POS0343\u2005RITUXIMAB IS SUPERIOR TO PLACEBO IN POLYMYALGIA RHEUMATICA

Abstract

Corticosteroids remain the cornerstone of polymyalgia rheumatica treatment, but their use has several disadvantages such as long treatment duration and glucocorticoid-related adverse events.1,2 Data on evidence based effective glucocorticoid-sparing agents are negative or absent.2Because B-cells may be involved in the pathogenesis of polymyalgia rheumatica, we evaluated the efficacy of rituximab in polymyalgia rheumatica.In a 21-week double-blind placebo controlled exploratory study, 47 polymyalgia rheumatica patients (recently diagnosed n=38 / relapsing on prednisolone ≥7.5mg/day n=9) fulfilling the 2012 EULAR/ACR criteria, were randomized 1:1 to intravenous rituximab 1 x 1000\u2009mg (n=23) or placebo (n=24), with a 17-week long glucocorticoid co-treatment. Primary outcome was glucocorticoid-free remission at week 21. Secondary outcomes were glucocorticoid ≤5mg/day and adverse events. Several post-hoc analyses were done for robustness of results.Glucocorticoid-free remission was achieved in 48% (rituximab) versus 21% (placebo), one-sided 95%-CI 4% to 100%; p=0.049, and glucocorticoid ≤5mg/day in 100% versus 54% (one sided 95%-CI 20% to 100%; p=0.005). Post-hoc analysis showed efficacy mainly in recently diagnosed patients: glucocorticoid-free remission in 58% versus 21% (one-sided 95%-CI 10% to 100%; p=0.02); glucocorticoid ≤5mg/day in 100% versus 47% (one-sided 95%-CI 29 to 100%; p<0.001). No significant differences were observed regarding other outcomes (Table 1), except for less morning stiffness after rituximab.Table 1.Outcomes at week 21*Rituximab (n=23)Placebo (n=24)Difference, one sided 95%-CIOne sided p-valueCumulative glucocorticoid dose in mg1356 (151)1406 (189)- ∞ to 340.16Median CRP in mg/l (median, IQR) ‡3 (1 to 5)- 1.5 (-9 to 2)2 (1 to 12) [21]-0.16Change from baseline (median, IQR)[22]- 5 (-13 to 0)[21]Mean ESR in mm/hour19 (11) [21]16 (13) [22]- ∞ to 170.79Change from baseline-7 (25) [21]-12 (19) [21]Relapsing patients during follow-up – no (%)†7 (30)8 (33)- 100 to 200.54Morning stiffness in minutes (median, IQR)Change from baseline (median, IQR)5 (0 to 30) -60 (-120 to -5)30 (9 to 90)-20 (-60 to 0)-0.02Rate ratio rituximab versus placebo (95% CI)Any adverse event §1361480.9 (0.8 to ∞)Serious adverse event(s) ††10Infections ‡ ‡17141.2 (0.7 to ∞)Infusion related complaints ¶1033.3 (1.2 to ∞)*Values are means, SD, unless specified otherwise. Numbers of observations is indicated between brackets []. No correction for type I error.† Judged by research physician.‡Wilcoxon rank sum (Mann-Whitney) test§ All adverse events that occurred during the study period were included in the analyses. Adverse events numbers are number of events, not number of patients with events. Safety outcomes were compared by chi-squared test (cumulative incidences). No correction for type I error was performed. All adverse events were graded according to Common Terminology Criteria for Adverse Events version 5.0, grade range 0–5;higher scores indicate worse events.†† was A pulmonary embolism occurred in one patient‡ ‡ Labelled by the research physician. No serious infections ≥ grade 3 occurred.¶ Labelled by research physician. No serious infusion related complaints ≥ grade 3 occurred.CRP denotes C-reactive protein, IQR interquartile range, ESR erythrocyte sedimentation rate, CI confidence intervalRituximab is superior to placebo in combination with 17-week glucocorticoid-treatment to achieve glucocorticoid free remission in polymyalgia rheumatica. The largest effect was seen in recently diagnosed polymyalgia rheumatica patients (funding: Sint Maartenskliniek; Dutch trial number NL7414).[1]González-Gay MA et al. Polymyalgia rheumatica. Lancet 2017;390(10103):1700–12.[2]Dejaco C et al. 2015 recommendations for the management of polymyalgia rheumatica. Ann Rheum Dis. 2015 Oct 1;74(10):1799–807.Figure 1.Mean Polymyalgia Rheumatica Activity Score at each visit.Diane Marsman: None declared, Nathan den Broeder: None declared, Frank van den Hoogen: None declared, Alfons den Broeder Consultant of: Expert witness fee adalimumab biosimilar litigation for Boehringer/Fresenius, Amgen, Merck. Editorial work education for Abbvie,Novartis., Grant/research support from: Research Grants to employer SMK from Abbvie/Sanofi/Pfizer/Novartis or Lilly, Aatke van der Maas: None declared