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In this article, we highlight some of the most important pharma reports presented at ACR 2016 this year.
A phase three, randomized, double-blind trial of 208 patients (105 golimumab, 103 placebo) finds that intravenous golimumab 2mg/kg was efficacious in reducing the signs and symptoms of ankylosing spondylitis as compared with placebo.
At 16 weeks, significantly greater proportions of golimumab patients vs placebo patients had ASAS20 (73.3% vs. 26.2%), ASAS40 (47.6% vs. 8.7%), and BASDAI 50 (41.0% vs. 14.6%) responses (all p<0.001; Table). Reductions in BASFI were also significantly greater with golimumab.
“Safety and Efficacy of Intravenous Golimumab in Adult Patients with Active Ankylosing Spondylitis: Results through Week 28," Atul A. Deodhar. 2016 ACR/ARHP Annual Meeting. Abstract number 1043. Nov. 13, 2016.
Gout patients on receiving both lesinurad and allopurinol for two years continue to meet their sUA target levels in this phase three trial.
Patients received 200 or 400 mg lesinurad combine with allopurinol, achieved target sUA <6.0 mg/dL at 6 and 12 months than with ALLO alone (P<0.0001).
The safety profile of lesinurad and allopurinol was comparable to allopurinol alone.
“Examination of Serum Uric Acid (sUA) Lowering and Safety With Extended Lesinurad + Allopurinol Treatment in Subjects With Gout (CLEAR Extension),” Kenneth G. Saag. 2016 ACR/ARHP Annual Meeting. Abstract number 208. Nov. 13, 2016.
At the approved dose of 200 mg once daily combined with an xanthine oxidase inhibitor, lesinurad demonstrated a consistent safety profile gout. Treatment-emergent adverse event rates comparable to those with xanthine oxidase inhibitor alone.
University of Chicago researchers pooled data to investigate the safety of lesinurad 200 and xanthine oxidase inhibitor and lesinurad 400 with xanthine oxidase inhibitor in three core studies and two extension studies for two years.
Treatment-emergent adverse events were higher for lesinurad 400 than 200 mg and placebo in combination with xanthine oxidase inhibitor. However, there were no new safety concerns in the extension studies.
“Integrated Safety of Lesinurad, A Novel Uric Acid Reabsorption Inhibitor for the Treatment of Gout,” Michael A. Becker. 2016 ACR/ARHP Annual Meeting. Abstract number 207. Nov. 13, 2016.
Lesinurad for gout patients at 200 mg once daily combined with a xanthine oxidase inhibitor demonstrated infrequent rates of renal-related adverse events, except for higher serum creatinine elevations. Most of the serum creatinine elevations in core and extension studies resolved.
Researchers from the University of California, San Diego investigated renal-related safety of lesinurad 200 and xanthine oxidase inhibitor and of lesinurad 400 and xanthine oxidase inhibitor in three core studies and two extension studies for 24 months.
In core studies, the most common treatment-emergent adverse events were blood creatinine increased, blood urea increased, renal failure, and renal impairment, which were consistent in core and extension studies.
“Renal Safety of Lesinurad: A Pooled Analysis of Phase III and Extension Studies,” Robert Terkeltaub. 2016 ACR/ARHP Annual Meeting. Abstract number 206. Nov. 13, 2016.
Two randomized, double-blind, phase three extension studies show that gout patients treated with lesinurad and an xanthine oxidase inhibitor for up to two years exhibited continued increases in the rate of complete resolution of tophi and reduction in tophus area, as well as decreased rates of gout flares.
Researchers from Lariboisiere Hospital evaluated the impact of long-term treatment with either lesinurad 200 and xanthine oxidase inhibitor or lesinurad 400 with xanthine oxidase inhibitor on complete resolution of target tophi and gout flare requiring treatment rates in CLEAR and CRYSTAL extension studies.
Over 24 months, the researchers saw increased rates of complete resolution of tophi, continued reductions in total tophus area and decreased proportions of subjects with gout flares requiring treatment.
“Clinical Response of Tophus and Flares to Extended Use of Lesinurad in Combination With a Xanthine Oxidase Inhibitor in Patients With Gout(CLEAR/CRYSTAL Extension),” Thomas Bardin. 2016 ACR/ARHP Annual Meeting. Abstract number 209. Nov. 13, 2016.
A phase 3 study evaluating subcutaneous abatacept treatment vs. placebo in 424 patients with psoriatic arthritis demonstrated superior efficacy (measured by ACR20 response) at week 24 vs. placebo (95% CI, 17.2 (8.7, 25.6) with p<0.001) and maintained efficacy at one year, regardless of previous treatment with a TNFi. Abatacept had a similar safety profile as placebo.
“Abatacept in the Treatment of Active Psoriatic Arthritis: 24-Week Results from a Phase III Study,” P Mease. 2016 CR/ARHP Annual Meeting. Abstract number 1041. Nov. 13, 2016.
Of 422 randomized psoriatic arthritis patients, 405 (96.0%) completed three months and 373 (88.4%) completed 12 months. Significantly greater improvements in ACR20 response rates and ÎHAQ-DI were observed for both tofacitinib doses vs placebo at three months. These were maintained for one year. Greater improvements were observed for adalimumab vs placebo. Tofacitinib 5 and 10 mg BID demonstrated superiority for ACR20 response rate as early as two weeks (22.4% and 31.7% vs 5.7%; p<0.001).
“Efficacy and Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, or Adalimumab in Patients With Active Psoriatic Arthritis and An Inadequate Response to Conventional Synthetic DMARDs: A Randomized, Placebo controlled, Phase 3 Trial,” Philip Mease, MD. Abstract 2983, Plenary Session III: Discovery 2016, Nov. 15, 2016.
Rheumatoid arthritis patients prescribed tofacitinib, a biologic DMARD or a conventional synthetic DMARD experienced standardized incident rates for infections, cardiovascular disease, malignancies, and gastrointestinal perforation.
This was a five-year interim analysis that evaluated the rates of adverse events in patients just initiating tofacitinib (760) or a biologic (4,628) and conventional synthetic DMARDs (1,328).
“Real World Results from a Post-Approval Safety Surveillance of Tofacitinib (Xeljanz): Over 3 Year Results from an Ongoing US-Based Rheumatoid Arthritis Registry,” Arthur Kavanaugh. 2016 ACR/ARHP Annual Meeting. Abstract 2595. Nov. 15, 2016.
Certolizumab pegol with methotrexate does not appear to be superior to adalimumab with methotrexate, a study presented at the 2016 American College of Rheumatology annual meeting shows.
The study, by University of Texas Southwestern Medical Center in Dallas, also points to the clinical benefit and safety of switching to a second TNF inhibitor.
The data is based on a 104-week randomized trial, investigator-blind trial in which 915 patients were randomized to either combination treatment with certolizumab pegol and methotrexate (n=457) or adalimumab with methotrexate (n=458). Researchers found no statistical differences in either group for treatment emergent adverse events (TEAEs; 75.4% and 73.8%), serious TEAEs (13.0% and 11.1%), and serious infections and infestations (3.3% and 3.1%), by treatment at AE onset (event rate per 100 patient years 257.5 vs 260.0).
"Comparison of Certolizumab Pegol Versus Adalimumab: 2-Year Efficacy and Safety Results from a Superiority, Investigator-Blind, Head-to-Head Study," Roy Fleischmann. 2016 ACR/ARHP Annual Meeting. Abstract number 2987. 11:00 a.m., Nov. 15, 2016.
Rheumatoid arthritis patients who achieve a high level response with tofacitinib may be able to discontinue methotrexate or glucocorticoids and maintain their response.
Overall, 186 of 1,608 patients that received methotrexate at long-term extension baseline (11.6%; tofacitinib 5 mg BID: n=49; tofacitinib 10 mg BID: n=137) discontinued methotrexate and 319/1,434 pts that received glucocorticoids at baseline (22.2%; tofacitinib 5 mg BID: n=114; tofacitinib 10 mg BID: n=205) discontinued glucocorticoids to three years. Baseline demographics and disease characteristics for patients receiving tofacitinib 5 and 10 mg twice daily were generally similar irrespective of whether pts discontinued/continued methotrexate or glucocorticoids. Most patients who discontinued methotrexate or discontinued glucocorticoids achieved CDAI remission (≤2.8) or low disease activity (>2.8–≤10) vs CDAI incomplete response (>10) at Year 3 (Table 1).
“Discontinuation of Methotrexate or Glucocorticoids in Patients with Rheumatoid Arthritis Treated with Tofacitinib: Clinical Efficacy Data from Long-Term Extension Studies,” Roy Fleischman, MD. 2016 ACR/ARHP Annual Meeting. Abstract 1646. Nov. 14, 2016.
Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy in the reduction of active rheumatoid arthritis disease activity and in the improvement in the signs and symptoms and physical function in rheumatoid arthritis patients with intolerance or inadequate response to methotrexate.
The overall incidences of adverse events and serious adverse events were similar between groups, as was the rate of infections and serious infections.
“Efficacy and Safety of Sarilumab Versus Adalimumab in a Phase 3, Randomized, Double-Blind, Monotherapy Study in Patients with Active Rheumatoid Arthritis with Intolerance or Inadequate Response to Methotrexate,” Gerd Burmester. 2016 ACR/ARHP Annual Meeting. Abstract number 3221. Nov. 12, 2016.
Rheumatoid arthritis patients taking once-daily oral baricitinib reported significant improvements in joint pain, severity of morning joint stiffness and tiredness as early as day three as compared to placebo - and within three weeks as compared to adalimumab.
University of Oxford and NYU Langone Medical Center researchers assessed daily diary scores from phase three trial patients with rheumatoid arthritis who recorded symptom severity for 12 weeks.
“Speed of Onset of Effect on Patient-Reported Outcomes Assessed through Daily Electronic Patient Diaries in the Baricitinib Phase 3 RA Clinical Program.” Peter C. Taylor. Alvin F. Wells. 2016 ACR/ARHP Annual meeting, Abstract number 1599. Nov. 14, 2016. /
Two phase three baricitinib studies of elderly patients with rheumatoid arthritis showed this group of patients (249 patients ≥65 years old) experienced significant improvements with baricitinib 4 mg at 12 weeks.
Adverse events occurred more frequently in the elderly population compared to patients aged <65 years; however, the prevalence of serious adverse events and discontinuations due to adverse events was not different from placebo.
“Safety and Efficacy of Baricitinib in Elderly Patients with Moderate to Severe Rheumatoid Arthritis” Roy Fleishmann. 2016 ACR/ARHP Annual meeting, Abstract number 1590. Nov. 14, 2016.
Employment status in patients with rheumatoid arthritis could be directly related to disease prognosis, Bristol-Myers Squibb reported at ACR 2016 in November.
The study of 3,621 patients found that patients in the worst prognostic category were older (median age: 62 vs 58 years), had more established disease (median disease duration: 4 vs 1 years) and greater disease activity as compared with those in the best prognosis category. There was a significant relationship between work and poor prognosis category. Patients in the worst prognosis category were less likely to work at all as compared to those in the best prognosis category. At 12 months, poor prognosis and work status remained statistically significant.
“Work Status in Patients with Rheumatoid Arthritis Who Have Poor Prognostic Factors: Findings from a US Observational Cohort,” E Alemao. 2016 ACR/ARHP Annual Meeting. Abstract number 549. Nov. 13, 2016.