Background:One of the strongest known risk factors for the development of psoriatic arthritis (PsA) is psoriasis. A key question is whether treatment of psoriasis may prevent or delay onset of PsA.Objectives:To compare the incidence of PsA among patients with psoriasis treated with a biologic compared to those treated with a non-biologic therapy for psoriasisMethods:We performed a retrospective cohort study in the Optum de-identified Electronic Health Record dataset between 2006-2017. Patients with two or more ICD codes for psoriasis between the ages of 16 and 90, who were initiating an oral medication, a biologic therapy, or phototherapy (defined as no preceding codes for the therapy in the prior 12 months) were identified. Covariates at baseline were determined in the 12 months prior to therapy initiation. The outcome of interest was PsA as defined by one ICD code. The incidence of PsA was described overall and within each therapy group. We analyzed the data in two ways: a) a multivariable Cox model using a time varying exposure (once the patient was exposed to a biologic, they were considered always exposed) derived from automated stepwise regression and b) propensity score matching (greedy matching, caliper 0.1) between biologic-exposed patients and oral/phototherapy exposed patients.Results:Among 215,386 patients with psoriasis without PsA at baseline, 9,848 were excluded for prior biologic exposure, and among the remaining, 60,258 initiated phototherapy, oral or biologic therapy during follow up. Among 22,461 new biologic initiations, 29,121 oral therapy and 8,676 phototherapy initiations, the mean age was lower in the biologics group compared to the non-biologic groups (46.9 vs 50.8), with a similar proportion of females and Caucasians. Observational time was also similar. A total of 1,643, 1,813, and 122 new PsA cases occurred over 60,739, 85,670, and 28,528 person/years (PY) of follow up, respectively (incidence 27.1, 21.2 and 4.2 per 1,000 person years respectively). Using a traditional multivariable adjustment approach with time varying exposure, the age and sex adjusted and fully adjusted HR (95% CI) for biologic users were 1.01 (0.99-1.04) and 0.93 (0.91-0.95), respectively. However, after propensity score matching, the HR (95% CI) was 1.64 (1.51-1.77). Survival curves cross, however, at approximately 8 years (Figure 1) and most of the new diagnoses of PsA occurred shortly after therapy initiation (Figure 2).Conclusion:Confounding by indication or protopathic bias may explain the observed association of biologic therapy with the development of PsA among patients with psoriasis. Some patients may be receiving therapy because they have both psoriasis and early symptoms of PsA or their PsA diagnosis is not recorded appropriately. Given the directional discrepancy in the results between traditional modeling and propensity score analysis, further work is needed to understand the nature of this relationship.FigureFigure 3.Directed Acyclic Graphdescribing potential confounders in relationship between therapy prescription and diagnosis of PsADisclosure of Interests:Alexis Ogdie Grant/research support from: Pfizer, Novartis, Consultant of: Abbvie, Amgen, BMS, Celgene, Corrona, Janssen, Lilly, Pfizer, Novartis, Thorvardur Love: None declared, Junko Takeshita: None declared, Joel Gelfand Grant/research support from: grants (to the Trustees of the University of Pennsylvania) from Abbvie, Boehringer Ingelheim, Janssen, Novartis Corp, Celgene, Ortho Dermatologics, and Pfizer Inc., Consultant of: BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), Dr. Reddy’s Labs, Pfizer Inc., and Sun Pharma, Paid instructor for: received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly, Ortho Dermatologics and Novartis., Jose Scher Consultant of: Novartis, Janssen, UCB, Sanofi., Hyon Choi Grant/research support from: Ironwood, Horizon, Consultant of: Takeda, Selecta, Horizon, Kowa, Vaxart, Ironwood, Robert Fitzsimmons: None declared, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma
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