ARE BIOLOGIC AND TARGETED SYNTHETIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS ASSOCIATED WITH WORK PARTICIPATION IMPROVEMENT IN EARLY RHEUMATOID ARTHRITIS? A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: In early RA, the benefit of treatment with b-/tsDMARDs on work participation (WP), a top-three social role in RA, has seldom been studied. Objectives: To review the effect of treatment with b-/tsDMARDs on employment status (ES), presenteeism and sick leave (SL), in patients with early RA. Methods: A systematic literature review (SLR) was conducted in key electronic databases up to October 2021, to include RCTs assessing the effect of treatment with b-/tsDMARDs vs any comparator on ES, presenteeism and SL in patients with RA (≤ 3y). Two reviewers independently identified eligible studies and extracted data. Random-effects meta-analysis was only performed if ≥3 studies were conducted in comparable populations, assessing WP outcome similarly. Statistical heterogeneity was assessed with I . Results: From 7129 records (65 full-text articles screened), 11 RCTs were included in the SLR (7 in csDMARD naïve patients; 2 in inadequate responder to csDMARDs; 1 bDMARD tapering after initial combination with MTX, and 1 strategy study). Large heterogeneity was found across WP outcomes, measurement instruments, interventions and comparators ( Table 1 ), which together with insufficient data reporting hampered meta-analysis of most outcomes. For ES, to allow meta-analysis, all outcomes were converted to employment loss, for which individual study Odds ratios (OR) were computed. The pooled OR of 4 studies with 779 patients treated with adalimumab, infliximab or baricitinib ( Figure 1 ) showed a lower likelihood of employment loss at weeks 56 to 104 in those treated with MTX+b/tsDMARDs compared to MTX+PBO (OR: 0.65; 95% CI:0.43-0.99). For presenteeism and SL, 33/40 (83%) between-group comparisons showed improvement in favour of b-/tsDMARDs, but an effect size was reported or possible to compute for only 12 comparisons, of which 8 (67%) were statistically significant. Table 1. Overview of between-group results Author, year Study name Intervention (I) Comparator (C) AssessedOutcome Instrument Follow-up(weeks) Favours intervention(+ yes; - no) csDMARD naïve Smolen 2006ASPIRE IFX+MTX ES SCMI 54 + PBO+MTX SL + Bejarano 2008 ADA+MTX ES Weekly diaries 56 + PBO+MTX SL + Anis 2009COMET ETN+MTX SL SCMI 52 + MTX van den Hout 2009BeSt I: IFX+MTX SL SCSI 104 56w: + I vs C 1/2 C1: seq. monotherapy Pres VAS (0-100) 104w: + I vs C 1 | + I vs C2: step-up comb. Therapy + IFX C 3 C3: initial comb. Therapy + IFX van Vollenhoven 2010PREMIER I 1 : ADA+MTX ES SCMI 104 + I 1 vs C | + I 2 vs C I 2 : ADA+PBO Pres + I 1 vs C | + I 2 vs C C: PBO+MTX SL + I 1 vs C | + I 2 vs C Emery 2016OPTIMAPROWD ADA+MTX ES WPAI-RA 24-26 OPTIMA & PROWD + PBO+MTX Pres OPTIMA + SL OPTIMA - Wiland 2016PRIZE I: ETN25/MTX Pres WPAI-RA 117 39W & 65 W: + I vs C 1/2 39W & 65 W: + I vs C 1/2 C 1 : PBO+MTX SL C 2 : PBO+PBO Schiff 2017RA-BEGIN¶ I 1 : BARI+MTX Pres WPAI-RA 52 24w: + I 1/2 vs C I 2 : BARI+PBO SL 52w: + I 2 vs C C: PBO+MTX 24w: + I 1/2 vs C 52w: + I 2 vs C Strand 2021SELECT-EARLY¶ I 1 : UPA 30 Overall work impairment WPAI-RA 12 + I 1/2 vs C I 2 : UPA 15 C: MTX csDMARD Inadequate responders Eriksson 2015Swefot IFX + MTX SL Registry 7 y + csDMARD + MTX Fleischmann 2016AMPLE¶ ABA+MTX Pres WPAI-RA 104 24, 56 & 104w: + ADA+MTX SL 24 & 104w: + SCMI – self composed multiple items; SCSI – self composed single item; WPAI – Work Productivity Activity Impairment questionnaire; p  ≤ 0.05 p  ≤ 0.001 vs C; non-validated instrument; when > 1 I/C or time-point, between-group comparisons and time-points are presented if I vs C differences were observed; ¶ insufficient data reporting to compute effect sizes. Conclusion: A protective effect against employment loss was observed in patients with early RA treated with MTX+b-/tsDMARDs compared to MTX monotherapy. The methodological heterogeneity and insufficient reporting hampers clear conclusions regarding the beneficial effects of b-/tsDMARDs on presenteeism and SL. Efforts to uniformize future studies with WP as outcome by following recently developed points to consider are crucial . REFERENCES: [1]Boonen A, et al. Ann Rheum Dis. 2021; 80:1116-1123. Disclosure of Interests: Mary Lucy Marques: None declared, Alessia Alunno: None declared, Louise Falzon: None declared, Annelies Boonen Speakers bureau: Abbvie /Galapagos, Consultant of: Galapagos, Grant/research support from: Abbvie, Sofia Ramiro: None declared. Citation: , volume 81, supplement 1, year 2022, page 522Session: Rheumatoid arthritis - prognosis, predictors and outcome (POSTERS only)