medwireNews: The interleukin-6 receptor inhibitor tocilizumab may significantly reduce disease activity and the amount of prednisone needed in people with glucocorticoid-dependent active polymyalgia rheumatica (PMR), suggest results from a phase 3 trial published in JAMA.
The findings complement previous studies, such as the PMR-SPARE trial which reported that tocilizumab was associated with improved PMR remission rates in patients with recent-onset disease.
For the current analysis, Valérie Devauchelle-Pensec (Brest University Hospital, France) and colleagues measured the efficacy of the medication in patients with persistent disease activity, defined as having a PMR activity score, computed using the C-reactive protein level (CRP PMR-AS), of greater than 10 points despite a 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, combined with predefined standardized tapering of oral prednisone.
At 24 weeks, Devauchelle-Pensec and team found that individuals given tocilizumab were a significant 2.3 times more likely than those given placebo to have achieved the primary efficacy endpoint of a CRP PMR-AS below 10 points combined with either 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 outcome compared with 31.4% of those in the placebo group.
Tocilizumab use was also associated with significantly better outcomes than placebo in a number of secondary endpoints at 24 weeks including mean CRP PMR-AS score (7.5 vs 14.9 points), the proportion of patients with a CRP PMR-AS less than 10 (73.5 vs 43.1%), and the proportion no longer receiving prednisone (49.0 vs 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 dosage 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 physical and mental component scores 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 most commonly reported (47 vs 39%).
Devauchelle-Pensec and note that exclusion criteria for the study included several health conditions and laboratory test abnormalities, and therefore “[f]urther research is needed to confirm efficacy and to determine the balance of potential benefits and harms.”
In an accompanying editorial, Brendan Antiochos, from Johns Hopkins, in Baltimore, Maryland, USA says: “The results of the SEMAPHORE study support the efficacy of tocilizumab in the management of polymyalgia rheumatica for patients receiving chronic steroid therapy.”
But he stresses that the “results do not apply to all patients with PMR, some of whom can be treated with much lower doses of prednisone or tapered off steroids entirely over a similar timeframe.
“These patients might not require treatment with a biologic therapy.”
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