GOTHENBURG, SWEDEN – For psoriasis patients, all tumor necrosis factor inhibitors are associated with roughly the same risks for serious infection, according to a meta-analysis of data from major randomized clinical trials and their long-term, open-label extensions.
Regardless of whether etanercept, infliximab, or adalimumab was the prescribed agent, the serious infection risk for psoriasis patients was in the range of 1.0-1.5 cases per 100 patient-years of therapy. Thus, 1 in every 10 patients on any given TNF-inhibitor could expect to have about one serious skin infection every 10 years, Dr. Richard Langley said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology.
"Serious" infections in this context may or may not be a big deal. A serious infection, under the definition employed in the clinical trials, is one requiring intravenous antibiotics or hospitalization. The number-needed-to-harm – that is, the number of psoriasis patients who would need to be treated with an anti-TNF biologic rather than placebo for 1 year in order to cause one additional serious infection – is at least two orders of magnitude larger than the number-needed-to-treat in order to achieve a PASI 75 treatment response. That’s an extremely favorable risk-benefit ratio, said Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, Nova Scotia.
His recently published meta-analysis (Br. J. Dermatol. 2010 Apr 14 [Epub ahead of print]) showed that the number-needed-to-treat was 1.4 patients with infliximab dosed at 5 mg/kg, 1.6 for adalimumab at 40 mg every 2 weeks, 2.3 for etanercept at 50 mg twice weekly, and 3.2 for etanercept at 50 mg once weekly or 25 mg twice weekly, he reported at the satellite symposium sponsored by Abbott.
Serious infections warrant a temporary interruption of anti-TNF therapy. But so do clinically important infections that don’t rise to the threshold of "serious," he said, for example, a case of cellulitis being treated on an outpatient basis with oral antibiotics. Continuing anti-TNF therapy in such a patient increases the risk of a more complicated infection.
"I would submit to you that it’s better to be conservative in situations like this and withhold therapy," he said.
All of the TNF inhibitors – indeed, probably all biologic therapies – increase the risk of upper respiratory infections, bronchitis, and nasopharyngitis. These are minor infections, and it’s generally appropriate to push ahead with therapy, as was routine practice in the clinical trials, Dr. Langley noted.
However, participants in clinical trials are a carefully selected subgroup. They often are quite dissimilar in key ways to patients encountered in daily clinical practice. Registry data better reflect real-world patients. And while registries of psoriasis patients on biologic therapies are now up and running, the follow-up isn’t yet sufficiently long for data analysis.
Dermatologists seeking to gain a fuller understanding of the safety issues surrounding the TNF antagonists can turn to the rheumatology experience with biologics. British Society for Rheumatology Biologics Registry data show an incidence of skin and soft tissue infections in rheumatoid arthritis patients that is 3.0 cases per 1,000 patient-years of treatment with methotrexate or other traditional disease-modifying anti-rheumatic drugs (DMARDs) and 12.0 per 1,000 patient-years in those on TNF inhibitors, for an adjusted 4.3-fold increased relative risk accompanying the newer agents (Arthritis Rheum. 2006 54:2,368-76).
But it’s important to remember that psoriasis patients differ in important ways from those with rheumatoid arthritis, Dr. Langley noted. The arthritis patients are much more likely, for example, to be on concomitant treatment with systemic corticosteroids, and perhaps to have intrinsic disease-related qualities predisposing to serious infections.
This point was effectively underscored in a formal analysis of serious adverse events in clinical trials of adalimumab across all indications (Ann. Rheum. Dis. 2009;68:1,863-9). The incidence of serious infections per 100 patient-years of exposure to adalimumab was 4.7 for rheumatoid arthritis patients, compared with 1.3 in those being treated for psoriasis.
Dr. Langley disclosed serving as a speaker for Abbott and having financial relationships with numerous other pharmaceutical companies that manufacture psoriasis therapies.