Biologic use in psoriasis may increase PsA incidence vs. phototherapy, oral therapies
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Patients with psoriasis who use biologics are more likely to develop psoriatic arthritis than those on other or no therapies, according to retrospective data published in the Annals of the Rheumatic Diseases.
“Given the shared pathogenetic pathways (tumor necrosis factor (TNF), IL-17), one would expect the treatment of psoriasis to be associated with reduced progression to clinically overt PsA,” Elana Meer, an MD/MBA candidate at the University of Pennsylvania, in Philadelphia, and colleagues wrote. “Furthermore, biologics, such as TNF alpha inhibitors, IL17i, 12/23i and IL23i, have demonstrated a clear benefit in improving the signs and symptoms of both psoriasis and PsA.”
“However, the relationship between a treatment for psoriasis and resulting PsA may be confusing in that some biologic therapies and retinoids have been purported to result in altered stimulation of the immune system, which has led to the paradoxical onset of PsA or the onset of pustular psoriasis among TNF inhibitor (TNFi) users,” they added. “Studies addressing the impact of therapy for psoriasis on development of PsA are lacking.”
To analyze the link between the use of biologic therapy in patients with psoriasis and the development of PsA, Meer and colleagues conducted a retrospective cohort study of the OptumInsights Electronic Health Record Database. According to the researchers, OptumInsights is a longitudinal database of electronic health records from dozens of health care organizations, including more than 150,000 providers, 2,000 hospitals and 7,000 clinics.
Focusing on the period between 2006 and 2017, the researchers included 193,709 patients with psoriasis without PsA, between the ages of 16 and 90 years, who started either oral or biologic drugs, or phototherapy. Meer and colleagues then determined the incidence of PsA within each therapy group. The analysis included multivariate Cox models to calculate hazard ratios for biologic versus oral or phototherapy, using biologics as a time-varying exposure and in a propensity score-matched cohort.
Among the included patients, 14,569 were using biologics while a combined 20,321 were receiving either oral or phototherapy. According to the researchers, PsA incidence, regardless of therapy exposure, was 9.75 per 1,000 person-years, compared with 77.26 among biologic users, 61.99 among oral therapy users, 26.11 among phototherapy users and 5.85 among those not receiving any of the target therapies.
After multivariable adjustment with time-varying exposure, the adjusted hazard ratio for biologic users was 4.48 (95% CI, 4.23-4.75), compared with those who received oral or phototherapy. After propensity score matching, the hazard ratio for the biologics group was 2.14 (95% CI, 2-2.28) compared with the other therapies.
“In this retrospective cohort study, patients with psoriasis initiating biologic therapy were more likely to develop PsA than patients initiating phototherapy or oral therapies or those not receiving therapy,” Meer and colleagues wrote. “Caution should be used in interpreting retrospective studies of the impact of biologic therapy on development of PsA. Future randomized controlled trials with long-term follow-up are needed to address the impact of therapy for psoriasis on the prevention of and/or the delay in development of PsA.”
Perspective
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A central tenet of modern therapeutic strategies is that earlier – and more aggressive – treatment of inflammation results in better overall outcomes. This has been shown conclusively in rheumatoid arthritis, where numerous studies have reported that treatment with biologic agents as soon as possible following diagnosis not only leads to reduction in signs and symptoms of the disease, but reduction in radiographic progression and improved health-related quality of life.
With regard to psoriatic arthritis, however, the situation may not be that clear. Psoriatic arthritis (PsA) develops over time in approximately 30% of patients with psoriasis. Thus, it is reasonable to extrapolate from the RA experience that earlier initiation of biologic agents for treatment of skin disease may affect the likelihood of subsequent development of joint symptoms.
The recent study by Meer and colleagues suggests the opposite; that early use of biologic agents in patients with psoriasis may actually increase the likelihood of developing PsA as compared to other therapies. This retrospective cohort study of over 190,000 patients with psoriasis followed longitudinally in the OptumInsights EHR found that the PsA incidence per 1000 person-years was 77.26 for patients on biologics as compared to only 61.99 on oral therapy, 26.11 on phototherapy and 9.75 overall.
These results should not be interpreted to suggest that earlier treatment of psoriasis with biologics cause PsA. As the authors themselves point out, there are several biases inherent in retrospective studies, not the least of which is the composition of the populations studied. Selection of a therapy for a given patient is motivated by many factors and these were not defined in this study (confounding by indication). Further, patients may be prescribed a biologic because there is either a perceived increased risk for PsA or symptoms that may suggest early PsA (protopathic bias).
Of note, the findings in this study are in contrast with several others that reported a decreased incidence of PsA in the biologics cohort compared with phototherapy and no therapy. Database analyses are useful for generating hypotheses, but randomized controlled trials, with long-term follow-up will be needed to address whether therapy for psoriasis prevents or delays the onset of PsA.
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