1106: Effect of Tocilizumab on Disease Activity in Patients with Active Polymyalgia Rheumatica on Glucocorticoid Therapy: A Randomized Clinical Trial

Valerie Devauchelle¹, Guillermo CARVAJAL ALEGRIA², Emmanuelle Dernis³, Christophe Richez⁴, Marie Truchetet⁵, Daniel Wendling⁶, ERIC TOUSSIROT⁷, aleth Perdriger⁸, jacques-eric gottenberg⁹, Renaud FELTEN¹⁰, Bruno Fautrel¹¹, laurent chiche¹², Pascal HILLIQUIN¹³, Catherine Le Henaff¹⁴, Benjamin Dervieux¹⁵, Guillaume Direz¹⁶, Isabelle Chary-Valckenaere¹⁷, Divi CORNEC¹⁸, Dewi Guellec¹⁹, Thierry MARHADOUR²⁰, Emmanule Nowak¹⁹ and Alain Saraux²¹, ¹Université de Bretagne Occidentale, Brest, France, ²CHRU de Tours, Tours, France, ³LE MANS general hospital, LE MANS, France, ⁴Université de Bordeaux, Bordeaux, France, ⁵Bordeaux University Hospital, Bordeaux, France, ⁶CHU, University Teaching Hospital, Besançon, France, ⁷CHU de Besançon, Besançon, France, ⁸Rennes University, Rennes, France, ⁹Strasbourg University Hospital, Strasbourg, France, ¹⁰Hôpitaux Universitaires de Strasbourg, Strasbourg, France, ¹¹Sorbonne University Paris, France and Pierre Louis Institute of Epidemiology and Public Health, Paris, France, Paris, France, ¹²hopital europeen, Marseille, France, ¹³Centre Hospitalier Sud-Francilien, Corbeil-Essonnes, France, ¹⁴Morlaix Hospital, Morlaix, France, ¹⁵Mulhouse Hospital, Mulhouse, France, ¹⁶Le Mans Hospital, Le Mans, France, ¹⁷Nancy University Hospital, Vandoeuvre, France, ¹⁸CHRU Brest, Brest, France, ¹⁹Brest University Hospital, Brest, France, ²⁰CHU Cavale Blanche, Brest, France, ²¹CHU Brest, Brest, France

Background/Purpose: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica (PMR). Interleukin-6 antagonists deserve evaluation in active glucocorticoid-dependent PMR.
Our objective was to compare the efficacy of tocilizumab vs. placebo in patients with glucocorticoid-dependent polymyalgia rheumatica.

Methods: Design, Setting, and Participants. This double-blind parallel-group placebo-controlled randomized clinical trial enrolled 101 patients at 17 hospitals in France from February 2017 to October 2019; last follow-up was in November 2020. Inclusion criteria were persistent disease activity (CRP PMR-AS >10) and prednisone ≥10 mg/day. Tocilizumab was donated by Roche and by Chugai.

Interventions. Patients were randomly assigned to intravenous tocilizumab (8 mg/Kg) (n=51) or placebo (n=50) every 4 weeks for 24 weeks, combined with predefined standardized oral prednisone tapering.

Main Outcomes and Measures. The primary efficacy endpoint was CRP PMR-AS< 10 (Min=0-Max 100 with higher values indicating greater activity, no MCID defined) combined with either prednisone ≤5 mg/day or a ≥10-mg prednisone decrease at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity and proportion of patients who were no longer taking prednisone.

Results: Of the 101 patients randomized (mean age, 67.2 years; 68 [67.3%] females), 100 (99%) received at least one infusion and 100% completed the trial. The primary endpoint was achieved in 67.3% and 31.4% of patients in the tocilizumab and placebo groups, respectively ( adjusted relative risk, 2.3; 95% confidence interval [95%CI]: 1.5 to 3.6; P< 0.001). Of 11 reported secondary endpoints at week 24, seven showed significant differences favoring tocilizumab including mean CRP PMR-AS score (7.5 [95% CI, 5.4 to 9.6] vs. 14.9 [95% CI, 11.4 to 18.4]; adjusted difference, 7.5 with 95%CI 3.8 to 11.2; P< 0.001) and proportion of prednisone-free patients (49.0% vs. 19.6%; adjusted relative risk, 2.5; 95%CI: 1.8 to 3.5; P< 0.001). The most frequent adverse events were infections, experienced by 23 (46.9%) patients in the tocilizumab group and 20 (39.2%) in the placebo group.

Conclusion: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared to a placebo, resulted in a significantly greater proportion of patients achieving a CPR PMR-AS< 10 with reduced prednisone requirements at week 24. However, additional trials are needed to confirm efficacy and to determine the balance of potential benefits and harms.



Disclosures: V. Devauchelle, Pfizer, Novartis, AbbVie/Abbott, Novartis, Bristol-Myers Squibb(BMS), Roche-Chugai, Galapados; G. CARVAJAL ALEGRIA, Roche-Chugai; E. Dernis, AbbVie/Abbott, Amgen, Bristol-Myers Squibb(BMS), Janssen, Nordic Pharma France, Novartis, UCB; C. Richez, AbbVie/Abbott, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb(BMS), Galapados, GlaxoSmithKlein(GSK), Eli Lilly, Novartis, Pfizer; M. Truchetet, AbbVie/Abbott, Pfizer, Eli Lilly, Galapados; D. Wendling, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Merck/MSD, Pfizer, Roche, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Eli Lilly, Sandoz, Galapados, Grunenthal; E. TOUSSIROT, None; a. Perdriger, None; j. gottenberg, AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer; R. FELTEN, Novartis, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Janssen, Eli Lilly, Nordic Pharma, Merck/MSD, MEDAC, Pfizer, Sanofi, UCB; B. Fautrel, Pfizer, Novartis, Roche, Sanofi-Aventis, SOBI, UCB; l. chiche, Novartis, Bristol-Myers Squibb(BMS); P. HILLIQUIN, None; C. Le Henaff, None; B. Dervieux, None; G. Direz, Novartis, Roche, Sanofi; I. Chary-Valckenaere, None; D. CORNEC, None; D. Guellec, None; T. MARHADOUR, None; E. Nowak, None; A. Saraux, None.