Continuous Weekly Adalimumab is the Optimal Long-term Strategy for Patients with Moderate-to-Severe  
Hidradenitis Suppurativa: Results from the PIONEER Open Label Extension Trial
Alexa B Kimball,1 Martin M Okun,2 Gerit Mulder3
1Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, Boston, MA, USA; 2Fort Healthcare, Fort Atkinson, WI, USA; 3AbbVie Inc, North Chicago, IL, USA

INTRODUCTION

1. Kimball A, et al. N Engl J Med. 2016;375:5.

• Determine the effectiveness of retreatment with ADAew in patients with 
moderate-to-severe HS, following dose withdrawal or reduction. 

• The optimal long-term strategy for managing HS patients with adalimumab 
appeared to be continuous weekly dosing, as either a short-term reduction 
of dose to every-other-week or treatment withdrawal (placebo) was 
associated with modest loss of long-term response. 

• This conclusion is limited by the small number of evaluable patients in this 
analysis.

• No new safety risks were identified.

• Adalimumab (originator) 40 mg weekly dosing (ADAew) is approved for 
treatment of moderate-to-severe hidradenitis suppurativa (HS).

• There are clinical circumstances where patients are obliged to temporarily 
discontinue or reduce this dose. 

• This is a pooled analysis of 3 trials that evaluated 40 mg ADAew in patients with 
moderate-to-severe HS:

 – The phase-3 placebo-controlled PIONEER I & II trials evaluated the efficacy 
and safety of ADAew vs placebo.1

 – The subsequent open-label extension trial (OLE) (NCT01635764) determined 
the long-term safety and efficacy of ADAew.

• In PIONEER I & II, patients randomized to 40 mg ADAew in the 12-week Period 
A were re-randomized at week 12 to 40 mg ADAew, 40 mg ADA every-other-
week (eow), or placebo for 24 weeks (Period B) (Figure 1). 

• At week 36 of the trial (week 24 of Period B), patients had the option to enter 
the OLE and receive 40 mg ADAew. Patients who discontinued during Period B 
due to loss of treatment response or lack/worsening of disease improvement 
could also enter the OLE at discontinuation. 

Figure 1. Study Schematic of PIONEER I and II, and the OLE

Randomization 1:1

Screening

Period A

Double-blind Placebo-controlled

12 weeks

Period B

0 12 16 36Week:

ADA 40 mg weekly 

Placebo

ADA 40 mg every-other-week 

Placebo

PIONEER I: ADA 40 mg weekly 

PIONEER II: Placebo

Open-Label 

Extension (OLE)

At least 60 weeks

ADA 40 mg 

weekly,

open-label 

ADA 40 mg weekly 

Double-blind Placebo-controlled

24 weeks

Randomization: stratified by baseline Hurley Stage II vs III (PIONEER I & II) & baseline concomitant antibiotic use (PIONEER II). Re-randomization 
for Period A ADA patients: stratified by week 12 HiSCR status at entry into Period B, & by baseline Hurley Stage II vs III. Period A: patients started 
ADA at week 4 after 160 mg (week 0), 80 mg (week 2). Patients receiving placebo in Period A, and ADA or placebo in Period B, were not included 
in this analysis.
Abbreviations: ADA=adalimumab; HiSCR=Hidradenitis Suppurativa Clinical Response.

Table 1. PIONEER I and II Key Eligibility/Exclusion Criteria
Inclusion Exclusion
• Adults, anti-TNFα-naïve, diagnosed with HS for ≥1 year 

prior to baseline
• No prior treatment with anti-TNF agents

• Inadequate response to oral antibiotics for the treatment 
of HS

• No other active skin disease that could interfere 
with assessment of HS

• Total abscess and inflammatory nodule (AN) count of ≥3 • Draining fistula count of >20 at baseline
• HS lesions in ≥2 body areas, one of which was Hurley 

Stage II or III

• The primary outcome measure was HiSCR (Hidradenitis Suppurativa Clinical 
Response) defined as a ≥50% reduction in total abscess and inflammatory 
nodule (AN) count with no increase in abscess and draining fistula counts. 

• PIONEER I & II results were pooled. Retreatment was evaluated for patients 
receiving ADAew in the OLE following withdrawal (placebo) or dose reduction 
(ADAeow) in Period B.

• The patients in this analysis from PIONEER I & II were intent-to-treat.
• Treatment groups are listed by treatment received in Period A/Period B/OLE.

Table 3. Patient Status, PIONEER OLE

Patient Status

ADAew/ew/ew  
N=88

ADAew/eow/ew  
N=90

ADAew/pbo/ew  
N=92

n % n % n %
Dosed 88 100 90 100 92 100
Completed study 37 42.0 44 48.9 44 47.8
Discontinued study 51 58.0 46 51.1 48 52.2

Primary reason:
AE 7 8.0 11 12.2 5 5.4
Lack of efficacy 15 17.0 10 11.1 17 18.5
Withdrew consent 15 17.0 9 10.0 16 17.4
Lost to follow up 7 8.0 11 12.2 8 8.7
Exceeded protocol specified number 
of interventions 0 0 0 0 1 1.1

Protocol deviations 1 1.1 0 0 0 0
Other 6 6.8 5 5.6 1 1.1

Abbreviations: AE=adverse event

Table 2. Baseline Patient Characteristics, PIONEER OLE
ADAew/ew/ew  

N=88
ADAew/eow/ew 

N=90
ADAew/pbo/ew 

N=92
n % n % n %

Sex Female 56 63.6 60 66.7 50 54.3

Male 32 36.4 30 33.3 42 45.7

Race White 81 92.0 70 77.8 75 81.5

Black 4 4.5 16 17.8 12 13.0

Other 3 3.4 4 4.4 5 5.4

BMI,a  
kg/m2

<25 (normal weight) 14 15.9 19 21.1 20 22.0

25 to <30 (overweight) 23 26.1 23 25.6 17 18.7

30 to <40 (obese) 40 45.5 35 38.9 42 46.2

≥40 (morbidly obese) 11 12.5 13 14.4 12 13.2

Nicotine user 52 59.1 55 61.1 48 52.2

Hurley Stage II 42 47.7 47 52.2 51 55.4

III 46 52.3 43 47.8 41 44.6

Median Range Median Range Median Range

Age, year 35.5 18-64 36.0 19-63 35.0 20-67

Lesion count AN 9.0 3-71 9.0 3-78 10.0 3-50

Draining fistulas 2.0 0-19 2.0 0-20 2.5 0-20

Abscess 1.0 0-13 2.0 0-14 1.0 0-17

Inflammatory nodules 7.0 0-69 7.0 2-76 8.0 0-38

Modified Sartorius Score 103.0 158-1093 100.0 139-433 107.0 162-397

Prior HS duration, years 10.3 1.0-40.4 8.5 1.1-32.9 8.2 1.1-43.5

Pain at worst, NRS 4.6 0-9.7 4.7 0-10.0 4.4 0-8.4

DLQI, range 0-30 16.0 2-30 14.5 1-30 14.0 0-30

hsCRP, mg/L 6.5 0.2-189.0 7.8 0.3-104.0 9.1 0.2-95.2
a. Data missing: BMI, ADAew/pbo/ew, n=1.
Abbreviations: ADA=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo; BMI, body mass index; AN=total 
abscess and inflammatory nodule count; HS=hidradenitis suppurativa; NRS=numerical rating scale; DLQI=Dermatology Life Quality Index score; 
hsCRP=high-sensitivity C-reactive protein. 

Figure 2. Patients Achieving HiSCR, n (%), by OLE Dose Groups

Abbreviations: ADA=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo.

34.1

52.3

62.5 62.5
56.8

60.2

56.8

39.8

55.6 54.4 57.8

56.7
56.7

52.2

34.1

51.1 52.2
58.7

55.4 53.3
45.7

0

20

40

60

80

100

2 12 36 60 84 108 120

P
a

tie
n

t
s
, 

%

ADA ew/ew/ew, N=88 ADA ew/eow/ew, N=90 ADA ew/pbo/ew, N=92

Week:

30 (N=88) 46 55 55 50 53 50
35 (N=88) 50 49 52 51 51 47
31 (N=91) 47 48 54 51 49 42

n=

|Period A|-------Period B-------|------------------------------------------Period C------------------------------------------|

34.1

53.5

63.2
66.7 66.7

75.0

69.6

39.8

56.2 54.1 61.6
59.0 60.0

53.7

65.9

51.6 53.5

71.6
67.7 66.1

53.8

0

20

40

60

80

100

2 12 36 60 84 108 120

P
a

tie
n

t
s
, 

%

ADA ew/ew/ew ADA ew/eow/ew ADA ew/pbo/ew

Week:

31/91 47/91 46/86 48/67 42/62 37/56 28/52
35/88 50/89 46/85 45/73 36/61 33/55 29/54
31/91 47/91 46/86 48/67 42/62 37/56 38/52

n/N=

|Period A|-------Period B-------|------------------------------------------Period C------------------------------------------|

Last Observation Carried Forward

As Observed

SAFETY
• The rate of any treatment-emergent adverse event (AE) was similar among the 

treatment groups (Figure 3). The rate of serious infections was low, and similar 
among the treatment groups.

Figure 3. Rate of Treatment-Emergent Adverse Events

Abbreviations: ADA=adalimumab; ew=every-week dosing; eow=every-other-week dosing; pbo=placebo; AE=adverse event; TB=tuberculosis;  
d/c=discontinued.

86.4

13.6 14.8

71.6

3.4

23.0

77.8

16.7
12.2

57.8

1.1 2.2

81.5

20.7

8.7

51.1

2.2 3.3

0

20

40

60

80

100

P
a

tie
n

t
s
, 

%

ADA ew/ew/ew, N=88

ADA ew/eow/ew, N=90

ADA ew/pbo/ew, N=92

Any AE Serious AE Leading to

study drug d/c

Infection Serious 
infection

TB

(active or latent)

n= 76 70 75 12 15 19 13 11 8 63 52 47 3 1 2 2 2 3

• Lymphoma was reported by one patient (ADAew/pbo/ew), non-melanoma skin 
cancer (NMSC) was reported by one patient (ADAew/pbo/ew), and malignancy 
other than lymphoma or NMSC, by 2 patients (one ADAew/eow/ew and one 
ADAew/pbo/ew).

• Serious AE infections for ADAew/ew/ew were reported by 3.4% of patients 
(cellulitis, n=1; pneumonia, n=2); for ADAew/eow/ew, 1.1% (vulval abscess, 
n=1), and for ADAew/pbo/ew, 2.2% (cellulitis, n=1; pilonidal cyst, n=1).

• There were no deaths in these 3 groups.

DISCLOSURES
AKl received honoraria as a consultant and grants as an investigator from Janssen, AbbVie, Amgen, and Novartis and has received 
fellowship funding from Janssen. MO received honoraria from AbbVie for advisory board participation and speaker services, and from 
AbbVie, Gilead Science, and Crescendo Biosciences for consultant services. Dr. Okun was an AbbVie employee during this study. GM 
received a salary as AbbVie employees, and may have also received stocks and/or stock options.
AbbVie Inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and 
writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development, review, 
and approval, and in the decision to submit this publication.
The authors would like to acknowledge Piyalal Karunaratne, former AbbVie employee, for statistical support, and Jody Bennett, 
employed by AbbVie, for medical writing support in the production of this publication.

OBJECTIVE

MATERIALS & METHODS

RESULTS

EFFICACY 
• Patients sustained response to ADAew throughout PIONEER and the OLE, 

regardless of whether they experienced dose reduction or dose withdrawal 
during Period B (week 12-36). 

• More patients who remained on ADAew throughout PIONEER and the OLE, 
achieved response as measured by HiSCR (Figure 2). 

CONCLUSIONSREFERENCES

Presented at the Fall Clinical Dermatology Conference - 36th Anniversary • Las Vega, Nevada • October 12 – 15, 2017


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