Efficacy of methotrexate as add on therapy to H1 antihistamine in difficult to treat chronic urticaria: A systematic review and meta-analysis of randomized clinical trials.

A systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate efficacy of add on methotrexate in chronic urticaria. "PubMed" and "Google Scholar" were systematically searched to identify randomized clinical trials with methotrexate in patients with chronic urticaria not responding to second generation antihistamines. Odds ratios and 95% confidence interval were calculated for estimation of efficacy. Heterogeneity among studies was tested using Tau squared (τ2 ) and I2 . Two RCTs (n = 104) were included. For primary outcome that is, complete remission at 18 weeks in Leducq et al study and patients achieving more than two third reduction in wheal score that is, one of the primary outcomes in Sharma et al study there was no significant difference in methotrexate vs placebo (OR [95%CI] 1.64[0.34, 7.90]). There was no significant difference for complete remission at 18 weeks in Leducq et al study and patients achieving more than two third reduction in the pruritus score (one of the primary outcomes in Sharma et al study) (OR [95%CI] 1.03 [0.24, 4.38]) too. In both studies, methotrexate was well tolerated. There was no significant benefit of add on methotrexate to antihistamine in the treatment of difficult to treat urticaria. Inclusion of only two randomized controlled trials is the limitation of this meta-analysis.