As a prelude to this workshop on long-term treatment, A Ogilvie presented the clinical findings from her clinic in Germany where they have been treating patients with moderate-to-severe psoriasis with infliximab since 1998. The European Infliximab for Psoriasis Efficacy and Safety (EXPRESS) study reported results for patients treated for up to 1 year and demonstrated that approximately 70% achieved the Psoriasis Assessment and Severity Index (PASI)-75 or better. Since psoriasis is potentially a life-long disease, what about longer term treatment? In the clinic in Erlangen, Germany, there are infliximab-treated patients who have been followed for up to 6 years and, despite the small numbers involved, the encouraging finding is that mean PASI scores have been maintained at very low levels. A published report relating to a subgroup of patients who had been followed for over 2 years showed that, at this time point, mean PASI was about one and, with regards to the treatment regimen, 29% were on infliximab monotherapy, 43% were receiving concomitant methotrexate, 7% concomitant steroids and 21% infliximab plus a combination of other disease-modifying drugs plus steroids.
M Papoutsaki presented data from Rome, Italy, where they have been using infliximab for 7 years and have treated 249 patients (123 with plaque-type psoriasis and 126 with psoriatic arthritis). The Rome group has data for a significant number of psoriasis patients who have been treated for 5 or more years, and an important clinical finding is that the therapeutic efficacy of infliximab is maintained in the long term, with many patients achieving PASI-75 and PASI-90.
The goal of the workshop was to brainstorm and discuss how to optimize long-term treatment with infliximab; possible topics to address included:
• Treatment success and failure
• Systemic comedication with infliximab; addition of methotrexate
• Infliximab-free long-term treatment, dosage reductions, dosage increases and timing
• Treatment intervals, continuous versus intermittent
• Patient satisfaction and patient demands
The participants of the workshop voted for the most relevant topics to debate and, almost unanimously, the three chosen topics were:
• Dosage
• Dosage interval
• Comedication
The participants of the workshop divided into groups and discussed these three topics with reference to infliximab and any patient that they had a notable success with or who had presented a particular challenge. Wide-ranging debate followed, which highlighted a number of differences in routine practice with the TNF-α antagonist. Some of the main points of interest included:
• Dosage was almost universally maintained at 5 mg/kg; individual participants acknowledged that they occasionally increased the dosage to 7.5 mg/kg in some patients to try and improve the response, while others occasionally reduced the dosage to 3 mg/kg;
• If the response to infliximab was reduced after time, a drug such as methotrexate (and, to a lesser extent, ciclosporin) was attempted by many of the physicians while others indicated that they reduced the infliximab dosage interval from 8 to 6 weeks (4 weeks in one case);
• The most common problems in day-to-day practice were reasonably consistent and included issues such as cost/reimbursement and loss of efficacy/relapse.
Providing a perspective for these discussions, data was presented from over 200 patients treated with infliximab in the Rome clinic. Infliximab has been shown to have a rapid onset of action and, to date, it has produced sustained activity for up to 4–5 years of continuous therapy. Temporary reductions in efficacy have been observed, but usually control of the psoriasis can be regained using a number of simple techniques that include the following:
• Monitoring the patient for two infusion periods, since some patients improve without changing anything;
• If the patient shows a persistent loss of efficacy, then adding methotrexate 7.5–15 mg/week to the treatment regimen is an option. The addition of methotrexate is temporary until the efficacy is regained (4–6 months);
• If the patient reports disease control that is less than the 8-week infusion period then they are observed for two infusions (since this can improve) and, if the problem persists, the time between infusions is reduced. This is a temporary reduction until the efficacy is regained (it usually takes two to three infusions);
• If the loss of efficacy is minimal (the patient maintains PASI-75 but small plaques develop and persist), topical therapy is generally used.
Based on these recommendations, the Rome group has treated 249 patients to date with the following results: 28 of 249 required additional methotrexate and 15 of 249 required a reduction in dosage interval. Interestingly, increasing the dose of infliximab was not as effective as reducing the dosage interval. The Rome group also formally compared long-term (120 weeks) continuous infliximab therapy with intermittent therapy and found that continuous therapy was significantly superior to intermittent therapy with regards to the percentage of patients achieving PASI-75. Both treatment groups initially produced a PASI-75 in approximately 80% of patients, which was maintained in the continuous therapy group. However, in the intermittent group, the percentage of patients with PASI-75 during treatment was reduced to approximately 45%. Following cessation of infliximab, the median time to relapse was approximately 182 days, which provides a relatively long treatment-free period, but reinstitution of therapy was not so effective in achieving PASI-75 in the intermittent treatment group. The results with respect to quality of life improvement almost directly correlated to the symptomatic results observed with PASI scores. Based on these findings in terms of symptomatology and quality of life, continuous therapy with infliximab appears to be significantly and clinically superior to intermittent therapy.
Financial & competing interests disclosure
M Papoutsaki has served as a consultant and speaker for Schering-Plough and Abbott. A Ogilvie has served as a consultant and speaker for Schering-Plough, Abbott and Wyeth. Writing assistance was provided by Steve Clissold PhD (Content Ed Net), with funding by Schering-Plough, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.