Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial

Abstract

BackgroundPolymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed.MethodsIn this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks.The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated.ResultsFrom 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721–842) mg and 935 (861–1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient.ConclusionIn patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose.Trial registration numberNCT03263715

Genetically proxied IL-6 receptor inhibition and risk of polymyalgia rheumatica

“…We provide genetic evidence to support IL-6Ri as a therapeutic target for reducing PMR risk. These findings support results of the recent PMR-SPARE trial, in which 19 patients with new-onset PMR who were randomised to tocilizumab demonstrated superior rates of glucocorticoid-free remission, compared with 17 given placebo 5. The current results additionally provide insights into the therapeutic potential of IL-6Ri as monotherapy.…”

Is Tocilizumab Effective and Safe in Polymyalgia Rheumatica and Giant-Cell Arteritis With Polymyalgia Rheumatica?

“…Three studies were excluded because we did not find data on the statistical significance or the studies did not pass the quality appraisal evaluation. Therefore, we included eight articles in this review [4,[11][12][13][14][15][16][17]. The PRISMA flowchart is illustrated in Figure 1.…”

“…Four studies applied GC concomitantly with TCZ (GC combination) [11,12,14,15], and three used TCZ as monotherapy [11,14,15]. In addition, Akiyama et al evaluated monotherapy and GC combinations [4], as represented in Table 4.…”

“…In PMR patients, Akiyama et al reported that two studies showed a >50% reduction of the cumulative GC dose [4]. Bonelli et al reported a decrease in median cumulative prednisone dose in the TCZ group compared to the placebo group (PBO) at 16 weeks, and it was maintained at 24 weeks (781 mg vs. 1,290 mg) [11]. Izumi et al evaluated the prednisolone discontinuation rates.…”

Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica

“…Recently, IL-6 receptor blocking therapy has shown positive results as GC sparing therapy in GCA ( 10 ). Promising results with this therapy have also been reported in PMR ( 11 , 12 ). However, tocilizumab monotherapy is not recommended for these diseases and combination treatment with GC is still imperative, especially in GCA.…”