Practical management of patients with psoriasis involves a process of assessing, informing, screening and monitoring. An initial consultation with the patient should cover aspects such as benefits of treatment, the risks (adverse effects) that may be encountered, details of the infusion procedure and generally improving overall patient awareness. Following the consultation, all patients must be screened to exclude latent tuberculosis, active infections, demyelinating diseases, malignancy or premalignancy, congestive heart failure (New York Heart Association III/IV), pregnancy and breast-feeding. Preprepared screening sheets are very useful for this exercise to ensure completeness. During treatment, assessment of efficacy is clearly very important, as is monitoring of safety (especially with regards to infections, malignancies, infusion-site reactions and autoantibodies). In this workshop, the focus was on the benefit–risk profile of biologic therapy and, based on feedback from the participants, the most important topics for discussion were infections, autoimmunity, cutaneous reactions, malignancies, infusion-site reactions and laboratory alterations.
With regards to tuberculosis, it was noted that tolerability is an issue when administering infliximab with antituberculosis drugs (particularly those containing isoniazid). This is a problem in regions where tuberculosis is endemic and many patients need to take chemoprophylaxis for a period of 9 months. In terms of other infections, isolated cases of generalized herpes zoster was reported by individual participants and, in the Spanish registry, herpes zoster infections were some of the most frequent recorded in patients receiving biologic therapy. The question arises as to what is the best practice for psoriasis patients who present with an infection and require treatment with a drug such as infliximab. This was an interesting discussion between the delegates and the general view was that usual clinical practice should be followed (physical examination) for patients with a mild infection.
Anti-TNF-α therapy could be started, or continued, as the case may be. Only in patients with severe infections was it felt necessary to discontinue biologic therapy. With respect to hepatitis B and C infections, the prevailing view was that they represent two very different treatment scenarios. It was generally considered that the use of biologics in patients with hepatitis C could be maintained (with proper care and follow-up), whereas this was not the case for hepatitis B, where the potential for a more serious drug–drug interaction was possible.
Most participants in the workshop had observed cases where small changes in liver enzymes had occurred during treatment with infliximab (5–10%), and these generally only required careful monitoring. More significant increases in transaminases (above three-times the upper limit of normal) were reported in isolated cases and these may require temporary discontinuation of infliximab therapy.
What are the issues concerning autoimmunity and do most practitioners routinely measure antibody levels? In a recent analysis in France, they found that almost three-quarters of patients on biologic therapy were positive for autoimmune antibodies (in 72% of cases antinuclear antibodies), but the clinical significance of this finding was unclear. Interestingly, the most frequent autoimmune disease associated with anti-TNF drugs was cutaneous leukocytoclastic vasculitis, followed by lupus-like syndrome and systemic lupus erythematosus. The clinical importance of the autoantibody issue was debated and it was generally felt that low titers 1:80, 1:160 and possibly up to 1:640 were not reasons for discontinuing infliximab therapy if no clinical symptoms were present; clearly, however, the patient should be monitored closely. Analysis of 92 patients with lupus-like syndrome associated with anti-TNF therapy (from a registry database) showed that the majority of cases occurred in patients with rheumatoid arthritis. The production of antinuclear antibodies represents only one aspect of autoimmunity; another aspect is the development of antibodies against the biologic agents themselves. These antibodies can potentially inactivate the drug and/or reduce its blood levels. There is evidence that antibodies develop against all the anti-TNF drugs, with some considered neutralizing and some non-neutralizing, and this is an area that requires further elucidation.
Financial & competing interests disclosure
E Dauden has the following conflict of interests: Advisory Board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking and research support with the following pharmaceutical companies: Abbott, Astellas, Biogen, Galderma, GlaxoSmithKline, Janssen-Cilag, Leo Pharma, Merck-Serono, Novartis, Schering-Plough, Wyeth Pharmaceuticals and 3M. D Thaci has consultant arangements with Abbott, Biogen, Essex/Schering-Plough and Wyeth, grants/research support from Abbott, Biogen, Essex/Schering-Plough, Wyeth and Serono, and is on the Speakers’ Bureau and received lecture honoraria from Abbott, Essex/Schering-Plough, Leo, Serono 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.