Background The recently published EULAR treatment guideline recommended treatment for DMARD naïve patients is Methotrexate (MTX) with(out) glucocorticoids (GCs). Combination therapy with classical DMARDs however is not recommended, because well proven evidence of superior efficacy is suggested to be lacking. Furthermore possible drug toxicities might influence the physician’s choice of induction therapy.
Objectives To compare the 3 month clinical efficacy of: (1) combination DMARD vs. MTX mono-therapy and (2) oral GCs bridging therapy vs. 1 dose of intramuscular (im) GCs in patients with early RA.
Methods For this study data are used of a currently ongoing single-blinded randomized clinical trial in patients ≥18 years with recent-onset arthritis (tREACH). We included patients who had a high probability (>70%) according to their likelihood of progressing to persistent arthritis based of the prediction model of Visser. The Visser algorithm and 2010 criteria for RA have similar discriminative abilities to identify patients at risk of persistent arthritis at 1 year. Patients were randomized into 3 induction therapy strategies: (A) Combination therapy (MTX 25 mg/wk + SASP 2 gr./day + HCQ 400 mg/day) with GCs im (Depomedrol 120mg), (B) Combination therapy with an oral GCs tapering scheme (starting dose 15 mg) and (C) MTX with oral GCs similar to B. In case of “treatment failure”, defined as DAS>2.4, medication is intensified to MTX with a biological. Disease activity, functional ability, and adverse events were assessed.
Results A total of 281 patients were randomly assigned to [A] (n=91), [B] (n=93) or [C] (n=97). Disease activity, after 3 months, was 0.39 (0.67–0.11, 95% CI) lower in patients with initial combination therapy compared to MTX mono-therapy. Difference in disease activity between the different GCs bridging therapies was 0.03 (–0.24–0.31, 95% CI). After three months 50% less biologicals were prescribed in the combination therapy groups. Functional ability (respectively 0.53 (0.40–0.66) [A] vs 0.53 (0.40–0.65) [B] vs 0.69 (0.55–0.84) [C]) and medication adjustments due to adverse events (resp. 22% [A] vs 20% [B] vs 16% [C]) did not differ between groups.
Conclusions In patients with >70% chance of developing a RA a combination of DMARDs is superior to MTX mono-therapy in achieving low disease activity after three months, unbiased for GCs. Consequently 50% less biologicals were prescribed in the combination therapy groups. Furthermore intramuscular and oral GCs are equally effective as bridging therapy and can both be used.
Funding Unrestricted grant from Pfizer bv. [0881-102217]
Disclosure of Interest None Declared
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