Failing Response to Infliximab
I have a 29-year-old male patient with psoriatic arthritis and skin involvement. He has been treated with infliximab since August 2003 with excellent response. He responded poorly to the last infusion at 3 mg/kg and also at 2-week 2 mg/kg. Is there an explanation for this lack of response, and what is your expert advice for my next course of action?

Vicente Juarez

The patient received periodic infliximab therapy for about 4 months and then developed relative refractory disease at 3 mg/kg. It is unclear whether the patient had concurrent methotrexate therapy. Previous studies have shown the benefit of infliximab at 5 mg/kg for plaque-like psoriasis using a protocol of dose at 2, 4, and 6 weeks followed by every 3 months. Another trial in psoriatic patients used infliximab at doses between 5 and 10 mg/kg. In rheumatoid arthritis, patients often start at 3 mg/kg but the dosage in practice often escalates with time. Thus, the patient may be relatively underdosed. In rheumatoid arthritis, patients are frequently started at 3 mg/kg (usually plus methotrexate) but still have an escalation of dose to 5 mg/kg or more. Initially, this escalation was attributed to formation of blocking antibodies, but recent studies have questioned this hypothesis. Kirby and colleagues have reported the benefit of combination of infliximab plus methotrexate in psoriasis. The reason for the synergy between methotrexate and infliximab remains unknown but may involve additional factors such as "blockage" of infliximab clearance. If the patient remains refractory to higher-dose infliximab plus methotrexate, then other options might include etanercept, efalizumab, alefacept, adalimumab or cyclosporine A.