Phase 3 Trial of Secukinumab in Polymyalgia Rheumatica
Secukinumab plus prednisone taper improved sustained remission in relapsed polymyalgia rheumatica.
*Phase 3 randomized controlled trial; Level 2 (OCEBM).
Citation
Stone JH, Buttgereit F, Saraux A, et al. Phase 3 Trial of Secukinumab in Polymyalgia Rheumatica. N Engl J Med. 2026;395:637-647. doi:10.1056/NEJMoa2602567
Background
Polymyalgia rheumatica causes shoulder and hip pain and stiffness, mainly in older adults. Prednisone works, but relapse and long-term steroid harms are common, creating a need for steroid-sparing options.
Patients
381 adults age 50 or older with recently relapsed polymyalgia rheumatica during prednisone taper. Excluded: giant-cell arteritis, rheumatoid arthritis, or other inflammatory arthritis.
Intervention
Secukinumab 300 mg or 150 mg injections for 52 weeks plus a 24-week prednisone taper.
Control
Placebo injections plus the same 24-week prednisone taper.
Outcome
Primary: sustained remission at 52 weeks. Secondary outcomes included steroid dose, need for escape or rescue treatment, fatigue (0 to 52; higher is better), and function (0 to 3; higher is worse).
Follow-up Period
52 weeks.
Results
| Outcome | Secukinumab 300 mg | Secukinumab 150 mg | Placebo | Effect vs placebo |
|---|---|---|---|---|
| Sustained remission (primary) | 41.2% (95% CI 32.8 to 49.7) | 40.6% (95% CI 32.2 to 49.0) | 20.4% (95% CI 13.6 to 27.2) | NNT 5 for both doses |
| Complete sustained remission | 28.2% (95% CI 20.3 to 36.0) | 24.5% (95% CI 17.0 to 31.9) | 4.7% (95% CI 1.1 to 8.3) | NNT 5 and 6 |
| Annual prednisone exposure | 1603.7 mg | 1683.2 mg | 2093.0 mg | Mean difference −489.4 mg (95% CI −734.47 to −244.25); −409.9 mg (95% CI −661.8 to −157.9) |
| Escape or rescue treatment | 50.8% | 51.6% | 75.6% | HR 0.5 (95% CI 0.4 to 0.7) for both doses; NNT 5 |
CI = confidence interval; HR = hazard ratio; NNT = number needed to treat.
Efficacy analyses included treated patients; discontinuation or prohibited medicine counted as nonresponse. The control was a standard prednisone taper. Less relapse or rescue treatment appeared to drive the primary benefit. Serious adverse events were similar, but colds, urinary infections, fungal infections, and rash-type reactions were more common with secukinumab.
Limitations
No efficacy data beyond 1 year. Placebo patients discontinued more often, possibly reducing detection of harms. Novartis sponsored design, analysis, and writing support. Results do not apply to patients with giant-cell arteritis or other inflammatory arthritis.
Funding
Novartis funded; sponsor role raises bias concern.
Clinical Application
Consider secukinumab for recently relapsed polymyalgia rheumatica when prednisone toxicity or repeated relapse is a major concern.
Discussion
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In this phase 3 double-blind RCT of relapsed polymyalgia rheumatica, secukinumab plus a 24-week prednisone taper increased sustained remission at 52 weeks versus placebo plus taper (41.2%/40.6% vs 20.4%); is this benefit valid and applicable enough to change practice despite infections, cost, and 1-year follow-up? In the REPLENISH double-blind RCT, sustained remission at 52 weeks occurred in 41.2% of patients receiving secukinumab 300 mg plus prednisone taper versus 20.4% receiving placebo plus taper. Which statement best describes the absolute treatment effect?