Journal of Clinical and Aesthetic Dermatology

Psoriasis and Cutaneous Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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U pdates on Psoriasis and Cutaneous Oncology: Proceedings from the 2016 MauiDerm Meeting [ S E P T E M B E R 2 0 1 6 • V O L U M E 9 • N U M B E R 9 ] S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y S 1 7 achieve ACR 20, ACRO 50, and PASI 75 scores. Thus, in PsA patients, the efficacy of methotrexate showed a slightly greater ACR-20 response in the TICOA trial versus the MIPA trial (41% vs. 34%), which suggests that methotrexate can have some efficacy for some PsA patients, although the extent of benefit was relatively low for most. In addition, there appears to be a dose reponse, with weekly doses of 15mg or higher being more effective. The availability of additional biologic agents has expanded therapeutic options in PsA care by adding a wealth of new weapons to the armamentarium (Figure 2). 115 At present, there are three main classes of biological agents proven effective in treating PsA: TNF-α inhibitors (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), agents that target IL-12 and/or IL-23 (ustekinumab, with others in development), and agents that target IL-17A (secukinumab, with others in development). 1 16 A meta-analysis of biologic agents for the treatment of PsA (assessing data from 12 randomized clinical trials) suggested that that patients treated with TNF inhibitors may have achieved higher levels of articular response than those treated with newer biologic agents, whereas the newer biologic agents, such as ustekinumab and secukinumab, may achieve higher levels of dermatologic response. However, there are issues that make comparisons of therapies not assessed head-to-head potentially tenuous. Also, in studies average responses for groups of patients are reported, whereas individual patients can have distinct results. Although TNF inhibitors have been available for the treatment for several years now, we continue to learn more about these agents. The recently published GO- REVEAL trial, a Phase 3, randomized, double-blind trial with placebo control through 24 weeks evaluated MDA outcomes in PsA patients treated with golimumab 50/100mg. 118 After 24 weeks, patients were followed by open-label extension up to five years. Golimumab treatment was associated with significantly higher rates of MDA responses versus placebo at Week 14 (23.5% vs. 1.09%, p<0.0001), Week 24 (28.1% vs. 7.7%, p<0.0001), and Week 52 (42.4% vs. 30.2%, p=0.037). About half of all patients in the golimumab group achieved MDA at least once during the study. Further, golimumab was associated with greater functional improvement, higher patient global assessments, and better radiographic outcomes than placebo. The relationship between trough serum concentrations of adalimumab and clinical response was explored in a 28-week study of 103 PsA patients. 119 Patients were treated with 40mg of subcutaneous adalimumab every two weeks with serum trough levels of the agent and clinical response (change over baseline) measured at 28 weeks. At the end of the study, the mean serum trough concentration was 7.2mg/L (range 0.0– 18.8), which falls within the presumed optimal range (5–8mg/L) based on work done in RA patients. About 35 percent of patients in the study had serum trough concentrations <5mg/L and 58 percent of these patients had antidrug antibodies (ADAb). About 47 percent had serum trough concentrations >8mg/L and some had low titer or intermittent ADAb. Thus, it appears that concentrations of 1.0mg/L and higher showed efficacy, whereas concentrations beyond 8mg/L did not confer additional benefits. A topic of increasing interest across many immunologic diseases treated with biologic agents is whether patients who achieve appropriate goals of therapy might be able to taper or even discontinue treatment. Factors that spur such interest include cost, consideration of potential adverse effects, and patient preferences. 120 There is a paucity of evidence from the literature to guide tapering strategies, so clinicians should be aware of the patient's history, have clear goals and how to measure them, reach an agreement with the patient about how to define failure (for example, return of disease activity), and determine how long the patient will be followed once the drug is tapered or discontinued. There is great interest in newer agents for PsA, including those that target IL-17. In a Phase 2 placebo- controlled study of 606 PsA patients randomized to receive IV secukinumab (10mg/kg) at Weeks 0, 2, and 4 followed by subcutaneous secukinumab (doses of either 75 or 150mg) every four weeks versus placebo. 121 At 24 weeks, secukinumab patients were significantly more likely to achieve an ACR20 rating (50.0% of 150mg and 50.5% of 75mg) versus placebo (17.3%, p<0.001 for both comparisons to placebo). Results were durable to 52 weeks although infections, including candida, were more frequent in secukinumab patients than placebo patients. These results confirm the efficacy of drugs targeting IL- Figure 2. Biologic agents and their targets in systemic inflammatory autoimmune diseases. Reprinted with permission: Her M, Kavanaugh A. Alterations in immune function with biologic therapies for autoimmune disease. J Allergy Clin Immunol. 2016;137(1):19–27.

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