Membership NO : 3 Posts : 574 Join date : 2011-04-12
Subject: Adalimumab for Psoriasis: Making the Switch Tue May 31, 2011 4:19 pm
Adalimumab for Psoriasis: Making the Switch Switching to Adalimumab for Psoriasis Patients with Suboptimal Response to Etanercept, Methotrexate, or Phototherapy: Efficacy and Safety Results From an Open-Label Study
Strober BE, Poulin Y, Kerdel FA, et al J Am Acad Dermatol. 2011;64:671-681
Study Summary Background. Psoriasis is a chronic, potentially debilitating inflammatory skin disorder associated with erosive arthritis and an increased risk for cardiovascular disease.[1] Management strategies are tailored to disease severity, with milder psoriasis typically responding to topical therapy and moderate to severe disease requiring the addition of phototherapy and/or systemic immunosuppressive drugs. Over the past decade, tumor necrosis factor alpha (TNF-alpha) antagonists (infliximab, etanercept, adalimumab) have become the "go-to" drugs for controlling moderate to severe psoriasis. This drug class offers impressive, durable efficacy while minimizing the side effects seen with less selective immunosuppressive agents, such as methotrexate and cyclosporine. How should patients be transitioned to TNF-alpha blockers such as the monoclonal antibody adalimumab? Is it better to overlap treatments or simply stop current treatment, allow for a brief "washout" period, and then initiate the TNF-alpha blocker? If a patient is flaring on one TNF-alpha blocker (etanercept), would that patient potentially benefit from trying another drug in the same class, such as adalimumab? Methods. To address these important questions, Strober and coworkers conducted a multicenter, open-label trial looking at 152 patients (mean age: 47.6 years; 59.9% men; 87.5% white) with moderate to severe chronic plaque psoriasis (mean affected body surface area: 11.9%; mean Psoriasis Area Severity Index [PASI] score: 10.6; history of psoriatic arthritis : 46.7%) who had failed to respond adequately to either methotrexate (MTX), narrow-band ultraviolet-B (NB-UVB) phototherapy, or etanercept. This 16-week study contained 3 subgroups: suboptimal responders to etanercept (n = 82), MTX (n = 41), and NB-UVB (n = 29). Patients who had been taking etanercept discontinued this drug 11-17 days before starting adalimumab, corresponding to 3 half-lives of etanercept. The adalimumab loading dose was 80 mg at week 0, 40 mg at week 1, then 40 mg adalimumab every other week. The washout periods for MTX or NB-UVB ranged from 4 to 10 days. Patients could continue topical therapies during the adalimumab treatment phase, but no new topicals were allowed. Investigators judged treatment response using Physician Global Assessment (PGA) scores. Secondary outcome measures included: the PASI, Dermatology Life Quality Index (DLQI), and a visual analog scale (VAS) to rate pain-related plaque psoriasis and psoriatic arthritis. Results. After 16 weeks of adalimumab therapy, half of the patients (52%) in all subgroups had achieved PGA scores of "clear" or "minimal." Specifically, this level of improvement was reached in 49%, 61%, and 48% of patients who had failed to clear using, respectively, etanercept, MTX, or NB-UVB. Only 4 patients experienced flaring, defined as at least 125% worsening of their PASI scores compared with baseline (measured during screening). In addition:
Improvement in PGA scores was mirrored by all secondary efficacy variables.
Study patients experienced mean reductions in psoriasis and psoriatic arthritis pain scores, most markedly evident in those who had been using NB-UVB prior to adalimumab therapy.
No TNF-alpha-related severe adverse events were observed during the study period (eg, malignancies, opportunistic infections, tuberculosis, lupus-like syndrome, demyelinating disease), and no significant laboratory abnormalities were detected.
Serum levels of C-reactive protein -- a biomarker of systemic inflammation commonly elevated in psoriasis patients -- declined during adalimumab therapy. Theoretically, this may reduce the risk for cardiac disease such as myocardial infarction.[2]
Viewpoint In the study by Strober and coworkers, roughly 50% of patients who responded suboptimally to etanercept, MTX, or NB-UVB phototherapy still enjoyed dramatic clearance with adalimumab -- a result that bolsters data from the larger CHAMPION (Comparative Study of Humira vs Methotrexate vs Placebo in Psoriasis Patients) study.[3] Of note, all patients classified as treatment "failures" had been on their previous regimens for therapeutically appropriate periods of time using standard dosing (eg, at least 6 months of etanercept therapy, or at least 3 months with clinical deterioration of efficacy). It is intriguing that failure to clear with another TNF antagonist (etanercept) did not predict a lower likelihood of therapeutic success with adalimumab. This difference cannot be attributed to suboptimal etanercept dosing, because it was observed even in patients who had been taking 50 mg of etanercept twice weekly. Rather, these therapeutic differences likely stem from more fundamental, structural, and functional differences between the 2 drugs that should be further explored.[4]
In summary, Strober and colleagues have demonstrated that patients with moderate to severe psoriasis can be transitioned safely from NB-UVB, MTX or etanercept to adalimumab without overlapping treatments. Theoretically, this might reduce the risk for synergistic toxicities such as immunosuppression and future malignancy, but such potential benefits would best be shown through long-term follow-up data. Meanwhile, their results beg another question: Why not just start adalimumab immediately after discontinuing the previous treatment? Wouldn't this reduce the risk for even transient flaring? Is a washout period necessary?
References
Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis: a randomized, controlled phase III trial. JAMA. 2006;296:1735-1741. Abstract
Inoue N. Vascular C-reactive protein in the pathogenesis of coronary artery disease: role of vascular inflammation and oxidative stress. Cardiovasc Hematol Disord Drug Targets. 2006;6:227-231. Abstract
Saurat JH, Stingl G, Dubertret L, et al. CHAMPION Study Investigators. Efficacy and safety of adalimumab vs methotrexate vs placebo in psoriasis patients (CHAMPION). Br J Dermatol. 2008;158:558-566. Abstract
Kaymakcalan Z, Sakorafas P, Bose S, et al. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol. 2009;131:308-316. Abstract
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