Fibromyalgia, psoriatic arthritis, SLE, RA: New treatment options presented at ACR
Focus on Rheumatology
Efficacy and safety of various treatment regimens for rheumatologic disorders such as fibromyalgia, psoriatic arthritis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) were a key focus of the American College of Rheumatology (ACR) Annual Meeting.
Following is a brief review of the 10 most frequently viewed abstracts from the 2014 ACR meeting that was held November 15–19 in Boston. For more information on presentations covering a variety of rheumatology topics, visit ACR’s website.
Fibromyalgia: New combination
Results of a Phase IIa study suggested that a combination of celecoxib and famciclovir is efficacious in the treatment of fibromyalgia.
The development of fibromyalgia symptoms can be triggered by numerous stressors such as infections. Researchers theorized that these stressors could be triggering a reactivation of latent herpes viruses and that this reactivation could in turn lead to the central nervous system dysregulation seen in patients with fibromyalgia. They conducted a Phase IIa, 16-week, randomized, double-blind, placebo-controlled study of 143 patients to assess the efficacy and safety of a combination regimen that targets herpes viruses (i.e., famciclovir plus celecoxib) for managing symptoms in patients with fibromyalgia.
The trial included 143 patients. Results showed that patients treated with famciclovir plus celecoxib had a significant decrease in pain from baseline compared with those given placebo. For the 24-hour recall pain numeric rating scale, the absolute change was −1.9 units for active therapy versus −1.1 for placebo (P = 0.031), and for the Fibromyalgia Impact Questionnaire, the change was −2.2 versus −0.92, respectively (P = 0.001). In addition, the investigators noted that safety was not an issue, as more gastrointestinal and nervous system events were observed in the placebo group.
Secukinumab: Safety, efficacy
Three abstracts focused on data with secukinumab (Cosentyx—Novartis), an interleukin-17A antagonist recently approved by FDA for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (see page 37 for more information). At ACR, investigators presented efficacy and safety results from three Phase III trials that evaluated the use of secukinumab for the management of psoriatic arthritis and ankylosing spondylitis.
Psoriatic arthritis. Two studies, FUTURE 1 and 2, which assessed different dosing regimens of secukinumab, both demonstrated improvements in the signs and symptoms of psoriatic arthritis with this new agent.
In FUTURE 1, 606 adult patients with moderate to severe psoriatic arthritis were randomized to placebo or one of two secukinumab treatment arms: 10 mg/kg I.V. every 2 weeks for the first 4 weeks followed by monthly 75-mg subcutaneous injections, or 10 mg/kg I.V. every 2 weeks for the first 4 weeks followed by 150-mg subcutaneous monthly injections. Patients treated with secukinumab had significantly less progression than those receiving placebo from baseline to week 24, as demonstrated by changes in the modified total Sharp scores (0.02 for 75 mg, 0.13 for 150 mg vs. 0.57 placebo), erosion scores (0.08 for 75 mg, 0.04 for 150 mg vs. 0.35 placebo), and joint space narrowing scores (−0.06 for 75 mg, 0.10 for 150 mg vs. 0.23 placebo).
These results were consistent across patients who received prior therapy with a tumor necrosis factor (TNF) inhibitor, were on secukinumab monotherapy, or were receiving concomitant methotrexate. Treatment with secukinumab also resulted in sustained inhibition of joint structural damage through week 52. In addition, patients in the placebo group who switched to secukinumab therapy at week 16 or week 24 had less progression once on active therapy.
In FUTURE 2, 397 adult patients with psoriatic arthritis were randomized to placebo or one of three secukinumab treatment arms: 300 mg, 150 mg, or 75 mg, all administered subcutaneously at baseline and at weeks 1, 2, 3, 4, and every 4 weeks thereafter for 24 weeks. An assessment of the primary endpoint, which was an ACR20 response at week 16, revealed that more patients on active therapy achieved this response than those on placebo (29.3% for 75 mg, 51.0% for 150 mg, 54% for 300 mg vs. 15.3% for placebo).
These positive effects were observed in patients who were TNF-naive and those who had an inadequate response or were intolerant to TNF inhibitor therapy in the past. The greatest efficacy across endpoints was observed with the 300-mg dose. A similar percentage of patients reported adverse events among the two groups (53.8% secukinumab vs. 58.2% placebo).
Ankylosing spondylitis. Results of the MEASURE trial demonstrated that use of secukinumab in patients with ankylosing spondylitis resulted in rapid and significant improvements in the signs and symptoms of the disease, regardless of prior TNF inhibitor therapy.
In MEASURE, 371 adult patients with ankylosing spondylitis were randomized to placebo or one of two secukinumab treatment arms: 10 mg/kg I.V. at baseline and every 2 weeks for the first 4 weeks followed by monthly 75-mg subcutaneous injections, or 10 mg/kg I.V. at baseline and every 2 weeks for the first 4 weeks followed by 150-mg subcutaneous monthly injections.
An assessment of the primary endpoint, which was an ACR20 response at week 16, revealed that more patients on active therapy achieved this response than those on placebo (59.7% for 75 mg, 60.8% for 150 mg, 54% for 300 mg vs. 28.7% for placebo). The results were consistent regardless of prior TNF inhibitor exposure, and the drug was well tolerated, with a similar percentage of patients reporting adverse events across the three groups.
Investigational agent for SLE
Data from a Phase IIb study of sifalimumab, an investigational anti-interferon (IFN)-alpha monoclonal antibody being developed by MedImmune, in patients with moderate to severe SLE suggested that this novel agent is effective at reducing disease severity with an acceptable safety profile.
A total of 431 adult patients with moderate to severe SLE (mean age 39.4 y, 92.3% female, 58.7% Caucasian) despite standard of care treatment were randomized (1:1:1:1) to monthly I.V. sifalimumab 200 mg, 600 mg, 1,200 mg, or placebo for 1 year. A greater percentage of patients in the sifalimumab groups achieved the primary endpoint of SLE Responder Index (4) at day 365 compared with patients on placebo (58.3% for 200 mg, 56.5% for 600 mg, and 59.8% for 1,200 mg vs. 45.4% for placebo).
In addition, significant improvements in joint counts and numerical improvements were seen in FACIT-Fatigue scores when comparing the sifalimumab and placebo groups. A total of six deaths occurred, four in the sifalimumab groups and two in the placebo group. Rates of the most commonly reported adverse events and serious adverse events were similar among the two groups. The investigators did note, however, that herpes zoster occurred more frequently in the sifalimumab groups (3.7% to 8.4%) compared with placebo (0.9%).
Appropriate treatment selection in RA
Five of the most frequently viewed abstracts discussed the management of RA, with a focus on retention rates of subsequent therapies in patients for whom initial nonbiologic or biologic therapies had failed, factors associated with biologic discontinuation, long-term efficacy of tocilizumab (Actemra—Genentech), and efficacy of an infliximab biosimilar.
A review of registry data suggested that use of tocilizumab, an interleukin-6 inhibitor, in patients whose one previous TNF inhibitor agent had failed could be a better option than cycling to a second anti-TNF drug. Data from 259 patients in the Canadian Rhumadata database were assessed to determine the retention rate of tocilizumab compared with adalimumab (Humira—Abbvie), etanercept (Enbrel—Amgen), and infliximab (Remicade—Janssen) in patients with RA whose first anti-TNF agent had failed.
The investigators reported that the 4-year retention rates of these agents were tocilizumab (44.3%), adalimumab (27.2%), etanercept (37.1%), and infliximab (34.0%) when used as second-line biologic agents.
Which biologic to select first?
Another analysis using data from the Canadian Rhumadata database suggested that 5-year retention rates of various biologics are similar among patients who use these agents for the first time after failure of methotrexate therapy. Based on data from 340 patients who received one of these agents as their initial biologic, 5-year retention rates were noted to be 64% for abatacept (Orencia—Bristol Myers-Squibb), 40% for adalimumab, 49% for etanercept, and 42% for infliximab (P = 0.29).
Factors associated with biologic discontinuation.
A third analysis using data from the Canadian Rhumadata database found that factors associated with biologic treatment discontinuation included the type of work and income level of patients, with part-time workers and higher-income patients more likely to stop therapy. In addition, the number of disease-modifying antirheumatic drugs used and the use of methotrexate were associated with a reduced risk of biologic discontinuation.
Longer-term data for tocilizumab.
Two-year data from patients with early RA who were methotrexate-naive and received tocilizumab 8 mg/kg every 4 weeks as monotherapy or in combination with methotrexate showed that this agent resulted in sustained improvement in disease activity and maintained joint damage inhibition. In addition, for patients originally receiving methotrexate monotherapy or tocilizumab 4 mg/kg every 4 weeks plus methotrexate who switched to the 8 mg/kg dose at week 52, further improvements in efficacy were observed at 2 years.
Efficacy of a biosimilar.
Results at 54 weeks for BOW015, a biosimilar of infliximab, in patients with RA on stable methotrexate doses showed this agent to be both safe and effective, with durable efficacy and similar immunogenicity to the reference infliximab product. The ACR20 response at 16 weeks was similar between the BOW015 and reference infliximab groups (89.8% and 86.4%, respectively), and no major differences in the adverse event profiles were observed among the agents.
In addition, a similar percentage of patients initially treated with BOW015 or reference infliximab developed antidrug antibodies at week 58 (approximately 55% in each group).