Polymyalgia rheumatic
CLINICAL SCIENCE Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial Michael Bonelli , 1 Helga Radner, 1 Andreas Kerschbaumer , 1 Daniel Mrak , 1 Martina Durechova, 1 Jutta Stieger, 2 Rusmir Husic, 3 Peter Mandl , 1 Josef S Smolen, 1 Christian Dejaco , 3,4 Daniel Aletaha 1
ABSTRACT Background Polymyalgia 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. Methods In 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. Results From 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. Conclusion In 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 number NCT03263715 INTRODUCTION Polymyalgia rheumatica is the second most common inflammatory rheumatic disease in the elderly after rheumatoid arthritis, with a peak incidence around 70 years of age. 1 It is clinically characterised by neck, bilateral shoulder and hip girdle pain as well as by morning stiffness which severely impairs patients’ daily activities. 2 Polymyalgia rheumatica is thought to be caused by a systemic inflammatory response that is mainly driven by interleukin(IL)-6. Inflammatory markers, such as C-reactive protein
Handling editor David S Pisetsky
Key messages
► Additional supplemental material is published online only. To view, please visit the journal online (http://dx.doi. org/1 0.1136/a nnrheumdis- 2021-2 21126). 1 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria 2 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria 3 Department of Rheumatology, Medical University of Graz, Graz, Austria Correspondence to Professor Daniel Aletaha, Division of Rheumatology, Medical University of Vienna, Vienna, Austria; d aniel.aletaha@m eduniwien.ac. at Received 15 July 2021 Accepted 24 November 2021 Published Online First 24 February 2022 4 Rheumatology, Brunico Hospital, Brunico, Italy
(CRP) and erythrocyte sedimentation rate (ESR), are almost invariably markedly elevated in these patients. 3 Treatment of polymyalgia rheumatica is primarily based on glucocorticoids at intermediate doses, which are recommended for at least 12 months. 4 Treatment duration with glucocorticoids in clinical practice, however, is often much longer and may even be life-long. 5 6 There is usually a rapid initial response to glucocorticoids, but relapses occur in 50% of patients during tapering. 7 Long-term use of glucocorticoids is associated with adverse What does this study add? ⇒ The results from this PMR-SPARE trial show a high clinical efficacy of tocilizumab compared with placebo for the treatment of new onset polymyalgia rheumatica. ⇒ The evidence provided adds a major therapeutic option to a disease where to date no therapies are approved for sparing glucocorticoids. How might this impact on clinical practice or future developments? ⇒ The results of this trial provide scientific evidence of superiority of tocilizumab compared with placebo for treatment of polymyalgia rheumatica. ⇒ The data provided may serve as basis for future approval of tocilizumab for the indication of polymyalgia rheumatica and facilitate its reimbursement in this patient group. What is already known about this subject? ⇒ Treatment of polymyalgia rheumatica is primarily based on glucocorticoids, which are recommended for at least 12 months, but may extend to several years, in some cases even being life-long, leading to glucocorticoid-related adverse events in up to 65% of the cases. ⇒ Small and uncontrolled studies investigating tocilizumab, an inhibitor of the interleukin-6 receptor, were indicative of its high clinical potential, but randomised controlled trials testing the clinical efficacy of tocilizumab are not available.
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To cite: Bonelli M, Radner H, Kerschbaumer A, commercial re-use. See rights and permissions. Published by BMJ.
et al . Ann Rheum Dis 2022; 81 :838–844.
Bonelli M, et al . Ann Rheum Dis 2022; 81 :838–844. doi:10.1136/annrheumdis-2021-221126
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