Abstract
Purpose of Review
To summarize our most current understanding of the real world risk of infections associated with biologic and small molecule therapies in the setting of psoriatic disease.
Recent Findings
Patients with psoriasis or psoriatic arthritis are at increased risk for infection from both their disease and some of their therapies. There is little real world data for biologic and small molecule therapies; however, ustekinumab and biologics inhibiting IL-17 or IL-23 appear to have reduced risk estimates compared to anti-TNF therapies. Apremilast seems to have little infectious signal with limited real world data, and for JAK inhibitors, limited real world data suggest a higher risk of herpes zoster.
Summary
Recently approved targeted and small molecule therapies for psoriasis carry infectious risks for patients, although they appear to vary across mechanism of action. As these treatments become more widespread, and additional therapies are approved, it will be imperative to evaluate their safety in the context of real world data.
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References
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Helmick CG, Sacks JJ, Gelfand JM, Bebo B Jr, Lee-Han H, Baird T, et al. Psoriasis and psoriatic arthritis: a public health agenda. Am J Prev Med. 2013;44(4):424–6.
Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 2009;60(2):218–24.
Gelfand JM, Gladman DD, Mease PJ, Smith N, Margolis DJ, Nijsten T, et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol. 2005;53(4):573.
Alinaghi F, Calov M, Kristensen LE, et al. Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol. 2018.
Armstrong AW, Gelfand JM, Boehncke WH, Armstrong EJ. Cardiovascular comorbidities of psoriasis and psoriatic arthritis: a report from the GRAPPA 2012 annual meeting. J Rheumatol. 2013;40(8):1434–7.
Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:e54.
Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and hypertension: a systematic review and meta-analysis of observational studies. J Hypertens. 2013;31(3):433–42 discussion 442-433.
Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2(2):e000062.
Ma C, Harskamp CT, Armstrong EJ, Armstrong AW. The association between psoriasis and dyslipidaemia: a systematic review. Br J Dermatol. 2013;168(3):486–95.
Wakkee M, de Vries E, van den Haak P, Nijsten T. Increased risk of infectious disease requiring hospitalization among patients with psoriasis: a population-based cohort. J Am Acad Dermatol. 2011;65(6):1135–44.
Blauvelt A. New concepts in the pathogenesis and treatment of psoriasis: key roles for IL-23, IL-17A and TGF-β1. Expert Rev Dermatol. 2007;2:69–78.
Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496–509.
Kao LT, Lee CZ, Liu SP, Tsai MC, Lin HC. Psoriasis and the risk of pneumonia: a population-based study. PLoS One. 2014;9(12):e116077.
Haddad A, Li S, Thavaneswaran A, Cook RJ, Chandran V, Gladman DD. The incidence and predictors of infection in psoriasis and psoriatic arthritis: results from longitudinal observational cohorts. J Rheumatol. 2016;43(2):362–6.
Hsu DY, Gordon K, Silverberg JI. Serious infections in hospitalized patients with psoriasis in the United States. J Am Acad Dermatol. 2016;75(2):287–96.
•• Takeshita J, Shin DB, Ogdie A, Gelfand JM. Risk of serious infection, opportunistic infection, and herpes zoster among patients with psoriasis in the United Kingdom. J Invest Dermatol. 2018;138(8):1726–35 This is one of the first studies that identifies psoriasis severity, as measured by BSA, as contributing to risk of serious infection independent of other risk factors associated with psoriasis.
Grijalva CG, Chen L, Delzell E, Baddley JW, Beukelman T, Winthrop KL, et al. Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA. 2011;306(21):2331–9.
Baddley JW, Winthrop KL, Chen L, Liu L, Grijalva CG, Delzell E, et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) study. Ann Rheum Dis. 2014;73(11):1942–8.
Papp KA, Strober B, Augustin M, Calabro S, Londhe A, Chevrier M, et al. 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(10):1210–7.
Kalb RE, Fiorentino DF, Lebwohl MG, Toole J, Poulin Y, Cohen AD, et al. Risk of serious infection with biologic and systemic treatment of psoriasis: results from the psoriasis longitudinal assessment and registry (PSOLAR). JAMA Dermatol. 2015;151:961–9.
Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the psoriasis longitudinal assessment and registry (PSOLAR). J Drugs Dermatol. 2015;14(7):706–14.
Davila-Seijo P, Dauden E, Descalzo MA, et al. 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(2):313–21.
Medina C, Carretero G, Ferrandiz C, Dauden E, Vanaclocha F, Gómez-García FJ, et al. Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry. J Eur Acad Dermatol Venereol. 2015;29(5):858–64.
• Yiu ZZN, Smith CH, Ashcroft DM, et al. Risk of serious infection in patients with psoriasis receiving biologic therapies: a prospective cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2018;138(3):534–41 This study is one of the best examples from a pharmacoepidemiology standpoint for exploring robust methods to reduce confounding between disparate groups.
Garcia-Doval I, Cohen AD, Cazzaniga S, Feldhamer I, Addis A, Carretero G, et al. 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(2):299–308 e216.
Garcia-Doval I, Rustenbach SJ, Stern R, Dam TN, Cohen AD, Baker C, et al. Systemic psoriasis therapy shows high between-country variation: a sign of unwarranted variation? Cross-sectional analysis of baseline data from the PSONET registries. Br J Dermatol. 2013;169(3):710–4.
Dobry AS, Quesenberry CP, Ray GT, Geier JL, Asgari MM. Serious infections among a large cohort of subjects with systemically treated psoriasis. J Am Acad Dermatol. 2017;77(5):838–44.
Winthrop KL, Furst DE. Rheumatoid arthritis and herpes zoster: risk and prevention in those treated with anti-tumour necrosis factor therapy. Ann Rheum Dis. 2010;69(10):1735–7.
Desai RJ, Bateman BT, Huybrechts KF, et al. Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study. BMJ. 2017;356:j895.
Abuabara K, Azfar RS, Shin DB, Neimann AL, Troxel AB, Gelfand JM. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol. 2010;163(3):586–92.
Strangfeld A, Eveslage M, Schneider M, Bergerhausen HJ, Klopsch T, Zink A, et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient? Ann Rheum Dis. 2011;70(11):1914–20.
WInthrop KL, Siegel SAR, Chen L, et al. Comparative infectious risk of immunosuppressive therapies used in psoriasis. J Psoriasis Psoriatic Arthritis. 2016;2(1):7.
Shalom G, Zisman D, Bitterman H, Harman-Boehm I, Greenberg-Dotan S, Dreiher J, et al. Systemic therapy for psoriasis and the risk of herpes zoster: a 500000 person-year study. JAMA Dermatol. 2015;151(5):533–8.
Shalom G, Naldi L, Lebwohl M, Nikkels A, de Jong EMGJ, Fakharzadeh S, et al. Biological treatment for psoriasis and the risk of herpes zoster: results from the psoriasis longitudinal assessment and registry (PSOLAR). J Dermatolog Treat. 2018:1–20.
Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–39.
van den Reek J, van Vugt LJ, van Doorn MBA, et al. Initial results of secukinumab drug survival in patients with psoriasis: a multicentre daily practice cohort study. Acta Derm Venereol. 2018;98(7):648–54.
van der Heijde D, Gladman DD, Kishimoto M, Okada M, Rathmann SS, Moriarty SR, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase III study (SPIRIT-P1). J Rheumatol. 2018;45(3):367–77.
Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, et al. Ixekizumab for the treatment of psoriasis: a review of phase III trials. Dermatol Ther (Heidelb). 2016;6(1):25–37.
Papp KA, Barber K, Bissonnette R, Bourcier M, Lynde CW, Poulin Y, et al. A Randomized, blinded assessor study to Evaluate the efFIcacy and safety of etanercept 50 mg once weekly plus as Needed topical agent vs. Etanercept 50 mg twice weekly in patients with moderate to severe plaque psoriasis (REFINE). J Eur Acad Dermatol Venereol. 2015;29(2):361–6.
Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015;373(2):136–44.
Howell ST, Cardwell LA, Feldman SR. Treating moderate-to-severe plaque psoriasis with guselkumab: a review of phase II and phase III trials. Ann Pharmacother. 2018;52(4):380–7.
Deodhar A, Gottlieb AB, Boehncke WH, Dong B, Wang Y, Zhuang Y, et al. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2018;391(10136):2213–24.
Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405–17.
Keating GM. Apremilast: a review in psoriasis and psoriatic arthritis. Drugs. 2017;77(4):459–72.
Stein Gold L, Bagel J, Lebwohl M, Jackson JM, Chen R, Goncalves J, et al. Efficacy and safety of apremilast in systemic- and biologic-naive patients with moderate plaque psoriasis: 52-week results of UNVEIL. J Drugs Dermatol. 2018;17(2):221–8.
Wells AF, Edwards CJ, Kivitz AJ, Bird P, Nguyen D, Paris M, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. Rheumatology (Oxford). 2018;57:1253–63.
Strober B, Bagel J, Lebwohl M, Stein Gold L, Jackson JM, Chen R, et al. Efficacy and safety of apremilast in patients with moderate plaque psoriasis with lower BSA: week 16 results from the UNVEIL study. J Drugs Dermatol. 2017;16(8):801–8.
Kishimoto M, Komine M, Hioki T, Kamiya K, Sugai J, Ohtsuki M. Real-world use of apremilast for patients with psoriasis in Japan. J Dermatol. 2018;45:1345–8.
Elyoussfi S, Thomas BJ, Ciurtin C. Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies. Rheumatol Int. 2016;36:603–12.
Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843–7.
Winthrop KL, Lebwohl M, Cohen AD, Weinberg JM, Tyring SK, Rottinghaus ST, et al. Herpes zoster in psoriasis patients treated with tofacitinib. J Am Acad Dermatol. 2017;77(2):302–9.
FDA. FDA Briefing Document: Arthritis Advisory Committee Meeting. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM569317.pdf. Published 2017. Accessed February 18, 2019.
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Sarah Siegel has no conflicts of interest. Dr. Winthrop reports grants and personal fees from Pfizer, grants and personal fees from BMS, personal fees from AbbVie, personal fees from UCB, personal fees from Lilly, personal fees from Galapagos, personal fees from GSK, personal fees from Roche, and personal fees from Gilead, outside the submitted work.
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Siegel, S.A.R., Winthrop, K.L. In the Real World: Infections Associated with Biologic and Small Molecule Therapies in Psoriatic Arthritis and Psoriasis. Curr Rheumatol Rep 21, 36 (2019). https://doi.org/10.1007/s11926-019-0832-y
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DOI: https://doi.org/10.1007/s11926-019-0832-y