Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab

Simon J Gunter; Zachary E Holcomb; Barbara D Lam; Martina L Porter; Alexa B Kimball

doi:10.1001/jamadermatol.2024.1075

. 2024 May 8;160(6):678–681. doi: 10.1001/jamadermatol.2024.1075

Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab

Simon J Gunter ¹, Zachary E Holcomb ², Barbara D Lam ³, Martina L Porter ^4,⁵, Alexa B Kimball ^4,^5,^✉

¹Harvard Medical School, Boston, Massachusetts

²Section of Dermatology, Department of Medicine, Carilion Clinic, Roanoke, Virginia

³Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

⁴Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts

⁵Department of Dermatology, Harvard Medical School, Boston, Massachusetts

Accepted for Publication: March 12, 2024.

Published Online: May 8, 2024. doi:10.1001/jamadermatol.2024.1075

^✉

Corresponding Author: Alexa Kimball, MD, MPH, Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (clears@bidmc.harvard.edu).

Author Contributions: Mr Gunter and Dr Kimball had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Holcomb, Porter, Kimball.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gunter, Holcomb, Lam.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Gunter, Holcomb.

Administrative, technical, or material support: Kimball.

Supervision: Holcomb, Lam, Porter, Kimball.

Conflict of Interest Disclosures: Mr Gunter reported personal fees from Merck outside the submitted work. Dr Porter reported personal fees and grants from AbbVie during the conduct of the study; personal fees and grants from Novartis, Pfizer, Incyte, Sonoma Biotherapeutics, Moonlake, UCB, Sonoma, Eli Lilly, and Sanofi, grants from Bristol Meyers Squibb, Prometheus Laboratories, Bayer, and Anaptys Bio; personal fees from Alumis, Trifecta Clinical, and Janssen, grants from Anaptys Bio, Aristea, and Janssen outside the submitted work. Dr Kimball reported personal fees from AbbVie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, Priovant, Sanofi, Sonoma Bio, Target RWE, Union, and grants from AbbVie, Admirx, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, Prometheus, Sanofi, Sonoma Biotherapeutics, and UCB outside the submitted work and being on the board of directors of Almirall. No other disclosures were reported.

Funding/Support: This article is based on research using data from AbbVie, which has been made available through Vivli, Inc. This work was conducted with support from the UM1TR004408 award through Harvard Catalyst Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) and financial contributions from Harvard University and its affiliated academic health care centers.

Role of the Funder/Sponsor: AbbVie reviewed this article for confidential information before its submission. The funder/sponsor of the original PIONEER studies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University, and its affiliated academic health care centers, or the National Institutes of Health. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.

Data Sharing Statement: See Supplement 2.

^✉

Corresponding author.

PMCID: PMC11079783 PMID: 38717768

Abstract

This post hoc analysis of PIONEER I and II randomized clinical trials assesses whether receiving adalimumab is associated with decreased hematologic abnormalities and increased clinical improvement in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is an inflammatory skin disorder that is characterized by nodules, abscesses, and sinus tracts.¹ Substantial inflammatory burden, anemia, and leukocytosis have been frequently reported in patients with HS.^2,3 We previously reported that anemia, leukocytosis, or thrombocytosis improved after immunomodulatory therapy in a small cohort of patients with HS.⁴ Herein, we further investigate hematologic abnormalities in patients with HS to determine whether they improved with HS-directed therapy.

Methods

This post hoc analysis included the PIONEER I and II randomized clinical trials, which were similarly designed, phase 3 trials of adalimumab treatment for patients with HS.⁵ Patients with moderate-to-severe HS were randomized to either 40-mg adalimumab weekly or placebo for the first 12 weeks of the study, defined as period 1 (Supplement 1). Clinical improvement at week 12 was assessed using Hidradenitis Suppurativa Clinical Response (HiSCR). We limited this analysis to period 1. The 4 groups were defined based on treatment assignment and HiSCR status: adalimumab responders, adalimumab nonresponders, placebo responders, and placebo nonresponders. We hypothesized that receiving adalimumab was associated with decreased hematologic abnormalities and increased clinical improvement. Two-sided hypothesis testing was performed using paired t tests, factorial analyses of variance, and χ² tests. Significance was determined with α < .05. Pairwise comparisons were conducted using Tukey tests and pairwise proportion tests. The Beth Israel Deaconess Medical Center Committee on Clinical Investigation deemed this study exempt from review and informed consent because it did not constitute human participant research. Data analysis was performed using R Studio statistical software, version 1.4.1717 (R Project for Statistical Computing).⁶

Results

The trials enrolled 633 patients, and 596 completed period 1 of each study. Among 594 patients with laboratory data available at baseline, 252 patients (42.4%) had at least 1 hematologic abnormality (defined as anemia, thrombocytosis, or leukocytosis) at baseline. Of these patients, 172 patients (68.3%) had 1 hematologic abnormality with 154 (61.1%) having anemia.

Baseline hemoglobin levels, white blood cell (WBC) count, and platelet count test results were similar between the groups (Table 1). Adalimumab recipients had significant improvements in hemoglobin levels (mean [SD], 0.37 [1.06] g/dL; P < .001), platelet count (−34.6 [68.3] ×10³/μL; P < .001), and WBC count (−1152.66 [2100.92] /μL; P < .001) (Table 2). Placebo recipients did not have significant improvements in these variables. A significant association was found between receiving adalimumab and the degree of improvement in hemoglobin levels (0.24 [95% CI, 0.12-0.37 g/dL]; P < .001), platelet count (−14.7 ×10³/μL [95% CI, −22.8 to −6.66 ×10³/μL], P < .001), and WBC count (−392.70 /μL, [95% CI, −693.48 to −91.92 /μL]; P = .01).

Table 1. Demographics and Clinical Characteristics of Patients Who Completed Period 1 and Had at Least 1 Hematologic Abnormality at Baseline.

Characteristic	Patients, No. (%)
Characteristic	Adalimumab responder (n = 49)	Adalimumab nonresponder (n = 74)	Placebo responder (n = 30)	Placebo nonresponder (n = 99)
Abnormalities
1	34 (69.4)	42 (56.8)	25 (83.3)	71 (71.7)
2	11 (22.4)	20 (27.0)	5 (16.7)	18 (18.2)
3	4 (8.2)	12 (16.2)	0	10 (10.1)
Age, y
<40	28 (57.1)	51 (68.9)	19 (63.3)	56 (56.6)
40-60	20 (40.8)	23 (31.1)	11 (36.7)	41 (41.4)
≥65	1 (2.0)	0	0	2 (2.0)
BMI
<25	13 (26.5)	11 (14.9)	3 (10.0)	9 (9.1)
25-34.9	21 (42.9)	34 (45.9)	15 (50.0)	46 (46.5)
≥35	15 (30.6)	28 (37.8)	11 (36.7)	44 (44.4)
NR	0	1 (1.4)	1 (3.3)	0
Sex
Female	26 (53.1)	38 (51.4)	22 (73.3)	63 (63.6)
Male	23 (46.9)	36 (48.6)	8 (26.7)	36 (36.4)
Race^a
Asian	1 (2.0)	1 (1.4)	0	4 (4.0)
Black	9 (18.4)	16 (21.6)	7 (23.3)	23 (23.2)
White	38 (77.6)	55 (74.3)	23 (76.7)	69 (69.7)
Other^b	1 (2.0)	2 (2.7)	0	3 (3.0)
Hurley stage
II	20 (40.8)	27 (36.5)	14 (46.7)	32 (32.3)
III	29 (59.2)	47 (63.5)	16 (53.3)	67 (67.7)
Abscess and inflammatory nodules
≤5	9 (18.4)	12 (16.2)	8 (26.7)	26 (26.3)
6-10	13 (26.5)	25 (33.8)	10 (33.3)	23 (23.2)
≥11	27 (55.1)	37 (50.0)	12 (40.0)	50 (50.5)
Inflammatory markers, mean (SD)
Hemoglobin, g/dL	12.7 (1.8)	12.6 (1.7)	12.5 (1.6)	12.4 (1.8)
Platelets, ×10³/μL	320.0 (89.3)	353.0 (103.0)	299.0 (77.1)	325.0 (100.0)
WBC count, /μL	10 822.4 (3 574.8)	11 174.3 (2548.2)	10 176.7 (2794.9)	11 081.8 (3177.9)

Open in a new tab

To convert hemoglobin from g/dL to g/L, multiply by 10; platelet count from ×10³/μL to ×10⁹/L, multiply by 1; WBC count from /µL to ×10⁹/L, multiply by 0.001.

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); NR, not reported; WBC, white blood cell.

^{^a}

Race and ethnicity were self-reported. The incidence of patients with hidradenitis suppurativa differs by race and ethnicity, and a clinical trial population (as seen here) may not always reflect a population's true racial and ethnic distribution of disease.

^{^b}

Other indicates American Indian, Alaska Native, and other on self-report.

Table 2. Mean Change in Laboratory Values in Patients With at Least 1 Hematologic Abnormality at Baseline by Treatment or Response.

Group	Mean change (SD)^a	P value
Adalimumab (n = 123)
Hemoglobin, g/dL^b	0.37 (1.06)	<.001^c
Platelet count, ×10³/μL^d	−34.60 (68.30)	<.001^c
WBC count, /μL^d	−1152.66 (2100.92)	<.001^c
Placebo (n = 129)
Hemoglobin, g/dL^b	−0.07 (0.70)	.26
Platelet count, ×10³/μL^d	−2.52 (45.40)	.54
WBC count, /μL^d	−319.35 (2176.28)	.10
Responders (n = 79)
Hemoglobin, g/dL^b	0.44 (1.02)	<.001^c
Platelet count, ×10³/μL^d	−31.50 (61.50)	<.001^c
WBC count, /μL^d	−1249.54 (2179.04)	<.001^c
Nonresponders (n = 173)
Hemoglobin, g/dL^b	0.02 (0.84)	.79
Platelet count, ×10³/μL^d	−12.40 (58.30)	.006^c
WBC count, /μL^d	−509.94 (2142.69)	.002^c
Adalimumab responder (n = 49)
Hemoglobin, g/dL^b	0.72 (1.03)	<.001^c
Platelet count, ×10³/μL^d	−42.20 (70.30)	<.001^c
WBC count, /μL^d	−1572.34 (2201.06)	<.001^c
Adalimumab nonresponder (n = 74)
Hemoglobin, g/dL^b	0.15 (1.03)	.20
Platelet count, ×10³/μL^d	−29.80 (67.00)	<.001^c
WBC count, /μL^d	−885.14 (2044.22)	<.001^c
Placebo responder (n = 30)
Hemoglobin, g/dL^b	−0.01 (0.84)	.93
Platelet count, ×10³/μL^d	−13.70 (37.70)	.07
WBC count, /μL^d	−662.96 (2052.98)	.11
Placebo nonresponder (n = 99)
Hemoglobin, g/dL^b	−0.08 (0.65)	.19
Platelet count, ×10³/μL^d	0.70 (47.10)	.88
WBC count, /μL^d	−223.71 (2210.05)	.32

Open in a new tab

To convert hemoglobin from g/dL to g/L, multiply by 10; platelet count from ×10³/μL to ×10⁹/L, multiply by 1; WBC count from /µL to ×10⁹/L, multiply by 0.001.

Abbreviation: WBC, white blood cell.

^{^a}

Calculated as the week 12 value minus the baseline value.

^{^b}

Six patients did not have laboratory values at week 12.

^{^c}

Statistically significant, determined using a 2-sided paired t test (α < .05).

^{^d}

Seven patients did not have laboratory values at week 12.

Adalimumab responders had significant improvements in hemoglobin levels (mean [SD], 0.72 [1.03] g/dL; P < .001), platelet count (−42.2 [70.3] ×10³/μL; P < .001), and WBC count (−1572.34 [2201.06] /μL; P < .001). Adalimumab clinical response was associated with the degree of improvement in hemoglobin levels (0.12 g/dL [95% CI, 0.00-0.24] g/dL; P = .05) that bordered significance.

Finally, rates of hematologic abnormality resolution differed between the 4 groups. Adalimumab responders were more likely to have a resolution of their anemia (16/30 [53.3%]) when compared with adalimumab nonresponders (10/48 [20.8%]; adjusted P = .04) and placebo nonresponders (10/60 [16.7%]; adjusted P = .004).

Discussion

In this post hoc analysis of 2 randomized clinical trials, we found that adalimumab, regardless of HiSCR responder status, was associated with improvements in common hematologic abnormalities. Patients with hematologic abnormalities at baseline and clinical response with adalimumab treatment exhibited greater improvements in their hematologic abnormalities and were more likely to have a resolution of their anemia relative to both adalimumab and placebo nonresponders. Although limited by sample size, we found no significant difference in the rate of hematologic abnormality resolution between placebo responders and adalimumab responders, consistent with clinical assessments suggesting that placebo responders may improve spontaneously. These findings highlight the high inflammatory load in patients with HS and the frequent occurrence of inflammation-related dyscrasias, which may warrant aggressive management. Further research is required to validate the generalizability of these results given the demographics of the PIONEER trials and racial and ethnic differences in reference intervals for hematologic markers.

Supplement 1.

eFigure. CONSORT Flow Diagram

jamadermatol-e241075-s001.pdf^{(156.6KB, pdf)}

Supplement 2.

Data Sharing Statement

jamadermatol-e241075-s002.pdf^{(15.5KB, pdf)}

References

1.Kurzen H, Kurokawa I, Jemec GB, et al. What causes hidradenitis suppurativa. Exp Dermatol. 2008;17(5):455-456. doi: 10.1111/j.1600-0625.2008.00712_1.x [DOI] [PubMed] [Google Scholar]
2.Miller IM, Ring HC, Prens EP, et al. Leukocyte profile in peripheral blood and neutrophil-lymphocyte ratio in hidradenitis suppurativa: a comparative cross-sectional study of 462 cases. Dermatology. 2016;232(4):511-519. doi: 10.1159/000446021 [DOI] [PubMed] [Google Scholar]
3.Parameswaran A, Garshick MS, Revankar R, Lu CP, Chiu ES, Sicco KIL. Hidradenitis suppurativa is associated with iron deficiency anemia, anemia of chronic disease, and sickle cell anemia—a single-center retrospective cohort study. Int J Womens Dermatol. 2021;7(5Part B):675-676. doi: 10.1016/j.ijwd.2021.07.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Morss-Walton PC, Greif C, Holcomb ZE, et al. Treatment of hidradenitis suppurativa resolves associated hematologic abnormalities. Int J Womens Dermatol. 2022;8(1):e011. doi: 10.1097/JW9.0000000000000011 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5):422-434. doi: 10.1056/NEJMoa1504370 [DOI] [PubMed] [Google Scholar]
6.RStudio Team . RStudio: integrated development environment for R. 2022. Accessed April 3, 2024. https://www.rstudio.com/

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eFigure. CONSORT Flow Diagram

jamadermatol-e241075-s001.pdf^{(156.6KB, pdf)}

Supplement 2.

Data Sharing Statement

jamadermatol-e241075-s002.pdf^{(15.5KB, pdf)}

[dld240007r1] 1.Kurzen H, Kurokawa I, Jemec GB, et al. What causes hidradenitis suppurativa. Exp Dermatol. 2008;17(5):455-456. doi: 10.1111/j.1600-0625.2008.00712_1.x [DOI] [PubMed] [Google Scholar]

[dld240007r2] 2.Miller IM, Ring HC, Prens EP, et al. Leukocyte profile in peripheral blood and neutrophil-lymphocyte ratio in hidradenitis suppurativa: a comparative cross-sectional study of 462 cases. Dermatology. 2016;232(4):511-519. doi: 10.1159/000446021 [DOI] [PubMed] [Google Scholar]

[dld240007r3] 3.Parameswaran A, Garshick MS, Revankar R, Lu CP, Chiu ES, Sicco KIL. Hidradenitis suppurativa is associated with iron deficiency anemia, anemia of chronic disease, and sickle cell anemia—a single-center retrospective cohort study. Int J Womens Dermatol. 2021;7(5Part B):675-676. doi: 10.1016/j.ijwd.2021.07.008 [DOI] [PMC free article] [PubMed] [Google Scholar]

[dld240007r4] 4.Morss-Walton PC, Greif C, Holcomb ZE, et al. Treatment of hidradenitis suppurativa resolves associated hematologic abnormalities. Int J Womens Dermatol. 2022;8(1):e011. doi: 10.1097/JW9.0000000000000011 [DOI] [PMC free article] [PubMed] [Google Scholar]

[dld240007r5] 5.Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5):422-434. doi: 10.1056/NEJMoa1504370 [DOI] [PubMed] [Google Scholar]

[dld240007r6] 6.RStudio Team . RStudio: integrated development environment for R. 2022. Accessed April 3, 2024. https://www.rstudio.com/

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Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab

Simon J Gunter, MPhil

Zachary E Holcomb, MD

Barbara D Lam, MD

Martina L Porter, MD

Alexa B Kimball, MD, MPH

Abstract

Methods

Results

Table 1. Demographics and Clinical Characteristics of Patients Who Completed Period 1 and Had at Least 1 Hematologic Abnormality at Baseline.

Table 2. Mean Change in Laboratory Values in Patients With at Least 1 Hematologic Abnormality at Baseline by Treatment or Response.

Discussion

References

Associated Data

Supplementary Materials

ACTIONS

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PERMALINK

Hematologic Abnormalities in Patients With Hidradenitis Suppurativa Receiving Adalimumab

Simon J Gunter, MPhil

Zachary E Holcomb, MD

Barbara D Lam, MD

Martina L Porter, MD

Alexa B Kimball, MD, MPH

Abstract

Methods

Results

Table 1. Demographics and Clinical Characteristics of Patients Who Completed Period 1 and Had at Least 1 Hematologic Abnormality at Baseline.

Table 2. Mean Change in Laboratory Values in Patients With at Least 1 Hematologic Abnormality at Baseline by Treatment or Response.

Discussion

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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