Commentary

A Boxed Warning for Inadequate Psoriasis Treatment

Cutis. 2016 September;98(3):206-207

Karen C. Kagha, BA

Andrew Blauvelt, MD, MBA

Kathryn L. Anderson, BS

Craig L. Leonardi, MD

Steven R. Feldman, MD, PhD

PDF Download

References

US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for industry: warning and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products—content and format. US Food and Drug Administration website. http://www.fda.gov/downloads/Drugs/.../Guidances/ucm075096.pdf. Published October 6, 2011. Accessed August 10, 2016.
Ogdie A, Yu Y, Haynes K, et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis. 2015;74:326-332.
Rose S, Sheth NH, Baker JF, et al. A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study. Am J Cardiovasc Dis. 2013;3:273-278.
Shlyankevich J, Mehta NN, Krueger JG, et al. Accumulating evidence for the association and shared pathogenic mechanisms between psoriasis and cardiovascular-related comorbidities. Am J Med. 2014;127:1148-1153.
Lee MK, Kim HS, Cho EB, et al. A study of awareness and screening behavior of cardiovascular risk factors in patients with psoriasis and dermatologists. Ann Dermatol. 2015;27:59-65.
Voiculescu VM, Lupu M, Papagheorghe L, et al. Psoriasis and metabolic syndrome—scientific evidence and therapeutic implications. J Med Life. 2014;7:468-471.
Wu JJ, Poon KY, Bebchuk JD. Association between the type and length of tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. J Drugs Dermatol. 2013;12:899-903.
Famenini S, Sako EY, Wu JJ. Effect of treating psoriasis on cardiovascular comorbidities: focus on TNF inhibitors. Am J Clin Dermatol. 2014;15:45-50.
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.
Chimenti MS, Graceffa D, Perricone R. Anti-TNFα discontinuation in rheumatoid and psoriatic arthritis: is it possible after disease remission [published online Apr 21, 2011]? Autoimmun Rev. 2011;10:636-640.
Kavanaugh A, Ritchlin C, Rahman P, et al. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73:1000-1006.
Pietrzak A, Bartosinska J, Blaszczyk R, et al. Increased serum level of N-terminal Pro-B-type natriuretic peptide as a possible biomarker of cardiovascular risk in psoriatic patients. J Eur Acad Dermatol Venereol. 2015;29:1010-1014.
Rapp SR, Feldman SR, Exum ML, et al. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3, pt 1):401-407.
Pettey AA, Balkrishnan R, Rapp SR, et al. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol. 2003;49:271-275.
Garshick MK, Kimball AB. Psoriasis and the life cycle of persistent life effects. Dermatol Clin. 2015;33:25-39.
Feldman SR, Malakouti M, Koo JY. Social impact of the burden of psoriasis: effects on patients and practice. Dermatol Online J. August 17, 2014;20. pii:13030/qt48r4w8h2.
Brezinski EA, Dhillon JS, Armstrong AW. Economic burden of psoriasis in the United States: a systematic review. JAMA Dermatol. 2015;151:651-658.

The US Food and Drug Administration uses the term boxed warning to highlight potentially dangerous situations associated with prescription drugs. A boxed warning is used when “[T]here is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using the drug.”¹ However, drugs are not the only potential cause of severe adverse outcomes in patients with psoriasis. Untreated psoriasis also is a well-established cause of serious morbidity and mortality. What are the risks of inadequate psoriasis treatment?

Psoriasis is associated with an increased risk for cardiovascular disease.^2-4 Patients with psoriasis also have a higher prevalence of classic cardiovascular risk factors including smoking, diabetes mellitus, hypertension, obesity, and hyperlipidemia.^5,6Psoriasis is a T-cell mediated disease process driven by IL-23 and T_H17 helper cell–derived proinflammatory cytokines, sharing certain genetic aspects with metabolic syndrome.⁶ Cytokine actions on insulin signaling, lipid metabolism, and adipogenesis may underlie the increased prevalence of metabolic syndrome and cardiovascular risk factors in patients with psoriasis. In addition to treating the cutaneous manifestations of psoriasis, reducing inflammation in these patients reduces C-reactive protein and lipid peroxidation and increases high-density lipoprotein levels.⁶ Tumor necrosis factor α blockers decrease the risk for cardiovascular disease in patients with psoriasis.^7,8Lower than expected rates of cardiovascular disease also have been reported in a large cohort of psoriasis patients (ie, PSOLAR [Psoriasis Longitudinal Assessment and Registry] registry) being treated with either ustekinumab or tumor necrosis factor α blockers.⁹

Psoriatic arthritis is a chronic inflammatory disease in which active inflammation results in progressive joint destruction.¹⁰ Tumor necrosis factor α inhibitors suppress disease progression, preserve function, and delay destruction of the joints. Ustekinumab also helps control psoriatic arthritis and inhibits radiographic progression of joint disease.¹¹

A Boxed Warning for Inadequate Psoriasis Treatment

References

Pages

Recommended Reading