Onset of Action of Biologics in Patients With Moderate-to-Severe Psoriasis
March 2018 | Volume 17 | Issue 3 | Original Article | 247 | Copyright © March 2018
Kim A. Papp MD PhDa and Mark G. Lebwohl MDb
aK Papp Clinical Research and Probity Medical Research, Waterloo, ONT, Canada bIcahn School of Medicine at Mount Sinai, New York, NY
BACKGROUND: The advent of biologics has improved patient outcomes in the treatment of moderate-to-severe psoriasis. The time it takes for patients to see clinically meaningful improvement is an important aspect of disease management.
OBJECTiIVE: To review the clinical data on the use of biologics in moderate-to-severe psoriasis, identifying which biologics may offer the quickest results.
METHODS: A review of the published and presented efficacy data on adalimumab, infliximab, ustekinumab, etanercept, brodalumab, ixekizumab, and secukinumab to estimate the time to achieve clinically meaningful outcome; defined as time for 25% of patients to achieve Psoriasis Area and Severity Index (PASI) 75, or a 50% reduction in mean baseline PASI.
RESULTS: Clinically meaningful outcomes were achieved within 2-11 weeks with biologics. Calculated times for 25% of patients to achieve PASI 75 were 2.1 [95% CI 2.0-2.3] weeks (brodalumab), 2.4 weeks (ixekizumab), 3.0 weeks (high-dose secukinumab), 3.5 weeks (infliximab), 4.6 weeks (adalimumab and high-dose ustekinumab), 5.1 weeks (low-dose ustekinumab), 6.6 weeks (high-dose entanercept), and 9.5 weeks (low-dose entanercept). Calculated times for 50% reduction in baseline PASI were 1.8 [95% CI 1.7-1.9] weeks (brodalumab), 1.9 weeks (ixekizumab), 3.0 [95% CI 2.8-3.2] weeks (high-dose secukinumab), 3.5 weeks (adalimumab), 3.7 weeks (infliximab), 5.1 weeks (low-dose ustekinumab), 6.5 weeks (high-dose entanercept), and 10.9 weeks (low-dose entanercept).
CONCLUSIONS: Brodalumab may have the most rapid onset of action of any biologic therapy used in psoriasis. Similar results were seen with both outcome measures and will have important implications in psoriasis management.
J Drugs Dermatol. 2018;17(3):247-250.
The significant reduction in quality of life and psychosocial disability suffered by psoriasis patients highlight the need for prompt, effective, and long-term disease control. The time taken for psoriasis patients to achieve a clinically relevant improvement in their disease is an important aspect of patient management and education, especially in very acute or severe forms,1 and has been shown to be very important to psoriasis patients.2 Along with efficacy, rapid disease improvement has been rated as the most important treatment goal by almost 95% of patients with moderate-to-severe psoriasis.3 The advent of biologic therapies has provided greatly improved treatment outcomes. However, data on how quickly these treatments become effective are sparse. We aim to review the current literature to determine the time needed for specific biologic treatments to achieve a given treatment goal, and discuss some of the limitations that exist within the data.
Limitations in Approach
Onset of action has not been a primary or secondary endpoint in any clinical trial. Calculations have been derived from linear interpolation between different time points or Kaplan-Meier approximations, whereby predicted mean or median times often lie between two study visits limiting the precision of any estimate. With some biologics, data are available from more than one study and onset of action has been calculated as a weighted mean taking into account the number of patients in the individual studies.4 However, it is not possible to remove bias that may have arisen due to different study quality because of their limited numbers. Different body regions may provide differing responses, with the head/neck and trunk being shown to respond quicker than psoriasis of the arms and legs;5,6 and both ethnic and regional differences have been reported.7,8 In addition, some important data were not publicly available to fully appreciate the impact of any concomitant medication, washout phases, or baseline disease severity. For example, a very high initial Psoriasis Area and Severity Index (PASI) may allow for a more significant and faster reduction in severity over the first few weeks. Where baseline PASI data are available these are indicated in our review.
Determining Onset of Action
A large number of clinical measures of psoriasis (in excess of 50) are used in clinical trials and daily practice.9 The PASI is the most commonly used clinical measure in research, evaluating