SEMAPHORE: Tocilizumab reduces disease activity in steroid-dependent polymyalgia rheumatica

MidwireThe interleukin-6 receptor inhibitor tocilizumab may significantly reduce disease activity and the amount of prednisone needed in people with active glucocorticoid-dependent polymyalgia rheumatica (PMR), suggesting results from a phase 3 trial published in gamma.

The findings complement previous studies, such as the PMR-SPARE trial that reported that tocilizumab was associated with improved rates of PMR remission in patients with newly-emerged disease.

For the present analysis, Valérie Devochelle-Pinsek (Brest University Hospital, France) and colleagues measured the drug’s efficacy in patients with persistent disease activity, defined as having a PMR activity score, calculated using the C-reactive protein (CRP PMR) level. -AS), more than 10 points despite prednisone dose at or above 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, along with a pre-specified standard taper of oral prednisone.

At 24 weeks, Devauchelle-Pensec and team found that individuals given tocilizumab were 2.3 times more likely than those given placebo to achieve a primary efficacy end point of CRP PMR-AS of less than 10 points combined with a prednisone dose at or below 5 mg/day or a decrease in prednisone dose of at least 10 mg/day from baseline.

In all, 67.3% of patients in the tocilizumab group achieved this result, compared with 31.4% of the placebo group.

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

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

By contrast, 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 disability index in the Health Assessment Questionnaire.

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

Devauchelle-Pensec noted that the study’s exclusion criteria included several health conditions and laboratory test abnormalities, and thus “[f]More research is needed to confirm efficacy and to determine the balance between potential benefits and harms.”

In an accompanying editorial, Brendan Antiokos, MD, of Johns Hopkins, in Baltimore, MD, USA says: “The SEMAPHORE study results support the efficacy of tocilizumab in the management of polymyalgia rheumatica in patients receiving chronic steroid therapy.”

But he emphasizes, “The results do not apply to all patients with PMR, some of whom can be treated with much lower doses of prednisone or completely diluted steroids over a similar time frame.

“These patients may not need treatment with a biologic therapy.”

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