Martin A. Menter M.D.

Strober, B. E., R. G. B. Langley, A. Menter, M. Magid, B. Porter, T. Fox, J. Safi, Jr. and C. Papavassilis (2017). “No elevated risk for depression, anxiety, or suicidality with secukinumab in a pooled analysis of data from 10 clinical studies in moderate-to-severe plaque psoriasis.” Br J Dermatol: 2017 Oct [Epub ahead of print].

Full text of this article.

Concerns have emerged over the potential for brodalumab, a monoclonal antibody that binds to the human interleukin (IL)-17 receptor A and blocks the activity of multiple IL-17 isoforms, to increase risk of suicidal ideation and behaviour. Although the validity of this association has been questioned,1,2 brodalumab has a boxed warning regarding suicidality in its US label and is only available through a Risk Evaluation and Mitigation Strategy. Regardless of the true association between suicidality and brodalumab, the demonstrated adverse impact of psoriasis on mental health necessitates careful assessment for possible psychiatric adverse effects of psoriasis therapies, including those that inhibit the IL-17 pathway.

Roostaeyan, O., D. Kivelevitch and A. Menter (2017). “A review article on brodalumab in the treatment of moderate-to-severe plaque psoriasis.” Immunotherapy 9(12): 963-978.

Full text of this article.

Psoriasis is a chronic immune-mediated skin disorder affecting approximately 2-3% of the worldwide population. Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-17, a pro-inflammatory cytokine, plays a pivotal role in psoriasis. Therapeutic agents targeting this cytokine have shown clinical effectiveness in the treatment of moderate-to-severe plaque psoriasis. Brodalumab, a human antibody against IL-17 receptor A, has been approved by the US FDA in February 2017, by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 and by the EMA in July 2017 for the treatment of moderate-to-severe psoriasis. This article reviews the published data relating to brodalumab for the treatment of moderate-to-severe plaque psoriasis.

Frieder, J., D. Kivelevitch, I. Haugh, I. Watson and A. Menter (2017). “Anti-il-23 and anti-il-17 biologic agents for the treatment of immune-mediated inflammatory conditions.” Clin Pharmacol Ther: 2017 Sep [Epub ahead of print].

Full text of this article.

Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn’s disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here, we will review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases.

Menter, A., D. Thaci, J. J. Wu, W. Abramovits, F. Kerdel, D. Arikan, D. Guo, A. Ganguli, M. Bereswill, A. Camez and W. C. Valdecantos (2017). “Long-term safety and effectiveness of adalimumab for moderate to severe psoriasis: Results from 7-year interim analysis of the esprit registry.” Dermatol Ther (Heidelb): 2017 Aug [Epub ahead of print].

Full text of this article.

INTRODUCTION: ESPRIT (NCT00799877) is an ongoing 10-year international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab in routine clinical practice for adult patients with chronic plaque psoriasis. Herein, we report the long-term safety, effectiveness, and patient-reported outcomes (PROs) following adalimumab treatment over the first 7 years of the ESPRIT registry. METHODS: All treatment-emergent (All-TE) adverse events (AE) since the initial (first ever) dose of adalimumab were assessed. Physician Global Assessment (PGA) and PROs (PROs for US patients only) were evaluated during registry participation. RESULTS: As of 30 November 2015, 6051 patients in the ESPRIT registry were analyzed, representing 23,660.1 patient-years (PY) of overall adalimumab exposure. The incidence rates for All-TE serious AEs, serious infections, and malignancies were 4.4, 1.0, and 1.0 events per 100 PY (E/100PY), respectively. The standardized mortality ratio for TE deaths in the registry was 0.27 (95% CI 0.18-0.38). During the registry’s first 7 years, PGA “clear” or “minimal” was achieved by >50% of patients at each annual visit, and among US patients, the mean improvement from baseline in different PROs was maintained. CONCLUSION: No new safety signals were identified during the first 7 years of the registry, and safety was consistent with the known safety profile of adalimumab. The number of TE deaths was below the expected rate. During the registry’s first 7 years, most of the patients remained free of All-TE cardiovascular events, serious infections, and malignancy. As-observed effectiveness of adalimumab and improvements from baseline in PROs were maintained through 7 years of registry participation.

Kivelevitch, D., J. M. Schussler and A. Menter (2017). “Coronary plaque characterization in psoriasis.” Circulation 136(3): 277-280.

Full text of this article.

Psoriasis is strongly associated with multiple comorbidities, including obesity, tobacco smoking, diabetes mellitus, dyslipidemia, hypertension, and psychiatric, autoimmune, renal, and cardiovascular diseases, among others.5 Multiple publications have confirmed the association between psoriasis and vascular disease.5–8 Patients with psoriasis, especially those <50 years old and with more severe disease, are at higher risk of developing coronary artery disease (CAD).9 Furthermore, patients with moderate to severe psoriasis have a reduced life expectancy of ≈4 to 5 years relating to cardiovascular disease (CVD). Traditional risk assessment tools such as the Framingham risk score do not appropriately estimate this CAD risk. Recent studies that used both noninvasive and invasive coronary artery studies of patients with psoriasis and have shown a higher prevalence of CAD in patients with psoriasis compared with healthy individuals.10–13 Our recent coronary artery calcium score study of 129 patients with psoriasis with moderate to severe disease revealed a risk similar to that of patients with type II diabetes mellitus and significantly higher than that of healthy patients.10 One of the major areas of research and interest in the therapy of moderate to severe psoriasis is the potential benefit of systemic therapies such as methotrexate and biological therapies, especially tumor necrosis factor-α antagonist agents, on CAD.14