Combination treatment with methotrexate and cyclosporin for severe recalcitrant psoriasis

Abstract

An increasingly important approach to the management of patients with severe psoriasis is the concurrent use of two systemic treatments. Previous guidelines have advised against the use of methotrexate and cyclosporin in combination. We report the successful use of a combination of methotrexate and cyclosporin in the treatment of 19 patients with severe, recalcitrant psoriasis, 15 of whom had psoriatic arthropathy. Most patients had previously received two or more systemic treatments. Before combination treatment was started nine of the patients were taking methotrexate and 10 were taking cyclosporin at the maximum tolerated doses. The duration of combination treatment was bimodally distributed, with seven patients having short-term treatment (mean +/- SD duration 18. 9 +/- 15.7 weeks) and 12 patients having long-term treatment (mean +/- SD duration 193.2 +/- 160.6 weeks). Those patients who received short-term treatment did not develop any evidence of toxicity from either agent. Of those patients on long-term treatment, three developed mild impairment of renal function that returned to normal following a reduction in dose of cyclosporin, and three had impairment of renal function (following long-term cyclosporin monotherapy) that improved, but did not normalize, following a reduction in dose of cyclosporin. In each case, combination treatment for psoriasis resulted in good control of both skin and joint problems using lower doses of each agent than would have been used for monotherapy. We conclude that the combination of methotrexate and cyclosporin is an effective treatment for this group of patients.

Severe exacerbation of psoriasis after cessation of methotrexate therapy successfully treated with cyclosporin A

“…Jednak ze względu na niezadowalający efekt terapeutyczny w krótkim czasie dołączono do leczenia cyklosporynę A i uzyskano szybką poprawę kliniczną. W dostępnym piśmiennictwie opisywano przypadki skutecznej terapii z zastosowaniem połączenia metotreksatu z cyklosporyną A ciężkiej, opornej na leczenie łuszczycy, w tym łuszczycy erytrodermicznej [6][7][8][9][10]. Stanowi ono potencjalną terapię alternatywną u tych chorych, którzy źle tolerują duże dawki pojedynczego leku lub nie osiągają wystarczającej poprawy przy stosowaniu tylko jednego z nich.…”

“…Combined treatment may lead to more rapid regression of cutaneous lesions, however it should be stressed that such therapy carries a greater risk of adverse reactions, particularly infectious complications [11]. On the other hand, based on the available data [6][7][8][9][10], methotrexate combined with cyclosporin A seems to be a relatively safe therapeutic modality, provided that follow-up examinations are systematically performed and the treatment is monitored on an ongoing basis. It is important to note, though, that data on the long-term safety of using this drug combination are insufficient.…”

“…However, since the therapeutic effect was unsatisfactory, cyclosporin A was added to the treatment regimen within a short time, leading to a rapid clinical improvement. The available literature describes cases of effective combination therapy with methotrexate and cyclosporin A in cases of severe treatment-refractory psoriasis including erythrodermic psoriasis [6][7][8][9][10]. It represents a potential alternative therapy in patients who do not tolerate well high doses of a single drug or whose condition fails to improve sufficiently in response to treatment based on one of the two medications.…”

Management of patients with psoriatic arthritis

“…По имеющимся данным, тера-пия БПВП при ПсА не способна замедлить деструктивные процессы в суставах. Эффективность комбинированной тера-пии различными БПВП имеет низкий уровень доказательно-сти и нуждается в более глубоком изучении [37,38].…”

Systemic Cyclosporin in the Treatment of Psoriasis

“…fumaric acid esters, methotrexate, mycophenolate mofetil) have been used in patients with severe psoriasis to facilitate cyclosporin dosage reduction and to reduce the risk of potential adverse effects . For instance, in small-scale, uncontrolled trials:  Cyclosporin plus methotrexate was administered for a mean of up to about 3½ years in 19 patients with severe recalcitrant psoriasis, and the combination schedule produced good control of psoriasis using lower doses of each agent than would have been used for monotherapy; however, 6 patients developed renal impairment, which normalised (n=3), or which improved but did not normalise (n=3), after cyclosporin dosage reduction (Clark et al, 1999).  Cyclosporin 2.5 mg/kg/day plus mycophenolate mofetil 3 g/day led to moderate or good clinical improvement over 3-11 months' follow-up in 78% of patients with severe recalcitrant psoriasis (Ameen et al, 2001).…”