Meta‐Analysis of Treatment for Primary Sjögren's Syndrome

Abstract

ObjectiveThe current focus of treatment in primary Sjögren's syndrome (SS) is symptom management. Since SS is an autoimmune disease with multisystem involvement, systemic immunosuppression may have a role in improving signs and symptoms and preventing progression. We undertook this review to assess the efficacy and safety of immunomodulation on primary SS from randomized clinical trials (RCTs).MethodsFive electronic databases (Medline, Embase, Central, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform) were searched to include RCTs for the treatment of SS. Primary outcome measures included ocular dryness, oral dryness, tear production, and salivary function. Serious adverse events (AEs) and withdrawals due to AEs were also assessed.ResultsThe search yielded 32 trials evaluating 19 different medications. The average duration of diagnosis was long (up to 9.2 years). Twenty‐two trials examined ocular and oral dryness, for which only 2 and 4 trials showed statistically significant improvements, respectively. No studies found a benefit for tear production; few studies found improvements for unstimulated salivary flow (3 of 16 RCTs) and stimulated salivary flow (2 of 14 RCTs). Meta‐analysis at 6 months found improvements as compared to placebo for unstimulated salivary flow (P = 0.003) and a decrease in the erythrocyte sedimentation rate (P = 0.007). No differences were seen for serious AEs, but there were increased withdrawals from AEs (risk ratio 2.33; P = 0.03).ConclusionReducing inflammation potentially improves salivary gland function. No individual immunomodulatory drug demonstrated a consistent benefit in xerostomia and xerophthalmia. Further work is needed to identify SS patients with an ability to improve and with outcomes that are valid and sensitive to change within clinical trials. Tradeoffs in the future between benefit and safety may also be important, because more withdrawals occurred with active treatment.

Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study

“…To date, a small number of randomised controlled trials have examined the effects of different treatments in pSS, with none of these demonstrating convincing clinical efficacy. 23,24 In the double-blind period of Cohort 2 (10 mg/kg IV), a clinically meaningful reduction in This is further suggested by improvements in ESSDAI in Cohort 2 where trough plasma concentrations were above 100 µg/ml, and suggests a dose-response relationship for iscalimab which is in agreement with the dose-dependent pharmacology seen in non-human primates. 16,25 Importantly, iscalimab was well-tolerated and the number of AEs for both cohorts was similar to placebo.…”

EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies

“…This is a small number of studies that is not comparable with rheumatoid arthritis (RA) or with other, more closely-related diseases, such as SLE or systemic vasculitis. Therefore, the evidence accumulated in this century reveals SjS as a true orphan disease from a therapeutic point of view,59 93 with the absence of any efficacious agent, a situation that is in clear contrast with the significant advances achieved in both basic and clinical research during this period. As a consequence of the limited evidence available, therapeutic decisions in daily practice are often based on a mix of reported expert opinions and personal experience, which may vary widely between countries: therefore, the present recommendations are based on the input of experts from 16 European countries and wide international representation from the other continents.…”

Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren’s syndrome

“…In 2014, Devauchelle-Pensec et al 15 randomised 122 primary-2002 patients to receive rituximab (n=63) or PLA (n=57) and found no significant results in the primary outcome (≥30 mm improvement at week 24 on at least 2 out of 4 VAS scores—dryness, fatigue, pain, global, 23% vs 22%, p=0.91), while Bowman et al 19 randomised 133 primary-2002 patients to receive rituximab (n=67) or PLA (n=66) and found no significant results in the primary outcome (reduction ≥30% at week 48 in either fatigue or oral dryness VAS, rituximab 39.3% vs PLA 36.8%, p=0.76). Two recent meta-analyses including the four RCTs have confirmed the lack of significant between-group differences in mean improvements between baseline and week 24 values for fatigue VAS, oral dryness VAS, salivary flow rate and Schirmer test, and no significant difference between groups for the main adverse events 59 60…”