Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Autor:	Devauchelle-Pensec V; Rheumatology Department, Brest University Hospital, Brest, France.; INSERM 1227, Brest University, Brest, France., Carvajal-Alegria G; Rheumatology Department, Brest University Hospital, Brest, France.; INSERM 1227, Brest University, Brest, France., Dernis E; Rheumatology Department, Community Hospital, Le Mans, France., Richez C; Rheumatology Department, Bordeaux University Hospital and Bordeaux University, Bordeaux, France., Truchetet ME; Rheumatology Department, Bordeaux University Hospital and Bordeaux University, Bordeaux, France., Wendling D; Rheumatology Department, Besançon Regional University Hospital and Bourgogne Franche-Comté University, Besançon, France., Toussirot E; INSERM CIC-1431 Clinical Investigations Center, Besançon University Hospital Besançon, France., Perdriger A; Rennes 1 University, School of Medicine, South Hospital, Rheumatology Department, Rennes, France., Gottenberg JE; Department of Rheumatology, Strasbourg University Hospitals, Strasbourg, France., Felten R; Department of Rheumatology, Strasbourg University Hospitals, Strasbourg, France., Fautrel BJ; Sorbonne Université - Assistance Publique Hôpitaux de Paris, Pitié Salpêtrière Hospital, Rheumatology Department, Paris, France., Chiche L; Internal Medicine Department, European Hospital, Marseille, France., Hilliquin P; Department of Rheumatology, Centre Hospitalier Sud-Francilien, Corbeil-Essonnes, France., Le Henaff C; Rheumatology Department, Hospital, Morlaix, France., Dervieux B; Internal Medicine Department, Hospital, Mulhouse, France., Direz G; Rheumatology Department, Community Hospital, Le Mans, France., Chary-Valckenaere I; Department of Rheumatology, Nancy University Hospital, Nancy, France., Cornec D; Rheumatology Department, Brest University Hospital, Brest, France.; INSERM 1227, Brest University, Brest, France., Guellec D; Clinical Investigations Centre (CIC) 1412, National Health and Medical Research Institute (INSERM), Brest, France., Marhadour T; Rheumatology Department, Brest University Hospital, Brest, France., Nowak E; Public Agency for Clinical Research and Innovation (DRCI), Brest University Hospital, Brest, France., Saraux A; Rheumatology Department, Brest University Hospital, Brest, France.; INSERM 1227, Brest University, Brest, France.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2022 Sep 20; Vol. 328 (11), pp. 1053-1062.
DOI:	10.1001/jama.2022.15459
Abstrakt:	Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu