ACR CONVERGENCE 2021—A randomized efficacy and safety study showed that tocilizumab is superior to placebo for attaining sustained glucocorticoid-free remission in patients with new-onset polymyalgia rheumatica (PMR) receiving background glucocorticoid treatment. Michael Bonelli, MD, associate professor of medicine in the Division of Rheumatology at the Medical University of Vienna, Austria, presented these data during ACR Convergence 2021, held Nov. 3–9.1
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PMR is a musculoskeletal disorder with an unknown cause. Its main symptoms are muscle pain and stiffness. Other symptoms include fever, weakness and weight loss. Genetics and/or environmental factors may be involved in its development. In some cases, PMR develops overnight, but it can also have a more gradual onset. Symptoms are usually worse in the morning and can develop quickly. The disease occurs more commonly in women than men, as well as in people of Scandinavian or Northern European heritage, and almost always in patients older than 50 years of age. The average age of symptom onset is 70 years.2,3
PMR is often misdiagnosed. It does not cause swollen joints, so it can be difficult to recognize. It occurs in approximately 50% of patients diagnosed with giant cell artertis.
PMR rapidly responds to low doses of glucocorticoids, but may recur as the dose is tapered. Continued glucocorticoid treatment may lead to significant adverse effects. A need exists for effective, steroid-sparing agents to treat PMR.
Dr. Bonelli and colleagues performed this randomized, double-blind, multi-center, phase 2/3 study in patients with new-onset PMR from three Austrian centers. In the study, patients received either 162 mg of subcutaneous tocilizumab or matching placebo in a 1:1 ratio weekly for 16 weeks. Additionally, all patients received a starting dose of 20 mg of prednisone accompanied by a rapid taper schedule over 11 weeks.
The primary end point was the proportion of patients in glucocorticoid-free remission at week 16. After week 16, follow-up was obtained up to week 24 to assess sustained efficacy and safety (NCT03263715 PMR-SPARE).4 Secondary end points included time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24.
Results: Thirty-six patients were randomly assigned to receive either tocilizumab (n=19) or placebo (n=17). At week 16, glucocorticoid-free remission was achieved by 12 (63.2%) of the patients treated with tocilizumab compared with two (11.8%) of the patients who received placebo. This finding corresponds to an odds ratio of 12.9 (95 % confidence interval [CI], 2.2 to 73.6) in favor of tocilizumab (P=0.002 by Fisher’s exact test).
The mean time to first relapse in days (± standard deviation [SD]) for patients who received tocilizumab was 130±13 days compared with patients who received placebo, 82 ± 11 days (P=0.007). At week 16, the median cumulative prednisone dose (interquartile range) was 727 mg (range: 721–842 mg) for patients treated with tocilizumab and 935 mg (861–1244 mg) for patients who received placebo (P=0.003). At week 24, the glucocorticoid-free remission rates were similar to those at week 16: 57.9% for patients treated with tocilizumab compared with 17.6% of patients on placebo.
Statistical significance was reached for many secondary outcomes, including cumulative prednisone dose at week 24. The cumulative prednisone dose was 781 mg (range: 721–972 mg) for patients treated with tocilizumab and 1,290 mg (1,106–1,809 mg) for patients who received placebo (P=0.001).
Five patients in the placebo group had a serious adverse event, and one serious adverse event occurred in a patient who received tocilizumab. The specifics of these adverse events were not reported.
This study showed that tocilizumab was superior to placebo for sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose. These results show that tocilizumab may be a viable agent for these patients, improving efficacy and safety in managing PMR.
Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Bonelli M, Radner H, Smolen J, et al. Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE)—A phase 2/3 randomized controlled trial [abstract: 0507]. Arthritis Rheumatol. 2021 Oct;73(suppl 10).
- Polymyalgia rheumatica. Mayo Clinic. 2021
- Diseases and conditions: Polymyalgia rheumatica. American College of Rheumatology. 2019 Mar.
- Aletaha D. A study to evaluate the efficacy of tocilizumab as a remission-induction and glucocorticoid-sparing regimen in subjects with new-onset polymyalgia rheumatica (PMR-SPARE). ClinicalTrials.gov. 2021 Jan 22.