Benefit-risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis.
BACKGROUND
Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis.


OBJECTIVE
To determine the benefit-risk balance of TNF antagonists in psoriasis.


METHODS
Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab. Integrated analyses that included open-label safety data from TNF-antagonist clinical trials were also conducted.


RESULTS
PASI 75 treatment effect data from the literature result in NNT values of 1·6 (95% confidence interval, CI 1·5-1·7) for adalimumab 40 mg every other week; 3·2 (95% CI 2·8-3·7) for etanercept 50 mg weekly or 25 mg twice weekly, and 2·3 (95% CI 2·1-2·5) for etanercept 50 mg twice weekly; and 1·4 (95% CI 1·3-1·5) for infliximab 5 mg kg(-1) dosing. For serious noninfectious, serious infectious and malignant adverse events, point estimates of the NNHs are generally at least two orders of magnitude larger than the NNTs, and the 95% CIs for the NNHs for adalimumab, etanercept and infliximab overlap. Analyses that included open-label data corroborated, with increased exposure to study agents, the low risk of adverse events observed in placebo-controlled periods.


CONCLUSIONS
These analyses demonstrated that, during the initial year of treatment, the likelihood of success with anti-TNF therapy for psoriasis was several orders of magnitude greater than the likelihood of serious toxicity.
Langley
R G
RG
Queen Elizabeth II Health Sciences Centre, Division of Dermatology, Department of Medicine, Dalhousie University, Halifax, NS B3H 2Y9, Canada. richard.langley@dal.ca
Strober
B E
BE
Gu
Y
Y
Rozzo
S J
SJ
Okun
M M
MM
D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D018570:Risk Assessment / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept