The combination of an anti-TNF alpha and methotrexate may also prevent the development of antibodies to anti TNF alpha. Observational studies indicated that MTX dose-dependently inhibits the development of anti-drug antibodies and could reduce the accelerated clearance of biological agents associated with loss of therapeutic response in inflammatory diseases. Reduced ADA development influence positively clinical response and therefore likely drug maintenance through optimizations of drug pharmacokinetics and serum anti TNF alpha trough concentrations.
In psoriasis, there is no prospective evaluation of the combination MTX-anti TNF alpha to help to maintain long-term efficacy for all anti TNF alpha. Long-term maintenance treatment with the combination of MTX and infliximab was reported in one small retrospective cohort study of psoriasis patients experiencing a loss of response to infliximab (55). In total 23 patients received as a rescue either azathioprine (5 patients) or weekly MTX (18 patients) (7.5 to 15 mg, average 11.66 mg) in combination with infliximab. After a mean follow up of 26.5 months, only 2 patients on MTX combination stopped infliximab for loss of response which is lower compared to the 50% loss of response observed with infliximab monotherapy (55).
The combination of anti TNF alpha and MTX was also retrospectively assessed in observational studies. Most of them suggest that the systematic combination of MTX to biologic since the anti TNF alpha initiation improve survival rate of biologics (21, 24, 29, 30, 31). A retrospective cohort study including 93 patients treated with infliximab for psoriasis showed that concomitant MTX at an average weekly dose of dose of 7.5 to 17.5 mg of MTX enhanced the maintenance of response and prolonged drug survival (by a mean ± SD of 19.5 ± 8.1 months, P = 0.034) (23). In addition, time until first infliximab dose escalation was delayed in patients receiving MTX (by a mean ± SD of 12.0 ± 6.1 months, P =0 .037). In the same study, after 2 years of treatment, 25% of patients without MTX were still under the initial infliximab regimen versus 40% of patients receiving a combination of infliximab with MTX (30).
The ability of MTX to prolong drug survival was also suggested in psoriatic arthritis in several observational studies (26, 27, 52, 56). In a longitudinal observational study, the 1-year retention rate of anti-tumor necrosis factor alpha medications in patients with RA and PsA were 65.4% and 77.3%, respectively with concomitant MTX associated with a better drug survival (52). In this study, the combination with MTX was also associated with a crude 1-year survival of 85% in PsA versus 70% without concomitant MTX, p=0.02 (52). In the Danish biologics registry DANBIO, male sex, CRP level \>10 mg/liter, concomitant methotrexate use, and low patient health visual analog scale score at baseline were associated with longer drug survival in PsA patients (27).
To summarize, there is a need to improve drug survival as well as level of response rates with biologics, especially for psoriasis patients. Low doses methotrexate when combining to biologics could be an option in psoriasis patients to solve such crucial issues.
