[Accepted Manuscript] Randomized Controlled Trial of Rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjogren's Syndrome.

: We investigated whether rituximab, an anti-B-cell therapy, improved symptoms of fatigue and oral dryness in patients with Primary Sjogren's Syndrome (PSS). : Multicentre, randomised, double-blind, parallel-group placebo-controlled trial, including Health Economic Analysis. Anti-Ro positive patients with PSS, symptomatic fatigue and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally-randomised to either placebo IV or rituximab IV (1000mg in 250mL) at weeks 0, 2, 24 and 26, with pre-and post-infusion medication including corticosteroids. Primary endpoint was the proportion of patients achieving 30% reduction in either fatigue or oral dryness at 48 weeks, measured by Visual Analogue Scale. Other outcomes included salivary and lachrymal flow rates, quality of life, ESSDAI and ESSPRI, symptoms of ocular and overall dryness, pain, global disease assessment and cost-effectiveness. ISRCTN 65360827 Results: All patients (n=133) randomised to placebo (n=66) and to rituximab (n=67) were included in the primary analysis. Among complete cases, 21/56 placebo and 24/61 rituximab patients achieved primary endpoint. After multiple imputation of missing outcomes, placebo and rituximab response rates were 36·8% and 39·8%, respectively (adjusted odds ratio 1·13 95% CI 0·50-2·55). There were no significant improvements in any outcome measure, except unstimulated salivary flow. Mean (SD) costs for rituximab and placebo were £10,752 (SD 264·75) and £2,672 (SD 241·71). There were slightly more adverse events reported in total for rituximab, but no difference in serious adverse events (ten in each group). : Rituximab is neither clinically or cost-effective in this patient population. This article is protected by copyright. All rights reserved.