BACKGROUND: Polymyalgia rheumatica is a common inflammatory disease characterized by pain and stiffness in the shoulders and hips. Glucocorticoids are the first-line treatment, but relapses and glucocorticoid-related toxic effects are common, which underscores the need for effective alternatives. Secukinumab is a fully human monoclonal antibody that selectively inhibits interleukin-17A.

METHODS: We enrolled patients with recently relapsed polymyalgia rheumatica and randomly assigned them, in a 1:1:1 ratio, to receive secukinumab at a dose of 300 mg (SEC-300 group), secukinumab at a dose of 150 mg (SEC-150 group), or placebo for 52 weeks. Patients in all the groups also received prednisone on a tapering schedule for 24 weeks. The primary outcome was sustained remission at week 52, defined as remission (the absence of signs or symptoms attributable to polymyalgia rheumatica and no new diagnosis of giant-cell arteritis that warranted escape or rescue treatment) that was sustained from week 12 until week 52. The annual cumulative glucocorticoid dose was a secondary outcome. Safety was also assessed.

RESULTS: A total of 381 patients underwent randomization, and 127 were assigned to each group. At 52 weeks, sustained remission was observed in 41.2% (95% confidence interval [CI], 32.8 to 49.7) of the patients in the SEC-300 group, in 40.6% (95% CI, 32.2 to 49.0) of those in the SEC-150 group, and in 20.4% (95% CI, 13.6 to 27.2) of those in the placebo group (P<0.001 for the comparison of each secukinumab dose with placebo). The mean adjusted annual cumulative glucocorticoid dose was 1603.7 mg in the SEC-300 group, 1683.2 mg in the SEC-150 group, and 2093.0 mg in the placebo group. Serious adverse events occurred in 13.5% of the patients in the SEC-300 group, in 15.9% in the SEC-150 group, and in 14.2% in the placebo group. Nasopharyngitis, hypersensitivity reactions, urinary tract infections, fungal infections, and back pain were more common in the secukinumab groups than in the placebo group.

CONCLUSIONS: Among patients with relapsed polymyalgia rheumatica, treatment with secukinumab plus a 24-week glucocorticoid taper resulted in a higher percentage of patients with remission and in lower cumulative glucocorticoid doses than a glucocorticoid taper alone. (Funded by Novartis; REPLENISH ClinicalTrials.gov number, NCT05767034.).

Family Medicine (FM)/General Practice (GP) rater

Sustained remission remains the treatment target for polymyalgia rheumatica because relapses impair physical function. In this trial, secukin­umab not only resulted in sustained remission over 1 year but was also associated with better scores for fatigue and physical function compared with glucocorticoid treatment alone, a finding that reinforces the clinical relevance of targeting interleukin-17A–mediated pathways in polymyalgia rheumatica. Considering this, to what extent does the concomitant use of glucocorticoids allow for this type of interpretation exclusively attributed to secukinumab?

Internal Medicine rater

This may be a revolutionary change in treating PMR, but the cost is prohibitive at this time ($2000 per 150 mg dose in Canada).

Rheumatology rater

It's interesting to note the IL17 pathway has efficacy in relapsing PMR with similar efficacy between 150mg and 300mg dosing. It's nice to have another option but the cost is an issue and secukinumab's phase 3 trial for GCA was negative. Most would probably start with tocilizumab if they had to escalate to a biologic.