SEMAPHORE: Tocilizumab Reduces Disease Activity in Steroid-Dependent Polymyalgia Rheumatica

SEMAPHORE: Tocilizumab Reduces Disease Activity in Steroid-Dependent Polymyalgia Rheumatica

medwireNews: The interleukin-6 receptor blocker tocilizumab may significantly reduce disease activity and the amount of prednisone needed in people with active glucocorticoid-dependent polymyalgia rheumatica (PMR), study results suggest a phase 3 trial published in JAMA.

The results complement previous studies, such as the PMR-SPARE trial which reported that tocilizumab was associated with improved PMR remission rates in patients with new-onset disease.

For the current analysis, Valérie Devauchelle-Pensec (University Hospital of Brest, France) and colleagues measured the efficacy of the drug in patients with persistent disease activity, defined as having a PMR activity score, calculated using the level of C-reactive protein (CRP PMR -AS), greater than 10 points despite a dose of prednisone equal to or greater than 10 mg/day.

Study participants were randomly assigned to receive intravenous tocilizumab 8 mg/kg (n=49) or placebo (n=51) every 4 weeks for 24 weeks, in combination with a predefined standardized reduction in oral prednisone.

At 24 weeks, Devauchelle-Pensec and his team found that people who received tocilizumab were significantly 2.3 times more likely than those who received placebo to have achieved the primary efficacy endpoint of a CRP PMR-AS less than 10 points associated with a dose of prednisone equal to or less than 5 points. mg/day or a decrease in prednisone dose of at least 10 mg/day from baseline.

In total, 67.3% of patients in the tocilizumab group achieved this result, compared to 31.4% of those in the placebo group.

Use of tocilizumab was also associated with significantly better outcomes than placebo on a number of secondary endpoints at 24 weeks, including mean CRP PMR-AS score (7.5 versus 14.9 points) , the proportion of patients with a PMR-AS CRP of less than 10 (73.5 versus 43.1%) and the proportion no longer receiving prednisone (49.0 versus 19.6%).

The mean prednisone dose at week 24 was significantly lower with tocilizumab than with placebo (3.8 vs. 6.1 mg/day), while the proportion of patients with a glucocorticoid dose below 5 mg /d or a decrease of at least 10 mg/d vs baseline was significantly higher (75.5 vs 51.1%).

On the other hand, there was no significant difference between the two arms in the number of patients in remission (CRP PMR-AS ≤ 1.5) at 24 weeks, nor in the scores of the physical and mental components of the SF-36 or the Health Assessment Questionnaire Disability Index.

Adverse events (AEs) occurred in 86% of the tocilizumab group and 82% of the placebo group, with infections being the most frequently reported (47 versus 39%).

Devauchelle-Pensec and note that the study exclusion criteria included several health conditions and laboratory test abnormalities, and therefore “[f]Further research is needed to confirm effectiveness and determine the balance between potential benefits and harms.

In an accompanying editorial, Brendan Antiochos, of Johns Hopkins, Baltimore, Maryland, USA, states: “Results from the SEMAPHORE study confirm the efficacy of tocilizumab in the management of polymyalgia rheumatica in patients receiving chronic corticosteroid therapy.

But he points out that “the results do not apply to all patients with PPR, some of whom can be treated with much lower doses of prednisone or reduced steroids entirely over a similar period.

“These patients might not require treatment with biological therapy.”

medwireNews is an independent medical information service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA 2022; 328: 1053–1062
JAMA 2022; 328: 1047–1048

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