Background Recent progress in the understanding of rheumatoid arthritis (RA) pathogenesis leads to growing interest in the concept of pre-RA, a clinical stage in which very early intervention could be more efficacious.
Objectives To assess the efficacy of very early therapeutic interventions in pre-RA patients, i.e., with either undifferentiated arthritis, or ACPA-positive arthralgia/arthritis (ie, very early RA, VERA), through a systematic literature review (SLR) and meta-analysis (MA).
Methods The SLR was performed following Cochrane guidelines. The search used “undifferentiated arthritis” or “very early rheumatoid arthritis” (VERA) associated with “therapy” or “treatment”, and was limited to randomized controlled trials (RCTs) published in English over the last five years. It was conducted in Pubmed, Embase and Cochrane RCT databases, as well as EULAR and ACR congress abstracts of the last two years. Two independent readers (SH, BH) extracted the following data through a standardized form: study quality, patient status at baseline (either undifferentiated arthritis or VERA), the type of intervention, and disease characteristics over time as well as occurrence of RA.
The main outcomes that were analysed for the meta-analysis were RA occurrence at 52 weeks and beyond and the absence of radiographic progression at week 52. The meta-analysis was performed using RevMan with Mantel-Haenszel method.
Results The search identified 595 abstracts, of which 9 RCTs were finally selected (including 2 congress abstracts). Eight were related to undifferentiated arthritis; 1 to VERA. The studies included 1156 patients, weighted mean age 45.8+/-15.2 years, mean symptoms duration 16.2+/-12.6 weeks; 66.0+/-17.7% were female.
The occurrence of RA at week 52 or more was available in 7 studies (assessing 800 patients). Early therapeutic intervention – either methylprednisolone (80 to 120mg IM), methotrexate, TNF-blocker, abatacept or rituximab -reduced the risk of occurrence of RA with a pooled odds ratio (OR) of 0.72 (95% CI [0.54; 0.96]), p 0.02 (Figure).
There was no statistically significant difference between the treatments or placebo, for the absence of radiographic progression (pooled OR 1.36 [0.82;2.27])
The outcome was assessed at Week 52 for all studies, except for Van Dongen 2007 (PROMPT), where it was assessed at Week 120. MethylPDN, methylprednisolone; MTX, methotrexate.
Conclusions This meta-analysis demonstrates that early therapeutic intervention significantly reduces the risk of RA onset in pre-RA patients. The benefit /risk balance and feasibility in clinical practice remain to be further assessed.
Disclosure of Interest None declared