The findings from a study (RESTORE1) comparing infliximab to methotrexate in the treatment of patients with moderate-to-severe plaque psoriasis have been published in the British Journal of Dermatology.

The authors note that methotrexate is commonly prescribed for the treatment of moderate-to-severe plaque psoriasis; however this is associated with myelosuppression and hepatotoxicity, and clinical efficacy and optimal dosing regimens are uncertain from the currently available data.  Three placebo-controlled studies have evaluated infliximab in the treatment of plaque psoriasis; this is the first to compare it to methotrexate.

The Phase IIIb study included a total of 868 adult patients with a diagnosis of moderate-to-severe plaque psoriasis made at least six months prior to screening, who were candidates for systemic treatment or phototherapy, and who had at least 10% of their total body surface are affected and a Psoriasis Area and Severity Index (PASI) ≥ 12.  They were randomised to treatment with infliximab (5mg/kg at week 0, 2, 6, 14 and 22) or methotrexate (15mg weekly, increased to 20mg at week 6 if needed); those not achieving a PASI 50 response (≥ 50% improvement in PASI from baseline) at week 16 or who were intolerant to treatment could switch treatment groups.   The primary endpoint was PASI 75 response at week 16.

The authors report that the primary endpoint was achieved by 78% of patients randomised to infliximab and 42% of those treated with methotrexate (P<0.001); other secondary endpoints were also reported to have been achieved by more patients in the infliximab group.  Similar responses were observed at week 26 in patients who switched from methotrexate to infliximab at week 16.

The most common treatment-related adverse events seen up to week 16 in the methotrexate group included nasopharyngitis (5%), fatigue (8%), headache (7%) and nausea (7%). In the infliximab group, they were infusion-related reactions (9%), nasopharyngitis (6%) and headache (5%). Infusion-related reactions were mild in 3% (21/649), moderate in 5% (34/649) and severe in 3% (19/649) of patients.  During this time serious adverse events were reported by 6% of the infliximab group and 2% of the methotrexate group.  A similar proportion of patients in each group experienced a serious infection.  The authors note that the crossover design complicated the assessment and interpretation of adverse events, and that the open label design may have led to bias in their reporting.

The authors conclude that their results suggest infliximab may be superior to methotrexate in the treatment of methotrexate-naïve patients with moderate-to-severe plaque psoriasis, but acknowledge that larger, longer-term double-blind studies are required for confirmation.