Lead Investigator: Alexa Kimball, Beth Israel Deaconess Medical Center
Title of Proposal Research: Effects of adalimumab on inflammation-associated abnormal hematologic patterns in patients with Hidradenitis Suppurativa
Vivli Data Request: 7127
Funding Source: None
Potential Conflicts of Interest: I am a consultant and Investigator for Abbvie, Eli Lilly, Janssen, BMS, Novartis, Pfizer, UCB, Leo Pharma, Meiji Pharma, and Regeneron. Advisor to the Organization of Teratology Information Services (OTIS), Vimalan Biosciences. Fellowship funding from Janssen and Abbvie. Stockholder in Ventxy. Bioscience and Board of Directors, Almirall. BOD and Past President International Psoriasis Council. OTIS Pregnancy Registry Board Stelara, Cimzia and Otezla. These conflicts are regularly reviewed by my institution and managed via disclosure.
Summary of the Proposed Research:
Hidradenitis suppurativa (HS) is a painful and debilitating skin disease that can last for decades. Patients are affected by painful skin lumps and boils, primarily in the armpits and groin. These areas can get worse and form pockets of pus (abscesses), tunnels within the skin (fistulae), and extensive scarring. In addition to skin disease, HS patients may have abnormal blood tests, including anemia (low red blood cell counts; red blood cells carry oxygen) and elevated white blood cell counts (white blood cells fight infection so high counts can indicate infection). These abnormal blood tests can also include increases in blood markers of inflammation (when immune system cells are activated to fight infection of for some other reason) that may affect the whole body, including one called C-reactive protein (CRP). These health changes seem happen more often in people with worse skin disease suggesting that that they are related. While raised platelet levels (platelets help with clotting) have not yet been associated HS, elevated platelet levels can be seen in other diseases that also have significant inflammation.
The set of these blood test abnormalities and painful draining skin lesions can present a problem for physicians and lead to unintended consequences. A common instinct, when faced with an elevated white blood cell count and a patient who appears unwell, is to treat for infection, which for these patients, may be unnecessary. Anemia and high platelet levels can mimic blood cancer and also lead to unnecessary testing. In this work, we plan to study patients with blood abnormalities associated with HS to see if they improve with adalimumab, a medication proven to improve HS, compared to patients who receive placebo treatment.
Statistical Analysis Plan:
Our primary analysis will use a composite variable of patients who have 4 abnormalities with the most stringent outcome measure of resolution of all 4 into normal levels. The outcome of reversion to normal values in treated versus placebo groups will be tested in 5 additional analyses: the population with platelet abnormalities, the population with WBC abnormalities, the population with anemia (as defined by either low HgB or HCT) and patients with platelet abnormalities and anemia. Changes in MCV are exploratory and will be evaluated as an additional analysis.
Data will be presented as mean and standard deviation, median and interquartile range, or n (%), depending on data distribution.
independent data, comparisons will be made using Chi-square or Fisher’s exact tests for categorical variables and parametric or nonparametric tests for continuous variables, as appropriate. For paired data, comparisons will be made using McNemar’s test for categorical variables and parametric or non-parametric paired tests for continuous variables, as appropriate. Potential confounders will be assessed
using univariate analysis and considered for addition in the final model if they appreciably change the effect estimates or are deemed to be clinically relevant through a search of prior literature. Initial study participation will be included as a covariate in the regression models.
Sample size calculation:
Sample size calculations show we will need 22 patients in each group to show a difference of 40% returning to normal values (65% versus 25%) with an α=0.05 and power of 0.80. This success rate is based on a retrospective review of our patients with similar abnormal values that is currently under review for publication.
Adjustments for Source population and pooling of data:
As mentioned above, the Phase 3 trials have been reported on together previously. Baseline demographics and clinical characteristics will be compared between the Phase 3 and Phase 2 study populations for differences if Phase 2 is included. Any statistically or clinically meaningful
differences will be adjusted for in the final analysis. Sensitivity analyses will also be conducted to assess our primary association separately in the Phase 3 and Phase 2 study populations. Although we would expect our sample size could be insufficient for statistically significant findings in the separate populations, the effect sizes should be similar, which would allow for the presentation of pooled results. Given we are pooling two study populations, tests of heterogeneity and further statistical testing of heterogeneity between the samples would be underpowered.
A Phase 3 Multicenter Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa – PIONEER I
Data Contributor: AbbVie
Study ID: NCT01468207
Sponsor ID: M11-313
A Phase 3 Multicenter Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa – PIONEER II
Data Contributor: AbbVie
Study ID: NCT01468233
Sponsor ID: M11-810
A Phase 2 Multicenter Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Chronic Hidradenitis Suppurativa
Data Contributor: AbbVie
Study ID: NCT00918255
Sponsor ID: M10-467
Gunter S, Porter M, Gibson R, Kimball AB. 423 Baseline C-reactive protein correlates with adalimumab and placebo 3non-response in patients with hidradenitis suppurativa. Journal of Investigative Dermatology. 2023 May 1;143(5):S73. https://www.jidonline.org/article/S0022-202X(23)00604-8/pdf