TNF-alpha Inhibitors Linked to Lower Psoriatic Arthritis Risk in Psoriasis: Ten-Year Cohort Study

Over the past five years, several publications have examined the effect of systemic psoriasis treatment on the development of psoriatic arthritis. Some of these publications support the concept that treating psoriasis reduces the incidence of PsA. Other publications suggest an increased incidence of PsA among patients with PsO treated with biologics.

This longitudinal cohort study was designed to compare the ten-year cumulative incidence of PsA in two groups of patients with severe psoriasis: one group was treated with TNF alpha inhibitors (TNFi), while the other received narrow-band ultraviolet B (nbUVB) phototherapy. To address the limitations of prior studies, Piaserico et al used PS matching analysis of a cohort of patients. All consecutive adult patients from five Italian centers were included if they were prescribed TNFi treatment (etanercept, infliximab, and adalimumab) or nbUVB therapy for chronic plaque psoriasis between September 2005 and September 2010. Patients with a history of PsA or PsA at baseline were excluded. A 1:1 PS-matched cohort was created via nearest neighbor matching with a calliper of 0.2 to avoid indication bias. Unmatched patients were excluded. The study shows that continuous, long-term treatment approaching a decade with TNFi significantly decreases the incidence of PsA in severe psoriasis patients compared with long-term nbUVB phototherapy.  A total of 98 (16.5%) patients developed PsA: 32 (10.7%) in the cohort treated with TNFi and 66 (22.2%) in the Phototherapy group. The incidence rate of PsA cases per 100 psoriasis patients was 1.83 (95% CI: 1.632–2.028) in the whole population and 1.18 (0.84–1.52) and 2.48 (2.24–2.72) in the TNFi and nbUVB cohorts, respectively. The IRR was 2.1 (1.37–2.98, P: 0.0002). The cumulative incidence of PsA was 5.5 and 7.1 at five years and 10.6 and 18.3 at ten years.

Previous studies addressing this question suffered from many biases due to their retrospective nature. While PS matching might help avoid confounding variables and reduce treatment selection bias, it cannot entirely replace a randomized trial. This matching strategy aimed to mitigate protopathic bias, a potential confounding factor that may have influenced analyses in earlier studies. But baseline analysis shows more patients in the TNFi group suffered from arthralgia, creating an imbalance between cohorts. Arthralgia represents a clear risk factor for developing psoriatic arthritis and might have influenced TNFi selection, since phototherapy does not affect arthritis. In previous retrospective studies, arthralgia at baseline was not evaluated, making it difficult to understand its incidence in the treatment selection. In this study, arthralgia patients had an attenuated protective effect from TNFi treatment, reinforcing its association with the development of PsA.

On the other hand, more patients with nail psoriasis were included in the phototherapy group, which is also a known risk factor for PsA, and this could, in part, have an impact on the reduced effect on arthritis development. Since phototherapy has no systemic immunosuppressive effects, the protective role of prolonged TNFi therapy on the development of PsA could be attributed to more effective control of psoriasis remission, which is supported by the recognized association between psoriasis disease activity and PsA risk. Some studies reported a reduction in the development of PsA in psoriatic patients treated with biologics. But others show an increased incidence of patients on systemic treatment, probably because more severe patients are treated with biologicals, and have a higher risk of PsA development.  Conflicting results arise since some studies are not controlled, some use short-term follow-up, and some retrospective studies suffer from many biases.

In summary, this article by Piaserico brings more light to a controversial issue. Nevertheless, a lack of evidence still needs randomized trial information to answer. Should we treat patients with known risk factors for developing Psoriatic arthritis, like arthralgia, more aggressively? Should we keep these patients ON treatment for more extended periods? Should we not try de-escalating them? Is this strategy cost-effective? What about mild to moderate psoriasis patients with risk factors for developing arthritis? This excellent article adds new data, but many unanswered questions remain.