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.

Severe type 2 leprosy reaction with COVID-19 with a favourable outcome despite continued use of corticosteroids and methotrexate and a hypothesis on the possible immunological consequences.

Type 2 leprosy reaction (T2LR), or Erythema Nodosum Leprosum (ENL), often poses a therapeutic challenge to clinicians and commonly requires long courses of steroids for control. While immunosuppressants are known to achieve control and lower steroid dependence in T2LR, the prospect of managing a severe T2LR in conjunction with COVID-19, with the concern of worsening COVID-19 with long-term immunosuppression has not previously been encountered. We report a case of severe T2LR treated with oral steroids and methotrexate, with COVID-19 infection acquired during hospital stay, and a favourable outcome achieved despite the continued use of immunosuppressants. We discuss the possible reasons for this both in terms of the drug pharmacodynamics and the immunological profile of T2LR.

Intramatricial injections for nail psoriasis: An open-label comparative study of triamcinolone, methotrexate, and cyclosporine.

BACKGROUND: One of the most effective options available for treating psoriatic fingernails is intramatricial injection of triamcinolone acetonide. Efficacies of intramatricial methotrexate and cyclosporine have not been comparatively evaluated to date. METHODS: Ninety fingernails in 17 patients were assigned to three groups of thirty nails each, and treated with intramatricial injections of triamcinolone acetonide (10 mg/ml), methotrexate (25 mg/ml) and cyclosporine (50 mg/ml) respectively. Each nail was given two injections with a 6-week interval, and graded at 24 weeks using the Nail Psoriasis Severity Index. RESULTS: In both triamcinolone acetonide and methotrexate groups, 15 (50%) nails out of 30 showed >75% improvement. In the cyclosporine group, only ten (33%) nails showed >75% improvement. Side effects were most in the nails treated with cyclosporine. LIMITATIONS: The limited follow-up period of 24 weeks may have been insufficient for detecting delayed remissions. The number of patients was small and there was no randomization or blinding. The lack of a placebo/ no- treatment arm can be considered a limitation. CONCLUSIONS: Amongst the three drugs studied, intramatricial methotrexate injection yielded the most improvement with minimum side effects, results being comparable to intramatricial triamcinolone acetonide injection. Cyclosporine was the least effective drug, with the most side effects. Intramatricial injection therapy is a safe, economical, simple and effective therapeutic modality in the management of nail psoriasis.

Methotrexate iontophoresis versus coal tar ointment in palmoplantar psoriasis: A pilot study.

BACKGROUND: Palmoplantar psoriasis is often disabling and refractory to conventional therapy. Systemic drugs are indicated in its severe form, but side effects are a concern with their use. Methotrexate is one such systemic drug which is effective and cheap. To reduce systemic toxicity, methotrexate has been tried topically but results have been inconsistent due to poor drug penetration into the skin by passive diffusion. Iontophoresis may enhance its absorption and efficacy. AIM: To evaluate the efficacy and safety of topical methotrexate iontophoresis in comparison with coal tar ointment in the treatment of palmoplantar psoriasis. METHODS: Thirty-one patients with palmar and/or plantar psoriasis were selected for the study and 28 patients completed it. The side having more severe involvement was treated while the other palm/sole served as a control. Iontophoresis using methotrexate solution was carried out on the study palm/sole with the injectable preparation of methotrexate (50 mg/2 ml) once a week for the first 4 weeks and subsequently every two weeks, for a total of six sittings. The control palm/sole was treated with coal tar ointment on other days. Erythema, scaling, induration and fissuring scores were noted in both groups before and after treatment. RESULTS: Both study and control groups showed decreases in scores but the reduction was more in the study group, the difference being statistically significant. LIMITATIONS: Drawbacks of our study include the small sample size and the lack of follow-up. The study and control arms were not exactly matched and the study was not blinded. CONCLUSION: Methotrexate iontophoresis was safe and more effective than coal tar ointmentin palmoplantarpsoriasis.

Management of chronic neuritis with a combination regimen of lower doses prednisolone and methotrexate: a brief report.

INTRODUCTION: Recommended fixed duration prednisolone regimen was not found effective in the treatment of chronic neuritis. Alternate effective treatment was being sought to reduce the deformity in the field of leprosy. OBJECTIVE: We wished to see whether a prolonged course of prednisolone and methotrexate could be of any help for them. METHODOLOGY: In 2012-2014, an open pilot clinical study was undertaken where three chronic neuritic patients were treated with lower doses prednisolone and methotrexate for 12 months and a follow up period was delivered for 12 months. The study was undertaken in one of the outdoor clinics of the university. RESULTS: Complete and permanent remission of neuritis was achieved with appreciable functional recovery. Few mild self-limiting side-effects from prednisolone were observed and there was no side-effects from methotrexate. CONCLUSION: Prolonged course of prednisolone and methotrexate was found safe and effective in treating chronic neuritis.

Relapse in psoriasis with two different tapering regimens of methotrexate: a randomized open-label controlled study.

UNLABELLED: Background : Systemic therapy with methotrexate is a very useful modality in psoriasis, but relapses can occur soon after stopping it. Aim : To compare the relapse rates in psoriasis with two different tapering regimens of methotrexate after control is achieved. Methods : This was a randomized open-label controlled study, and patients of chronic plaque psoriasis with psoriasis area and severity index (PASI) >10 were included. Methotrexate 0.3 mg/kg weekly was given and the PASI calculated every 2 weeks. After achieving a 75% reduction in the PASI (PASI-75), patients were assigned randomly in to one of three groups. In the half-dose group, the dose of methotrexate was reduced to half and given weekly; in the 2-weekly group, the same dose was given at 2-week intervals; in the control group, methotrexate was stopped. Patients were followed up for 12 weeks. Results : Out of 141 registered patients, 81 were included: 27 in the half-dose group, 28 in the 2-weekly group, and 26 in the control group. After further exclusions due to adverse effects and loss to follow-up, the results were analysed for 16, 17 and 19 patients respectively in the 3 groups. There was statistically a highly significant difference in relapse rates between the half-dose and control groups (P < 0.001), and a significant difference between the 2-weekly and control groups (P = 0.001). Relapse rates in the half-dose and 2-weekly groups did not show a significant difference (P = 0.680). LIMITATION: Many (35.8%) patients were excluded and only 52 (64.2%) completed the study. CONCLUSION: There appears to be no significant difference in the frequency of relapse in psoriasis whether methotrexate is tapered by halving the weekly dose or by doubling the interval between two doses, and both methods led to fewer relapses than abrupt cessation of the drug.