Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics

Christopher T Ritchlin, Mona Stahle, Yves Poulin, Jerry Bagel, Soumya D Chakravarty, Shelly Kafka, Bhaskar Srivastava, Wayne Langholff, Alice B Gottlieb, Christopher T Ritchlin, Mona Stahle, Yves Poulin, Jerry Bagel, Soumya D Chakravarty, Shelly Kafka, Bhaskar Srivastava, Wayne Langholff, Alice B Gottlieb

Abstract

Background: Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients.

Methods: Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated.

Results: PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician's Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p < 0.05) in self-reported PsA patients. Biologic groups, other than ustekinumab, had numerically higher rates of SI.

Conclusions: PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure.

Trial registration: NCT00508547; Registered July 30, 2007.

Keywords: PSOLAR; Psoriasis; Psoriatic arthritis; Serious infections.

Conflict of interest statement

Competing interestsC. T. Ritchlin has received consultant fees (< $10,000) from Amgen, Eli Lilly, Janssen, Pfizer, and UCB, and consultant fees (> $10,000) from AbbVie. M. Stahle has received consultant/speaking/honoraria (<$10,000) from AbbVie, Eli Lilly, Leo Pharma, and Novartis. Y. Poulin has received consultant/speaking/ honoraria (<$10,000) from Amgen, Celgene, and Galderma, and fees (>$10,000) from AbbVie, Eli Lilly, Janssen, and Novartis. J. Bagel has received consultant fees (<$10,000) from Boehringer Ingelheim, and consultant/speaker/investigator fees (>$10,000) from Eli Lilly, Celgene, Janssen, Leo Pharma, Novartis, and Ortho Dermatologics. A. B. Gottlieb has received consultant/speaking/honoraria (<$10,000) from Beiersdorf, Merck, Novartis, and Valeant, and (>$10,000) from AbbVie, Eli Lilly, Janssen, Pfizer, and UCB. S. D. Chakravarty, S. Kafka, B. Srivastava, and W. Langholff are all employees of Janssen and own stock in Johnson & Johnson, of which Janssen is a wholly-owned subsidiary.

© The Author(s) 2019.

Figures

Fig. 1
Fig. 1
Predictors of time-to-first serious infection in PSOLAR psoriasis patients with self-reported PsA (overall population). CI, confidence interval; MTX, methotrexate; PGA, Physician’s Global Assessment; PsA, psoriatic arthritis; PSOLAR, Psoriasis Longitudinal Assessment and Registry; TNF, tumor necrosis factor

References

    1. Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(Suppl 2):ii14–ii17.
    1. Germano V, Cattaruzza MS, Osborn J, et al. Infection risk in rheumatoid arthritis and spondyloarthropathy patients under treatment with DMARDs, corticosteroids and TNF-α antagonists. J Transl Med. 2014;12:77. doi: 10.1186/1479-5876-12-77.
    1. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376:957–970. doi: 10.1056/NEJMra1505557.
    1. Garcia-Doval I, Cohen AD, Cazzaniga S, et al. Psonet Network. Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti-tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries. J Am Acad Dermatol. 2017;76:299–308.e16. doi: 10.1016/j.jaad.2016.07.039.
    1. Dávila-Seijo P, Dauden E, Descalzo MA, et al. BIOBADADERM Study Group. Infections in moderate to severe psoriasis patients treated with biological drugs compared to classic systemic drugs: findings from the BIOBADADERM registry. J Invest Dermatol. 2017;137:313–21.
    1. Yiu ZZ, Exton LS, Jabbar-Lopez Z, et al. Risk of serious infections in patients with psoriasis on biologic therapies: a systematic review and meta-analysis. J Invest Dermatol. 2016;136:1584–1591. doi: 10.1016/j.jid.2016.03.035.
    1. Kalb Robert E., Fiorentino David F., Lebwohl Mark G., Toole John, Poulin Yves, Cohen Arnon D., Goyal Kavitha, Fakharzadeh Steven, Calabro Stephen, Chevrier Marc, Langholff Wayne, You Yin, Leonardi Craig L. Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis. JAMA Dermatology. 2015;151(9):961. doi: 10.1001/jamadermatol.2015.0718.
    1. Minozzi S, Bonovas S, Lytras T, et al. Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. Expert Opin Drug Saf. 2016;15(sup1):11–34. doi: 10.1080/14740338.2016.1240783.
    1. Accortt NA, Bonafede MM, Collier DH, et al. Risk of subsequent infection among patients receiving tumor necrosis factor inhibitors and other disease-modifying antirheumatic drugs. Arthritis Rheumatol. 2016;68:67–76. doi: 10.1002/art.39416.
    1. Singh JA, Cameron C, Noorbaloochi S, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. 2015;386:258–265. doi: 10.1016/S0140-6736(14)61704-9.
    1. Subesinghe Sujith, Rutherford Andrew Ian, Byng-Maddick Rachel, Leanne Hyrich Kimme, Benjamin Galloway James. Recurrent serious infections in patients with rheumatoid arthritis—results from the British Society for Rheumatology Biologics Register. Rheumatology. 2018;57(4):651–655. doi: 10.1093/rheumatology/kex469.
    1. Richter A, Listing J, Schneider M, et al. Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1667–1673. doi: 10.1136/annrheumdis-2015-207838.
    1. Haddad A, Li S, Thavaneswaran A, et al. The incidence and predictors of infection in psoriasis and psoriatic arthritis: results from longitudinal observational cohorts. J Rheumatol. 2016;43:362–366. doi: 10.3899/jrheum.140067.
    1. Pérez-Plaza A., Carretero G., Ferrandiz C., Vanaclocha F., Gómez-García F.J., Herrera-Ceballos E., De la Cueva-Dobao P., Belinchón I., Sánchez-Carazo J.L., Alsina M., López-Estebaranz J.L., Ferrán M., Torrado R., Carrascosa J.M., Llamas-Velasco M., Rivera R., Jiménez-Puya R., García-Doval I., Descalzo M.A. Comparison of phenotype, comorbidities, therapy and adverse events between psoriatic patients with and without psoriatic arthritis. Biobadaderm registry. Journal of the European Academy of Dermatology and Venereology. 2017;31(6):1021–1028. doi: 10.1111/jdv.14188.
    1. Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73:529–535. doi: 10.1136/annrheumdis-2013-204575.
    1. Galloway JB, Hyrich KL, Mercer LK, et al. BSRBR Control Centre Consortium; British Society for Rheumatology Biologics Register. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology (Oxford) 2011;50:124–131. doi: 10.1093/rheumatology/keq242.
    1. Dommasch ED, Abuabara K, Shin DB, et al. The risk of infection and malignancy with tumor necrosis factor antagonists in adult patients with psoriatic disease: a systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2011;64:1035–1050. doi: 10.1016/j.jaad.2010.09.734.
    1. Papp KA, Strober B, Augustin M, et al. PSOLAR investigators and steering committee. PSOLAR: design, utility, and preliminary results of a prospective, international, disease-based registry of patients with psoriasis who are receiving, or are candidates for, conventional systemic treatments or biologic agents. J Drugs Dermatol. 2012;11:1210–1217.
    1. Gottlieb AB, Kalb RE, Langley RG, et al. Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies. J Drugs Dermatol. 2014;13:1441–1448.
    1. Kavanaugh A, Papp K, Gottlieb AB, et al. Demography, baseline disease characteristics, and treatment history of psoriasis patients with self-reported psoriatic arthritis enrolled in the PSOLAR registry. BMC Rheumatology. 2018;2:29. doi: 10.1186/s41927-018-0034-7.
    1. Dixon W. G., Watson K., Lunt M., Hyrich K. L., Silman A. J., Symmons D. P. M. Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Results from the British Society for Rheumatology Biologics Register. Arthritis & Rheumatism. 2006;54(8):2368–2376. doi: 10.1002/art.21978.
    1. Gómez-Reino JJ, Carmona L, Valverde VR, et al. BIOBADASER group. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum. 2003;48:2122–2127. doi: 10.1002/art.11137.
    1. Ritchlin Christopher, Rahman Proton, Kavanaugh Arthur, McInnes Iain B, Puig Lluis, Li Shu, Wang Yuhua, Shen Yaung-Kaung, Doyle Mittie K, Mendelsohn Alan M, Gottlieb Alice B. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Annals of the Rheumatic Diseases. 2014;73(6):990–999. doi: 10.1136/annrheumdis-2013-204655.
    1. Mease PJ, van der Heijde D, Ritchlin CT, et al. SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naïve patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76:79–87.
    1. Nash P, Kirkham B, Okada M, et al. SPIRIT-P2 study group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389:2317–2327. doi: 10.1016/S0140-6736(17)31429-0.
    1. Singh JA, Guvatt G, Ogdie A, et al. Special article: 2018 American College of Rheumatology/National Psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol. 2019;71:5–32.

Source: PubMed

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