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 Adalimumab for Psoriasis: Making the Switch

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PostSubject: Adalimumab for Psoriasis: Making the Switch   Tue May 31, 2011 4:19 pm

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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:

  1. Improvement in PGA scores was mirrored by all secondary efficacy variables.
  2. 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.
  3. 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.
  4. 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

  1. 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
  2. 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
  3. 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
  4. 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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