A phase 3 randomized controlled trial has demonstrated that sarilumab, the first FDA-approved biologic for polymyalgia rheumatica, delivers clinically meaningful improvements in health-related quality of life for patients with relapsing disease inadequately managed with glucocorticoid monotherapy. The findings, published in The Lancet Rheumatology, provide strong evidence supporting the IL-6 receptor blocker's role in addressing the significant quality of life impairments experienced by patients with this inflammatory condition.
Trial Design and Patient Population
The double-blind, randomized controlled trial was conducted across 60 centers in 17 countries, enrolling 118 patients aged 50 years or older between October 2018 and July 2020. Participants had a mean age of 68.9 years, with 69% being female and 83% White. All patients had experienced at least one disease flare during glucocorticoid tapering within the previous 12 weeks and had a history of at least 8 weeks of glucocorticoid treatment at 10 mg per day or prednisone dose equivalent.
Patients were randomly assigned 1:1 to receive either subcutaneous sarilumab 200 mg every two weeks with a 14-week glucocorticoid taper (n=60) or placebo with a 52-week glucocorticoid taper (n=58). Patient-reported outcomes were assessed up to week 52 using validated instruments including the SF-36, EQ-5D, HAQ-DI, Pain VAS, and FACIT-F.
Significant Quality of Life Improvements
At week 52, patients in the sarilumab group demonstrated significantly greater improvements than those in the placebo group across multiple quality of life measures. The SF-36 Physical Component Summary showed improvement of 7.65 versus 2.87 (p=0.020), while the Mental Component Summary improved by 3.04 versus -1.71 (p=0.030). Sarilumab also showed favorable results in five of the eight SF-36 domains.
Additional improvements favoring sarilumab included the EQ-5D utility index (0.11 vs -0.02, p=0.034), HAQ-DI (-0.39 vs -0.15, p=0.054), FACIT-F (7.91 vs 4.17, p=0.060), and Pain VAS (-20.57 vs -12.04, p=0.20). Notably, more than half of the sarilumab-treated patients reached normative values in several SF-36 domains, an outcome not observed in the placebo group.
A greater proportion of patients on sarilumab versus placebo reported improvements of minimum clinically important difference or greater SF-36 PCS scores (odds ratio 3.46; 95% confidence interval 1.16 to 10.62; p=0.020). At baseline, 73% of participants assigned to sarilumab and 74% assigned to placebo reported moderate-to-severe fatigue.
Addressing Unmet Medical Need
Glucocorticoids have long been the cornerstone of treatment for polymyalgia rheumatica, with moderate doses of 15-20 mg of prednisone effectively controlling symptoms. However, more than half of patients are unable to taper off therapy successfully, leading to prolonged use and the risk of glucocorticoid-related adverse effects.
Interleukin-6 has been implicated in the pathogenesis of polymyalgia rheumatica, with elevated circulating levels and increased tissue expression observed in affected individuals. Sarilumab, a fully human monoclonal antibody, targets the IL-6 receptor α and effectively inhibits IL-6 signaling. The drug binds with high affinity to both monomeric and dimeric forms of IL-6Rα—approximately 20 times more strongly than tocilizumab, a humanized IL-6R antibody.
Clinical Implications
The investigators noted that "improvements were highest in patients with most severe disease," indicating that sarilumab may be particularly beneficial for those with more challenging cases. The findings provide strong evidence supporting the use of sarilumab in patients whose disease activity and quality of life remain inadequately managed with glucocorticoid monotherapy.
Sarilumab has demonstrated a favorable immunogenicity profile, with a low incidence and low titres of anti-drug antibodies. Importantly, the presence of these antibodies does not appear to impact the safety or efficacy of sarilumab, regardless of concurrent disease-modifying antirheumatic drug use.
The study's lead investigator, Vibeke Strand from Stanford University's division of immunology/rheumatology, concluded that "the use of sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper led to clinically important improvements in health-related quality of life and patient-reported outcomes versus placebo with a 52-week glucocorticoid taper."
