any group. Adverse event rates were similar across all treatment arms at month 3, including the placebo arm. The rate of serious adverse events reported at month 12 was 5% for tofacitinib 5 mg twice daily, 2.9% for tofacitinib 10 mg twice daily, 7.8% for adalimumab, and 6% in placebo patients switched to either dose of tofacitinib at month 3.
Laboratory changes were similar to those reported with tofacitinib monotherapy in rheumatoid arthritis.
The study was sponsored by Pfizer. Dr. Mease’s financial disclosures included Pfizer as well as a long list of companies that make conventional and biologic disease-modifying antirheumatic drugs. Another four authors disclosed financial ties to Pfizer and other pharmaceutical companies. Five coauthors were employees of Pfizer.
WASHINGTON – Tofacitinib demonstrated efficacy comparable to adalimumab in patients with active psoriatic arthritis (PsA) and an inadequate response to conventional disease-modifying antirheumatic drugs in the phase III OPAL Broaden study.
“This is the first study to demonstrate efficacy of a JAK [Janus kinase] inhibitor in PsA,” said lead author Philip J. Mease, MD, of Swedish Medical Center, Seattle. “The primary endpoints were achieved with tofacitinib [Xeljanz] versus placebo. Onset of efficacy of tofacitinib on the ACR20 [the American College of Rheumatology 20% improvement criteria] was observed as early as week 2. Radiographic non-progression rates were low and similar to placebo. Improvement was seen in enthesitis and dactylitis as well as in joint and skin symptoms, and efficacy was maintained through month 12. Tofacitinib is a potential future option for the treatment of PsA.”
The study enrolled 422 patients with active PsA diagnosed within the last 6 months or longer, and all also had plaque psoriasis at screening. The primary endpoint was ACR20 response at 3 months.
Patients were randomized to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab (Humira) 40 mg subcutaneously every 2 weeks, or placebo. At 3 months, placebo patients were re-randomized to tofacitinib 5 mg or 10 mg twice daily. The trial was completed by 372 patients (88.4%).
At baseline, groups had similar demographic and disease characteristics. Patients had a median age just under 50 years, tended to be overweight, and had disease duration that ranged from 5 to 7 years. The majority of patients had enthesitis and dactylitis, and all were on background disease-modifying antirheumatic drugs.
All of the active treatment arms achieved statistically significant rates versus placebo on the primary endpoint of ACR20 response at 3 months: 50% in the tofacitinib 5-mg group, 61% in the tofacitinib 10-mg group, and 52% in the adalimumab group, compared with 33% of placebo-treated patients. ACR20 responses increased out to 12 months in 68%, 70%, and 60%, respectively in the three active treatment arms. At 3 months, ACR50 responses in the three active treatment arms were 28%, 40%, and 33%, respectively, and for ACR70 were 17%, 14%, and 19%.
Health Assessment Questionnaire Disability Index (HAQ-DI) responses were statistically significant for all three active dosing arms, compared with placebo.
“Placebo patients re-randomized to tofacitinib also had good ACR responses at month 12,” Dr. Mease said.
The rate of radiographic non-progression at month 12 was similar in all treatment arms at about 95%, including former placebo patients who switched to tofacitinib.
Skin responses, according to Psoriasis Area and Severity Index (PASI) 75, were 43% for tofacitinib 5 mg twice daily, 44% for tofacitinib 10 mg twice daily, and 39% for adalimumab. At 12 months, the percentage of patients achieving PASI 75 increased for all three treatment arms.
The same pattern was observed for enthesitis and dactylitis.
Minimal disease activity was seen at 3 months in about 25% of all the active treatment arms, and the rates improved at month 12.
There were few discontinuations due to adverse events in any group. Adverse event rates were similar across all treatment arms at month 3, including the placebo arm. The rate of serious adverse events reported at month 12 was 5% for tofacitinib 5 mg twice daily, 2.9% for tofacitinib 10 mg twice daily, 7.8% for adalimumab, and 6% in placebo patients switched to either dose of tofacitinib at month 3.
Laboratory changes were similar to those reported with tofacitinib monotherapy in rheumatoid arthritis.
The study was sponsored by Pfizer. Dr. Mease’s financial disclosures included Pfizer as well as a long list of companies that make conventional and biologic disease-modifying antirheumatic drugs. Another four authors disclosed financial ties to Pfizer and other pharmaceutical companies. Five coauthors were employees of Pfizer.
WASHINGTON – Tofacitinib demonstrated efficacy comparable to adalimumab in patients with active psoriatic arthritis (PsA) and an inadequate response to conventional disease-modifying antirheumatic drugs in the phase III OPAL Broaden study.
“This is the first study to demonstrate efficacy of a JAK [Janus kinase] inhibitor in PsA,” said lead author Philip J. Mease, MD, of Swedish Medical Center, Seattle. “The primary endpoints were achieved with tofacitinib [Xeljanz] versus placebo. Onset of efficacy of tofacitinib on the ACR20 [the American College of Rheumatology 20% improvement criteria] was observed as early as week 2. Radiographic non-progression rates were low and similar to placebo. Improvement was seen in enthesitis and dactylitis as well as in joint and skin symptoms, and efficacy was maintained through month 12. Tofacitinib is a potential future option for the treatment of PsA.”
The study enrolled 422 patients with active PsA diagnosed within the last 6 months or longer, and all also had plaque psoriasis at screening. The primary endpoint was ACR20 response at 3 months.
Patients were randomized to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab (Humira) 40 mg subcutaneously every 2 weeks, or placebo. At 3 months, placebo patients were re-randomized to tofacitinib 5 mg or 10 mg twice daily. The trial was completed by 372 patients (88.4%).
At baseline, groups had similar demographic and disease characteristics. Patients had a median age just under 50 years, tended to be overweight, and had disease duration that ranged from 5 to 7 years. The majority of patients had enthesitis and dactylitis, and all were on background disease-modifying antirheumatic drugs.
All of the active treatment arms achieved statistically significant rates versus placebo on the primary endpoint of ACR20 response at 3 months: 50% in the tofacitinib 5-mg group, 61% in the tofacitinib 10-mg group, and 52% in the adalimumab group, compared with 33% of placebo-treated patients. ACR20 responses increased out to 12 months in 68%, 70%, and 60%, respectively in the three active treatment arms. At 3 months, ACR50 responses in the three active treatment arms were 28%, 40%, and 33%, respectively, and for ACR70 were 17%, 14%, and 19%.
Health Assessment Questionnaire Disability Index (HAQ-DI) responses were statistically significant for all three active dosing arms, compared with placebo.
“Placebo patients re-randomized to tofacitinib also had good ACR responses at month 12,” Dr. Mease said.
The rate of radiographic non-progression at month 12 was similar in all treatment arms at about 95%, including former placebo patients who switched to tofacitinib.
Skin responses, according to Psoriasis Area and Severity Index (PASI) 75, were 43% for tofacitinib 5 mg twice daily, 44% for tofacitinib 10 mg twice daily, and 39% for adalimumab. At 12 months, the percentage of patients achieving PASI 75 increased for all three treatment arms.
The same pattern was observed for enthesitis and dactylitis.
Minimal disease activity was seen at 3 months in about 25% of all the active treatment arms, and the rates improved at month 12.
There were few discontinuations due to adverse events in any group. Adverse event rates were similar across all treatment arms at month 3, including the placebo arm. The rate of serious adverse events reported at month 12 was 5% for tofacitinib 5 mg twice daily, 2.9% for tofacitinib 10 mg twice daily, 7.8% for adalimumab, and 6% in placebo patients switched to either dose of tofacitinib at month 3.
Laboratory changes were similar to those reported with tofacitinib monotherapy in rheumatoid arthritis.
The study was sponsored by Pfizer. Dr. Mease’s financial disclosures included Pfizer as well as a long list of companies that make conventional and biologic disease-modifying antirheumatic drugs. Another four authors disclosed financial ties to Pfizer and other pharmaceutical companies. Five coauthors were employees of Pfizer.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: ACR20 was achieved at 3 months by 50% in the tofacitinib 5 mg group, 61% in the tofacitinib 10 mg group, and 52% of the adalimumab group versus 33% of placebo patients, and responses persisted out to Month 12.
Data source: OPAL Broaden was a Phase III trial that included 422 patients with active psoriatic arthritis in both joints and skin.
Disclosures: The study was sponsored by Pfizer. Dr. Mease’s financial disclosures included Pfizer as well as a long list of companies that make conventional and biologic disease-modifying antirheumatic drugs. Another four authors disclosed financial ties to Pfizer and other pharmaceutical companies. Five coauthors were employees of Pfizer.
VIDEO: ACR recommendations for glucocorticoid-induced osteoporosis unveiled
WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.
“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.
The draft recommendations build upon the 2010 ACR recommendations.
“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”
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The draft recommendations were developed via GRADE (Grading of Assessment, Development, and Evaluation) methodology by a core team of internists, rheumatologists, a GRADE expert, a voting panel, and an expert panel.
Recommendations for risk assessment
Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.
For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.
“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.
FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.
A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
Treatment
The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.
All patients should take calcium and vitamin D, regardless of risk level.
The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).
“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.
For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.
Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.
Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.
Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.
Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.
The authors and sponsors had no relevant financial disclosures.
WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.
“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.
The draft recommendations build upon the 2010 ACR recommendations.
“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The draft recommendations were developed via GRADE (Grading of Assessment, Development, and Evaluation) methodology by a core team of internists, rheumatologists, a GRADE expert, a voting panel, and an expert panel.
Recommendations for risk assessment
Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.
For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.
“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.
FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.
A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
Treatment
The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.
All patients should take calcium and vitamin D, regardless of risk level.
The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).
“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.
For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.
Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.
Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.
Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.
Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.
The authors and sponsors had no relevant financial disclosures.
WASHINGTON – New American College of Rheumatology recommendations for glucocorticoid-induced osteoporosis prevention and treatment include refinements in risk assessment and treatment.
“These are draft recommendations not yet accepted by ACR,” said Lenore M. Buckley, MD, of Yale University, New Haven, Conn. “They are intended to be dynamic, because risk factors change for patients over time,” she added.
The draft recommendations build upon the 2010 ACR recommendations.
“About 1% of the United States population is on glucocorticoid treatment. Fracture is the most common adverse event, and trabecular bone in the spine is the most vulnerable,” Dr. Buckley explained in her presentation of the recommendations at the annual meeting of the American College of Rheumatology. “The risk of glucocorticoid (GC)-induced fracture is related to dose level and cumulative dose.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The draft recommendations were developed via GRADE (Grading of Assessment, Development, and Evaluation) methodology by a core team of internists, rheumatologists, a GRADE expert, a voting panel, and an expert panel.
Recommendations for risk assessment
Risk assessment for GC-induced osteoporosis is individualized. “You need to know the patient in front of you. Fracture risk is not just related to GC use, but also to bone mass, age, and race. Older age, female gender, Caucasian race all increase risk, and these factors need to be brought in to assessment,” Dr. Buckley explained.
For men and women over age 40, the Fracture Risk Assessment Tool (FRAX), which calculates the 10-year fracture risk in adults over age 40, should be used for risk assessment, incorporating GC use as a risk factor, she said.
“Adjust risk of FRAX according to dose of glucocorticoid. For 2.5-7.5 mg/day, the FRAX risk is fine, but if the patient is on higher doses, adjust the FRAX accordingly,” she said.
FRAX is not valid for women and men under age 40, she continued. A new recommendation is the inclusion of a moderate risk group based on very low bone mass score (Z score less than –3 below the standard deviation of the mean) and/or rapid bone loss (greater than 10% in 1 year). Patients who had prior GC-associated fracture under 40 years are considered high risk.
A thorough history and physical exam are necessary for all patients, and risk assessment should be done within 6 months of GC initiation. Physical exam should be repeated annually, and bone mineral density (BMD) should be assessed every 2-3 years for patients who continue on GC.
Treatment
The proposed treatment recommendations were not age dependent. Patients with moderate to high risk should be treated, in descending order, with oral bisphosphonates, intravenous bisphosphonates, teriparatide (Forteo), and denosumab (Prolia). The order of preference for these treatments was based on cost, efficacy, toxicity, and patient preference.
All patients should take calcium and vitamin D, regardless of risk level.
The proposed recommendations also addressed four special groups considered at significant risk: women of childbearing potential, organ transplant recipients, children, and people on very high doses of GC (greater than 30 mg/day, cumulative dose of 5 g/year).
“For women of childbearing potential, there are emerging data suggesting that bisphosphonates are safe. For this group, consider oral bisphosphonate and teriparatide as a second choice. Animal data suggest that IV bisphosphonates and denosumab are harmful to the fetus,” Dr. Buckley said.
For organ transplant recipients, general recommendations can be followed with two provisions: Kidney transplant recipients should have a work-up for metabolic bone disease, and denosumab should not be used in people on multiple immunosuppressants.
Optimize calcium and vitamin D for children, and treat with oral bisphosphonate, Dr. Buckley continued. If oral bisphosphonates are contraindicated, IV bisphosphonates can be used.
Patients on very high GC dose should be treated with oral bisphosphonates if they are age 30 or older.
Osteoporosis medications can be discontinued in low-risk patients who stop taking GC, but should be continued for those at moderate to high risk.
Patients who benefit from osteoporosis medications but remain at moderate to high risk at the end of 3 years should continue GC treatment.
The authors and sponsors had no relevant financial disclosures.
AT THE ACR ANNUAL MEETING
Abatacept makes inroads in psoriatic arthritis
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
WASHINGTON – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
ASTRAEA (Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Week 24 ACR20 response rates were 39.4% for abatacept vs. 22.3% for placebo (P less than .001).
Data source: International, randomized, double-blind, multicenter phase III study of 424 patients with active psoriatic arthritis.
Disclosures: Bristol-Myers Squibb funded the study. All of the investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.
Urate-lowering therapy poses no harm to kidney function
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
WASHINGTON – Evidence supporting the renal benefits of urate-lowering therapy in patients with hyperuricemia and gout comes from two separate studies presented at the annual meeting of the American College of Rheumatology.
In the first study, allopurinol did not increase the risk of developing chronic kidney disease (CKD) in newly diagnosed patients with gout and normal or near-normal kidney function. The second study found that urate-lowering therapy (ULT) improved kidney function in patients who already had CKD.
Allopurinol in gout
The study was prompted by the recognition that gout patients are underdiagnosed and undertreated, and even when they have a diagnosis, both patients and primary care physicians who treat the majority of gout patients shy away from ULT.
“Further exacerbating the poor management of gout is the common practice of lowering the dose or stopping allopurinol when a patient with gout begins to have a decline in kidney function, which inevitably adds to the poor control of gout,” Dr. Vargas-Santos explained.
The study was based on electronic health records from the Health Improvement Network (THIN) database that includes patients treated by general practitioners in the United Kingdom. The study enrolled 13,608 patients with newly diagnosed gout and normal kidney function who initiated ULT with allopurinol; these patients were compared with 13,608 gout patients (matched by propensity score) in the THIN database who did not start ULT.
Patients were aged 18-89 years (mean age, 58 years) with incident gout diagnosed between 2000 and 2014 who had at least one contact with a general practitioner within a year of study enrollment. The investigators analyzed the relationship between allopurinol use by gout patients and the development of CKD stage 3 or higher.
At a mean follow-up of 4 years, there was no increased risk of developing CKD stage 3 or higher in the allopurinol users: 1,401 of the allopurinol initiators versus 1,319 of nonusers developed CKD stage 3 or higher. The relative risk of developing CKD stage 3 or higher on allopurinol was 1.05, which was not statistically significant. “Our study shows that there was no risk of harm to the kidney with allopurinol. This suggests that if a patient on gout presents with declining kidney function, it is better to look for other causes and keep the patient on allopurinol to lower serum urate. Accumulating evidence supports this. Doctors have to be less fearful of prescribing allopurinol. Gout patients deserve better,” Dr. Vargas-Santos said.
ULT in CKD
ULT improved kidney function in patients with CKD in a large retrospective study, with the greatest improvement observed in patients with CKD stage 3 and some improvement observed in patients with CKD stage 2. ULT had no benefit in patients with CKD stage 4, suggesting that these patients are too advanced to improve.
The study was conducted from 2008 to 2014 and included 12,751 patients with serum urate levels of greater than 7 mg/dL and CKD stages 2, 3, and 4 at the index date (the first time this test result was reported). Patients were drawn from the Kaiser Permanente database and treated by primary care physicians. Patients were followed for 1 year from the index date. The primary outcome measure was a 30% increase or a 30% decrease in glomerular filtration rate (GFR) from baseline to the last available result.
Of the 12,751 patients, 2,690 were on ULT and 10,061 were not. Goal serum urate (sUA) was achieved in 1,118 (42%) of patients on ULT. Among patients who achieved goal sUA, a 30% improvement in GFR was observed in 17.1% versus 10.4% of patients who did not achieve goal sUA, for an absolute difference of 6.7% (P less than .001).
For patients at goal versus those not at goal, the ratio of improvement was 3.4 and 3.8, respectively.
“This study suggests that patients with CKD should be tested for uric acid independent of whether they have gout or not. Getting to goal is important. Stage 3 CKD is the sweet spot where patients got the most pronounced benefit from urate-lowering therapy,” he said. “Stage 4 CDK is too late.”
The authors of both studies had no relevant financial disclosures to report.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The first study found that allopurinol did not increase the risk of developing CKD stage 3 or higher in gout patients with normal or near-normal kidney function. The second study found that reaching goal with urate-lowering therapy led to improved kidney function, especially in patients with stage 3 CKD.
Data source: Two population-based studies based on the U.K.’s THIN database. The first included 13,608 patients and 13,608 matched controls. The second study included 12,751 patients with serum urate levels of greater than 7 mg/dL.
Disclosures: The authors of both studies had no relevant financial disclosures to report.
Tocilizumab makes big impression in giant cell arteritis treatment
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
WASHINGTON – Tocilizumab treatment every week or every other week for 52 weeks with a 26-week prednisone taper was superior to a short and long course of tapered prednisone and also cut the rate of steroid use in half when compared with long-course prednisone in patients with giant cell arteritis in the largest-ever trial of patients with the disease.
The treatment represents a milestone in the treatment of giant cell arteritis (GCA), “a chronic, often devastating, difficult to manage disease,” John Stone, MD, said in his presentation of the results of the randomized, double-blind, placebo-controlled GiACTA trial at the annual meeting of the American College of Rheumatology.
Tocilizumab, an IL-6 receptor-alpha inhibitor, is approved by the Food and Drug Administration for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.
The difficulty in treating GCA is made evident by the fact that “at least 10% of patients with GCA lose their vision, and the long-term morbidity of glucocorticoid treatment – the only treatment thus far for this disease – is substantial,” he said. “For more than 65 years, no true steroid-sparing treatment has been proven effective.”
Remissions rise while flares and steroid use decline
GiACTA enrolled 251 GCA patients over 22 months from 14 countries and 76 sites (61 in Europe and 15 in North America). Median age was 69 years; 74% were female; and 97% were white.
“This trial was 2.5 times as large as any trial conducted in GCA,” Dr. Stone said.
Patients with GCA were eligible for the study if they met modified 1990 ACR classification criteria for GCA as follows: elevated C-reactive protein (CRP) with unequivocal cranial symptoms or unequivocal symptoms of polymyalgia rheumatica; and imaging evidence of large-vessel vasculitis (ultrasound was not permitted).
Patients were randomized to one of four treatment arms: Group 1, prednisone with 6-month taper until week 52 on no other therapy; Group 2, prednisone with 52 weeks of taper; Group 3, weekly tocilizumab injection plus the same steroid taper as Group 1; and Group 4, tocilizumab every other week with same steroid taper as Group 1.
Investigators were blinded to the prednisone taper regimen and the treatment.
Dr. Stone reported 52-week results for the primary endpoint of GiACTA (i.e., sustained remission from week 12 to 52 for tocilizumab versus prednisone 26-week taper). The study is continuing open-label for another year.
The rates of sustained remission at 52 weeks were significantly higher for both weekly tocilizumab (56% of 100 patients; P less than .0001) and every-other-week tocilizumab (53% of 49 patients; P = .0002) versus 14% for short-course prednisone (14% of 50 patients). The rate of sustained remission at 52 weeks was 18% of 51 patients for long-course prednisone.
“The inclusion of CRP did not affect the outcome. After removing CRP from the primary analysis, both endpoints were highly statistically significant for the tocilizumab groups,” Dr. Stone noted.
The same pattern was evident for time to first flare following clinical remission, with the best results in Group 3 and Group 4 – the two tocilizumab groups. The weekly tocilizumab group had a sustained response following the cessation of prednisone, but the every-other-week tocilizumab group had a drop-off after stopping prednisone. More flares were seen in Groups 1 and 2.
Flares were defined as recurrence of GCA signs or symptoms; increased erythrocyte sedimentation rate greater than 30 mm/h attributed to GCA; or two consecutive CRP elevations. Flares were treated by increase in prednisone dose. The cumulative dose of prednisone was cut in half in both tocilizumab arms, compared with the long-course prednisone treatment arm.
“The reduction in prednisone use in patients taking tocilizumab was clinically significant,” Dr. Stone said.
According to the Short-Form 36, a patient-reported outcomes measure, tocilizumab improved global quality of life while quality of life declined in both prednisone taper groups.
There were no new safety signals related to tocilizumab reported during the trial. No cases of vision loss and no deaths occurred. Two malignancies were reported in the prednisone groups.
“Adverse events were not disproportionate in the tocilizumab-treated groups,” Dr. Stone said.
Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: The rate of sustained remission at 52 weeks was 56% with tocilizumab versus 14% for short course prednisone and 18% for long-course prednisone.
Data source: Randomized, double-blind, placebo-controlled trial of 251 patients.
Disclosures: Some of the investigators had financial relationships with Roche, which sponsored the study, or other pharmaceutical companies. Several investigators were employees of Roche or its wholly-owned subsidiary, Genentech.