Safety and efficacy of methotrexate (0.3 mg/kg/week) versus a combination of methotrexate (0.15 mg/kg/week) with cyclosporine (2.5 mg/kg/day) in chronic plaque psoriasis: A randomised non-blinded controlled trial.

BACKGROUND

Psoriasis is a chronic, inflammatory, relapsing and remitting disease with no cure till date. There is a paucity of trials using a combination of methotrexate (MTX) and cyclosporine (CsA) in chronic plaque psoriasis, due to fear of added toxicity, although they are time tested treatment options for monotherapy.

AIMS

The study aimed to compare the efficacy and adverse effect profile of the standard recommended dose of MTX (i.e. 0.3mg/kg/week) versus a combination of reduced doses of MTX and CsA (i.e. MTX 0.15 mg/kg/week with CsA 2.5mg/kg/day) in patients with chronic plaque psoriasis.

METHODS

Study design was a non-blinded randomised controlled trial. Patients of chronic plaque psoriasis with PASI more than 10 were randomised in 1: 1 allocation to receive either 0.3 mg/kg/week of intramuscular MTX injection or a combination of 0.15 mg/kg/week of intramuscular MTX injection and 2.5 mg/kg/day of CsA rounded off to the nearest 25 mg. Patients were followed up at every 2 weeks for 12 weeks. The doses were kept fixed throughout the study period.

RESULTS

A total of 66 patients received MTX monotherapy, whereas 67 patients received the combination. At baseline, both groups were comparable in their BSA (P = 0.105, Student t-test) and PASI (P = 0.277, Student t-test), which reduced significantly at 12 weeks in both groups (P < 0.001, paired t-test). The achievement of PASI-75 (P = 0.005), PASI-90 (P < 0.001) and PASI-100 (P = 0.001) was more in the combination group (Chi square test). Intention to treat analysis using Chi square test also showed better outcomes for PASI-75 (P = 0.027), PASI-90 (P < 0.001) and PASI-100 (P = 0.001) in the combination group. Combination group also had earlier onset of action (P = 0.001, Chi square test). There was no significant difference between the groups in terms of laboratory and clinical adverse events.

LIMITATIONS

Non-blinded, no comparison with CsA monotherapy arm, no follow up beyond 12 weeks.

CONCLUSION

The combination of reduced doses of MTX and CsA is more efficacious with earlier onset of action and similar adverse effects as with MTX monotherapy.