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New Kid on the Block for Ankylosing Spondylitis
June 12 2015 12:51 PM ET — via RheumReports
Over the past few years, we have seen multiple new therapies approved for the treatment of plaque psoriasis, psoriatic arthritis and rheumatoid arthritis. Unfortunately, the majority of these therapies have not been effective for ankylosing spondylitis. Thus far, we have not had a biologic alternative to TNF inhibitors in patients with ankylosing spondylitis.
Secukinumab is a fully human monoclonal antibody against interleukin-17A made by Novartis Pharma AG. It was originally intended as a treatment for RA, but that was not further pursued after disappointing Phase 2 studies. Secukinumab has had multiple strong Phase 3 studies for the management of plaque psoriasis, including the ERASURE study (NEJM 2014), where it was found to be superior to etanercept. It was recently approved for the management of plaque psoriasis by Health Canada in March 2015 and Phase 3 data for psoriatic arthritis (FUTURE 1 and 2) looks good. Studies are ongoing in other indications including polymyalgia rheumatica.
At ACR 2014, Novartis presented early results from Phase 3 RCTs, MEASURE 1 and 2, which all met their primary and secondary endpoints. Over the past two days, 52-week data from these studies has been presented at EULAR 2015. As you may recall, MEASURE 1 compared IV secukinumab 10mg/kg at baseline, week 2 and 4, and then either 75mg or 150mg SC every 4 weeks from week 8 versus placebo on the same schedule. MEASURE 2 compared SC secukinumab 75mg or 150mg vs placebo at week 1,2,3, and every 4 weeks starting at week 4. At week 16, placebo-treated patients were re-randomized to secukinumab 150 or 75mg.
Fifty-two week data from MEASURE 1 showed early improvement in clinical symptoms and MRI measures of spinal inflammation, which was sustained to 52 weeks. Maintenance with the higher dose SC was associated with a trend towards better scores. In MEASURE 2, the ASAS20 response rate at week 16 was 61.1% with secukinumab 150mg vs 28.4% with placebo (p=0.0001). Clinical responses to secukinumab 75mg did not reach significance. At week 52, ASAS 20/40 response to secukinumab 150mg was 73.8%/57.4% and was comparable to those originally randomized to placebo who received secukinumab 150mg starting at week 16 (n=34) whose scores were 75%/56.3%. There were also sustained improvements in physical function and health-related quality of life. Among the patients enrolled in MEASURE 2, 62% were TNF-naïve, while 38% had failed one previous TNFi. ASAS20 scores were slightly lower, but still statistically significant for TNF-IRs compared to TNF-naïve subjects. Overall, there were no major safety signals identified and the most common serious adverse event was serious infection.
Secukinumab seems like it is going to be a promising new player for the management of ankylosing spondylitis (and probably psoriatic arthritis). Just when and how we will use it in clinical practice remains to be seen. In the meantime, I guess we have to go back to our basic science books to re-learn all about interleukin-17 and what it does.
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About the Author
Dr. Shahin Jamal
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.
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