Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa

Hazel Lacson, Mercer University College of Pharmacy

 

Hidradenitis suppurativa (HS) is defined as a disease of the skin that begins as pimple-like bumps, usually manifesting in the underarms and groin area. Hidradenitis suppurativa is more commonly referred to as acne inversa.1 According to a review on the pathogenesis and treatment of HS, this condition is suggested to be more prominent in patients of African descent. 2

Risk factors of HS include smoking and obesity. Additionally, its main symptom is reported to be a hot or throbbing pain in the affected area. Treatment options for HS consist of three levels of management. Topical formulations are suggested to be used as a first line option. Should these not be effective, systemic options are recommended as next line therapy. Finally, surgical methods, such as laser therapy, are suggested as a last line of treatment for HS.2

Humira® (adalimumab) is a tumor necrosis factor (TNF) alpha blocker, inhibiting the inflammatory effects of TNF-alpha.3 Adalimumab’s (ADA’s) current indication through the Food and Drug Administration (FDA) is for patients with moderate to severe cases of rheumatoid arthritis.4 However, as of September 2015, ADA became the first and only FDA-approved treatment of HS.3 The following trial is reported to be the study that helped ADA gain FDA approval for use in HS.4

 

Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa5
Design Two phase 3, double-blind, placebo-controlled, multicenter trials; N= 633
Objective To observe the effectiveness of ADA in patients with HS
Study Groups PIONEER I: placebo group (n= 154) and ADA group (n= 153)

PIONEER II: placebo group (n= 163) and ADA group (n= 163)

Methods In period one, patients were randomly assigned to 40 mg of ADA weekly or matching placebo for 12 weeks. All patients who received ADA in period one and continued to period two underwent a second randomization at week 12. These patients were reassigned to ADA weekly (in PIONEER I) or to placebo (in PIONEER II) in a blinded fashion, and received that regimen for 24 weeks.
Duration 36 weeks
Primary Outcome Measure Clinical response (at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts) at week 12

 

Baseline Characteristics PIONEER I (n= 307) PIONEER II (n= 326)
Placebo (n= 154) ADA (n= 153) Placebo (n= 163) ADA (n= 163)
Female – no. (%) 105 (68.2) 91 (59.5) 113 (69.3) 108 (66.3)
Mean age – years 37.8 36.2 36.1 34.9
Race – no. (%) White 118 (76.6) 116 (75.8) 130 (79.8) 143 (87.7)
Black 29 (18.8) 33 (21.6) 20 (12.3) 9 (5.5)
Other 7 (4.5) 4 (2.6) 13 (8) 11 (6.7)
Previous systemic treatment – no. (%) 63 (40.1) 71 (46.4) 76 (46.6) 82 (50.3)
Prior surgery for hidradenitis suppurativa – no. (%) 13 (8.4) 21 (13.7) 18 (11) 27 (16.6)
Results Clinical response achieved:
PIONEER I (n= 307) PIONEER II (n= 326)
ADA (%) 41.8% 58.9%
Placebo (%) 26% 27.6%
P-value 0.003 <0.001
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: Not mentioned
Percentage that Discontinued due to Adverse Events:
Placebo ADA
PIONEER I 1.3% 0%
PIONEER II 3.7% 2.5%
Study Author Conclusions Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks.

 

The PIONEER I and PIONEER II trials have provided HS patients their first FDA-approved treatment, however there are still some areas of concern. A retrospective analysis reports that this disease is more prevalent in African-Americans.6 The PIONEER I and II trials included 101 sites that were spread over 14 countries, providing the resources necessary for a diverse study sample. Despite this, African-American patients only consisted of, at the most, one-fifth of an individual study group.5 Furthermore, a study on HS management in the United States reports that 74% of HS patients are treated with medication, as opposed to a medical procedure (11%).7   Based on this data, further studies should be made to explore the effects of ADA in African American patients.

 

References

  1. American Academy of Dermatology. https://www.aad.org/public/diseases/painful-skin-joints/hidradenitis-suppurativa#overview. Accessed August 24, 2016.
  2. Wollina U, Koch A, Heinig B, Kittner T, Nowak A. Acne inversa (Hidradenitis suppurativa): A review with a focus on pathogenesis and treatment. Indian Dermatol Online J. 2013;4(1):2-11.
  3. HUMIRA® [package insert] North Chicago, IL: Abbvie, Inc.; 2016.
  4. S. Food and Drug Administration. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080610.htm. Accessed August 31, 2016.
  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):422-34.
  6. Vlassova N, Kuhn D, Okoye GA. Hidradenitis suppurativa disproportionately affects African Americans: a single-center retrospective analysis. Acta Derm Venereol. 2015;95(8):990-1.
  7. Davis SA, Lin HC, Balkrishnan R, Feldman SR. Hidradenitis Suppurativa Management in the United States: An Analysis of the National Ambulatory Medical Care Survey and MarketScan Medicaid Databases. Skin Appendage Disord. 2015;1(2):65-73.

 

 

 

 

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