Secukinumab Improves PROs in Psoriatic Arthritis

Secukinumab, Treatment with the monoclonal antibody secukinumab not only improves responses among psoriatic arthritis (PsA) patients, but also results in clinically meaningful improvements in global disease activity, pain, generic and disease-specific measures of health-related quality of life and fatigue, according to a new study. Secukinumab, a high-affinity, fully human monoclonal IgG1κ antibody that selectively binds and neutralizes interleukin-17A, has proven effective in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. “It is equally important to assess patient-reported outcomes (PROs) when evaluating new therapies for PsA,” says Vibeke Strand, M.D., of Stanford University, who added that “the impact of PsA with and without psoriasis is different from RA.” Psoriatic arthritis is known to reduce physical and psychosocial health-related quality of life (HRQoL) of patients. Patient-reported outcomes are important in psoriatic arthritis since the functional effect of the disease and its therapy is based on the patient’s own perception of improvements in the physical signs and symptoms of the disease. “Clinical responses are associated with improvements in PROs, both generic and disease-specific,” Dr. Strand says. In the FUTURE 1 double-blind, phase 3 trial, 606 patients with psoriatic arthritis were randomly assigned to receive intravenous secukinumab at a dose of 10 mg per kilogram at baseline and weeks 2 and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains. The previously reported results show the ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50%) and 75 mg (50.5%) than in those receiving placebo (17.3%). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. These improvements were sustained through 52 weeks. The researchers concluded that “secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group.” They noted that the study was not large enough or long enough to evaluate uncommon serious adverse events or the risks associated with long-term use of secukinumab. In afurther examination of the FUTURE 1 data, Strand and colleagues found that treatment with secukinumab for 24 weeks also resulted in clinically meaningful improvements compared with placebo across multiple PROs. Reported improvements were sustained or further improved through 52 weeks of secukinumab therapy, and the 150 mg dose of secukinumab resulted in consistently better PRO improvements than the 75 mg dose, indicating a dose–response, they state.  [[{"type":"media","view_mode":"media_crop","fid":"51099","attributes":{"alt":"©JPC-PROD/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_7161634106313","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6286","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©JPC-PROD/Shutterstock.com","typeof":"foaf:Image"}}]] It is important to have a medication that improves psoriatic arthritis patients' HRQoL and their ability to perform daily activities, she says. Studies show the impact of psoriatic arthritis on HRQoL and ability to perform daily activities results in a considerable loss of work in the household and on the job. “Therapies that improve HRQoL have the potential to reduce the broad burden of psoriatic arthritis and also reduce its impact on work productivity,” Dr. Strand says. She adds that “based on data at baseline, it is clear that psoriatic arthritis affects all domains of HRQoL, not just the physical domains, such as physical function and pain, as well as fatigue.” Both doses of secukinumab led to clinically meaningful improvements in Short Form-36 (SF-36) Health Survey physical component, mental component summary and all domain scores at week 24, indicating improvements in social and emotional well-being, as well as physical domains. The researchers note that, compared to psoriasis patients, psoriatic arthritis patients generally have lower scores in the physical domains of SF-36 and report largest improvement with treatment in these domains. Among the psoriatic arthritis patients, they did find improvements in the physical and mental domains of SF-36 with secukinumab treatment. The next step in the research, says Dr. Strand, is “to continue to examine the importance of a generic measure of HRQoL, for example, SF-36, with other disease-specific measures, such as PsA Quality of Life and PsA Impact of Disease.”   

References:

Vibeke Strand, Philip Mease, et al. "Secukinumab improves patient-reported outcomes in subjects with active psoriatic arthritis: results from a randomised phase III trial (FUTURE 1)," Annals of the Rheumatic Diseases. DOI:10.1136/annrheumdis-2015-209055

Philip J. Mease, M.D., Iain B. McInnes, Ph.D., et al. "Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis," New England Journal of Medicine. October 1, 2015 DOI: 10.1056/NEJMoa1412679.

Osterhaus JT, Purcaru O. et al. “Discriminant validity, responsiveness and reliability of the arthritis-specific Work Productivity Survey assessing workplace and household productivity within and outside the home in patients with axial spondyloarthritis, including nonradiographic axial spondyloarthritis and ankylosing spondylitis,” Arthritis Research and Therapy. 2014 Aug 6;16(4):R164. DOI: 10.1186/ar4680.