Efficacy and Safety of Sarilumab Dose Levels with a 52‑Week Prednisone Taper in Adults with Early Polymyalgia Rheumatica: Randomized Double‑Blind Placebo‑Controlled Trial

The primary objective is to demonstrate the superiority in efficacy of sarilumab 200 mg administered subcutaneously every two weeks combined with a 52‑week prednisone taper compared with a 52‑week prednisone taper alone in participants with early relapsing polymyalgia rheumatica, thereby assessing whether the addition of sarilumab can achieve better disease control while potentially reducing glucocorticoid exposure.

Secondary objectives include:

• To demonstrate superiority in efficacy of sarilumab 200 mg q2w with a 52‑week prednisone taper versus prednisone taper alone in all participants (both newly diagnosed and early relapsing disease).
• To demonstrate superiority in efficacy of sarilumab 150 mg q2w with a 52‑week prednisone taper versus prednisone taper alone in participants with early relapsing disease and in the overall cohort.
• To evaluate safety, immunogenicity, and tolerability of each sarilumab dose level when combined with a 52‑week prednisone taper across all participants.
• To assess the efficacy of each sarilumab dose level with a 52‑week prednisone taper compared with prednisone taper alone in the entire study population.
• To evaluate the effect of sarilumab on participants as measured by patient‑reported outcomes.

The trial enrolled 198 adults diagnosed with polymyalgia rheumatica, a musculoskeletal disease, across both sexes. Participants were required to be older than 50 years and to meet the EULAR/ACR classification criteria. Eligible individuals included those with newly diagnosed disease who had received less than six weeks of corticosteroid therapy, as well as patients with early relapsing disease who had been on prednisone ≥ 10 mg/day for at least eight weeks, experienced a flare within the previous 12 weeks while receiving > 5 mg/day, and were able to commence a standardized 15 mg/day prednisone regimen at randomization. Contraceptive practices had to comply with local regulations. The population comprised generally healthy patients aside from the target condition; no specific dietary, physical‑activity, or habit restrictions were stipulated. Vulnerable status was acknowledged, and enrollment required informed consent consistent with ethical guidelines.

The study is a Phase 5, randomized, double‑blind, placebo‑controlled trial evaluating two dose levels of sarilumab (150 mg and 200 mg administered subcutaneously every two weeks) in adults with early polymyalgia rheumatica who receive a standardized 52‑week prednisone taper starting at 15 mg/day; participants are screened for eligibility, undergo a baseline randomization visit, and then attend study visits approximately every two weeks for drug administration, with additional assessments at weeks 12, 24, 36, and 52, culminating in an end‑of‑study visit; the overall involvement for each participant is up to 52 weeks of treatment plus the screening period; early termination may occur due to serious adverse events, withdrawal of consent, or significant protocol non‑compliance.

The investigational product is sarilumab, supplied as a sterile solution for injection in a pre‑filled syringe. Each dose contains 200 mg of sarilumab, administered subcutaneously every two weeks (q2w) throughout the 52‑week treatment period. The administration is performed by qualified study personnel under aseptic conditions.

The control arm receives a placebo matching sarilumab in appearance and volume, also provided in a pre‑filled syringe for subcutaneous injection every two weeks. The placebo contains no active pharmaceutical ingredient and is administered in the same manner as the active drug to maintain blinding.

All participants receive background therapy with oral prednisone tablets. The prescribed dose is 15 mg daily at study initiation, followed by a standardized taper over 52 weeks. Prednisone tablets are supplied as 5 mg or 1 mg units, taken orally with water.

Dosing schedules are recorded in the study log and verified at each clinic visit. Participants are instructed to maintain a medication diary documenting the date and time of each injection and oral dose. Compliance is assessed by review of the diary, count of returned medication containers, and verification of injection site records. Any missed or delayed doses are documented, and appropriate corrective actions are taken per protocol.

Efficacy will be evaluated using a hierarchy of clinical endpoints. The primary efficacy parameter is sustained remission at Week 52 (yes/no) in participants with early relapsing polymyalgia rheumatica who receive sarilumab 200 mg every two weeks with a 52‑week prednisone taper. Secondary efficacy parameters include sustained remission at Week 52 in all participants (both newly diagnosed and early relapsing), sustained remission at Week 52 in participants receiving sarilumab 150 mg every two weeks with prednisone taper, corticosteroid‑free remission at Week 52, remission at Week 24, time in remission through Week 52, incidence rate of flare through Week 52, and change from baseline in the disease‑specific activity score.

Changes in disease activity will be quantified using the PMR activity score and its component items, assessed at baseline and at Weeks 24 and 52. Health‑related quality of life will be measured with the Short‑Form 36‑item questionnaire version 2 (SF‑36v2), reporting the physical component summary and mental component summary scores at the same time points. All remission and flare assessments are recorded as binary outcomes (yes/no). Data will be collected according to the predefined visit schedule, analyzed using appropriate statistical methods for binary and continuous variables, and reported as proportions, rates, and mean changes from baseline.