Title of Proposal Research: Predictors of Treatment Response, Adverse Events, Changes in Anaemia status and Assessment of Lesion Count Variability in Hidradenitis Suppurativa.
Vivli Data Request: 4117
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Hidradenitis Suppurativa (HS) is a chronic inflammatory disease affecting between 1%-4% of the general population. It has a propensity to affect women and causes painful, chronically draining abscesses, nodules and tunnels in the axillae, groin and other flexural areas. There is a limited understanding of the disease, particularly factors that influence successful (or unsuccessful) treatment of the disease with current therapies.
Our project contains a number of sub-studies which will aim to further investigate contributing factors associated with Adalimumab (Humira) therapy, as well as factors related to assessment of disease, which plays an important role in how the disease is assessed in future clinical trials.
These separate projects are all of high interest to clinicians treating Hidradenitis Suppurativa (HS) as well as researchers investigating the disease. The separate projects are as follows:
1) Rates of Malignancy and Serious Infections in Hidradenitis Suppurativa Patients Treated with Adalimumab
2) Predictors of Loss of Treatment Response in Patients with Hidradenitis Suppurativa treated with Adalimumab
3) The effect of Body weight upon clinical response rates in patients with Hidradenitis Suppurativa treated with Adalimumab
4) The effect of Adalimumab therapy in Hidradenitis Suppurativa upon anemia of chronic disease
5) Assessing the normal variability of lesion counts and disease activity in Hidradenitis Suppurativa.
Each of these 5 sub-studies addresses important, as yet poorly defined aspects of the disease and treatment with Adalimumab. Increasing our knowledge in these areas will help optimize treatment outcomes for patients, understand the effect of treatment upon patient outcomes and increase patient compliance, satisfaction and quality of life.
Statistical Analysis Plan:
The selected studies were chosen as they represent the highest level of evidence (Phase 3 clinical trial data) pertaining to Adalimumab therapy in HS. The open label extension study is the largest collection of longitudinal data of high quality available in the literature.
We will proceed by examining the distributional qualities of all measures, identifying outliers, attending to transformations needed to satisfy analytic assumptions, and examine and resolve any missing data issues through the implementation of various imputations methods as needed.
Depending upon distributional properties of the outcome measure of interest, we will initially compute means, standard deviations, minimum and maximums (for continuous measures), or sample sizes and proportion of responses (for categorical and count measures), both overall and by group (i.e. Adalimumab vs control), for baseline and follow-up time points. Group differences and baseline, and at follow-up, will be tested using t-tests (or non-parametric equivalent) and chi-squared tests.
We will then proceed to compute the observed treatment effects by regressing the Week 12 outcome variable on the primary independent dummy variable for treatment (i.e. 1= Adalimumab, 0=Control) along with the baseline value of the outcome serving as the sole covariate, using either OLS, Logistic, or Poisson regression (for Continuous, binary, or count data, respectively). We will then adjust these observed measures (i.e. mean differences, Odds Ratio’s or differences in counts) by identified additional covariates (e.g. Gender, Race, Age), and then explore the moderation effects by examining the difference in effects under stratified analyses, and interaction models in regression to test for significance of any observed moderation effects.
A Phase 3, Open-Label Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa – PIONEER (Open-Label Extension)
Study ID: NCT01635764
Sponsor ID: M12-555
Study ID: NCT01468233
Sponsor ID: M11-810
Study ID: NCT01468207
Sponsor ID: M11-313
Frew, J., Jiang, C., Singh, N., Grand, D., Navrazhina, K., Vaughan, R. and Krueger, J. (2020), Malignancy and Infection Risk During Adalimumab Therapy in Hidradenitis Suppurativa. Clin Exp Dermatol. Accepted Author Manuscript. doi: 10.1111/ced.14264