BackgroundGlucocorticoids (GC) are the cornerstone of treatment in Polymyalgia rheumatica (PMR) [1]. However, they are associated with considerable toxicity and inefficacy in part of the patients. Rituximab (RTX) was effective for PMR in a 21-week randomized controlled trial (RCT), however results from longer follow-up is still absent [2].ObjectivesTo assess, in a randomized double blinded fashion, the clinical and GC-sparing effects one year after RTX.MethodsIn the BRIDGE-PMR, an RCT of 38 recently diagnosed and 9 relapsing PMR (2012 EULAR/ACR classification criteria) patients recruited from the Sint Maartenskliniek, patients were randomly allocated in a 1:1 ratio and treated with 1x 1000mg RTX / placebo (PCB) iv, identical pre-medication and an accelerated GC tapering protocol. After the 21-week study, patients were assessed in a double blinded prospective extension study up to one year after infusion. The primary outcome at one year was between group difference in GC-free remission (PMR-activity score < 10). Analysis was performed with Fischer’s exact test and a two-tailed p-value < 0.05 was considered significant. Secondary outcomes were proportion of relapsing patients during the extension, proportion of patients with CRP > 5mg/l during the extension, cumulative GC dose, DMARD use, EQ-5D score, and adverse events (AE).ResultsThe proportion of patients in GC-free remission after one year was significantly higher in the RTX group (48%, 11/23) compared to the PCB group (17%, 4/24), with an absolute difference of 31% (95%-CI 6-56), a relative risk of 2.9 (95%-CI 1.1-7.7), p=0.03. The secondary outcomes showed statistically significant differences in RTX versus PCB in median GC cumulative dose: 1595 versus 2302 mg (p = 0.04) and median PMR-AS: 6 versus 15 (p = 0.02) (Table 1 and Figure 1). No differences were seen in other secondary outcomes.Table 1.Primary and Secondary Outcomes for Rituximab Versus Placebo Treatment One Year After InfusionPlacebo [n=24]Rituximab [n=23]p-valueRemission, number (%)10 (42%)15 (65%)0.15GC-free remission, number (%)4 (17%)11 (48%)0.03Cumulative GC dose 0-52 weeks, in mg2302 (1595 - 2881)1595 (1275 – 2260)0.04Cumulative GC dose 21-52 weeks, in mg959 (91 – 1442)160 (0 - 902)0.10Relapse patient 21-52 weeks, number (%)*14 (58%)12 (52%)0.77PMR-AS**15.25 (7.75 - 22.5)6.3 (4.7 - 12.1)0.02CRP serum level, in mg/L3.5 (2 - 5)3 (1 - 4)0.29physicians’ VAS, 0-102 (0.2 - 3.7)1 (0 - 2)0.08Morning stiffness, in minutes25 (4 - 60)10 (0 - 30)0.06VAS pain, 0-103 (1.45 - 6.4)1.8 (0.7 - 5)0.16EQ5D-5L, score at week 52#0.71 (0.65 – 0.77)0.71 (0.63 – 0.77)0.87EQ5D-5L, change week 21-52#0 (-0.03 - 0.09)0.07 (-0.05 - 0.10)0.56Methotrexate use, number (%)4 (17%)2 (9%)0.67Adverse events, total, % of patients8, 26%6, 33%0.75Notes. * Relapse was defined as therapy intensification, based on either a) an increase in oral prednisolone, b) adding intramuscular methylprednisolone, or c) starting or switching a DMARD due to treatment inefficiency ** Remission is based on the PMR-AS, calculated by CRP +VASp +VASph + (MST *0.1) + EUL, and a PMR-AS < 10 was considered remission or low disease-activity. # Number of patients for placebo versus RTX were n=23 versus n=23 respectively at week 52, and for comparison of change between week 21-52 total number of patients were n=21 versus n=23 respectivelyFigure 1.Cumulative GC Dose 0-52 Weeks, in mgConclusionEfficacy of 1x1000 mg RTX in PMR was maintained up to 1 year follow-up, while also demonstrating a GC sparing effect. A larger trial, also assessing effect of on demand retreatment, is needed to confirm our results, and provide insight in which patients most likely benefit from RTX.