Background/Purpose:

Co-medication of MTX with TNF inhibitors (TNFi) has proven superior to TNFi monotherapy in improving clinical outcomes in patients with RA. Whether this holds true in psoriatic arthritis (PsA) remains unclear. We undertook this study to summarize the post-hoc data from randomized, controlled trials (RCTs) on PsA to determine the effect of adding MTX to TNFi on joint severity indices and skin scores.

Methods:

We performed a systematic search of PubMed, Medline, Scopus, and the reference lists of relevant articles for studies published up to April 2017. RCTs containing data on the effect of combination MTX and TNFi versus TNFi monotherapy were included. A random effects model was used to pool extracted data. Heterogeneity was evaluated with I²; p-values < 0.05 were considered significant. Relative benefit, the equivalent of relative risk in studies that aim to improve outcomes, was used to measure the effect size of dichotomous variables.

Results:

Eight clinical trials consisting of 1,055 subjects were included. Responses were grouped into categories based on duration of treatment (12±4 weeks, 24±4 weeks, 48±4 weeks) and outcome measured. Meta-analysis was performed when at least two studies provided data for the same outcome during the same time frame. In studies measuring ACR 20/50/70 at Week 12, there was no statistically significant difference between combining TNFi with MTX vs. TNFi alone (Figure 1). The same trend of no added benefit to combination therapy was observed in ACR 20/50/70 at Week 24 and ACR 20 at Week 48. In studies that measured PASI 75, there was a non-significant trend toward increased response at Weeks 24 and 48 with combination therapy compared to TNFi monotherapy (Figure 2).

Conclusion:

In contrast to RA, the post-hoc data gleaned from PsA trials has not suggested a benefit to adding MTX to TNFi in improving joint severity indices. This may be attributed to the fact that MTX monotherapy is generally considered less effective in PsA than in RA. However, the non-significant trend toward increase in PASI 75 suggests that combination therapy may be beneficial in the subset of PsA patients with significant skin involvement. An inherent limitation of the included studies is that subjects in the MTX+TNFi group were already on stable MTX doses prior to initiating TNFi therapy. Thus, studies directly comparing TNFi monotherapy with combination therapy with MTX in MTX-naive patients are needed to arrive at definitive conclusions.

Figure 1. ACR 20/50/70 at Week 12 with adalimumab (ADA) and infliximab (IFX)

Figure 2. PASI 75 at Weeks 24/48 with ADA, etanercept (ETN), and IFX.