Download Effectiveness of adalimumab in treating patients with active psoriatic

Supplementary material for publication online only:
Effectiveness of adalimumab in treating patients with active psoriatic
arthritis (PsA) and predictors of good clinical responses for arthritis,
skin, and nail lesions
METHODS
Inclusion/exclusion criteria
Main inclusion criteria were: age ≥18 years, PsA diagnosed by a rheumatologist; ≥3
tender and ≥3 swollen joints, previous treatment with ≥1 disease-modifying
antirheumatic drugs (DMARDs); and enrollment in accordance with each participating
country’s current guidelines for anti-TNF treatment of PsA. Allowed current
antirheumatic medications: DMARDs, nonsteroidal anti-inflammatory drugs, and oral
glucocorticoids (≤10 mg prednisolone equivalent/d), as well as topical psoriasis therapy,
if the dosage was stable.
Exclusion criteria were: medication prior to enrollment as follows: etanercept within ≤3
weeks, infliximab within ≤2 months, combination of methotrexate (MTX) and
leflunomide (LEF) within ≤4 weeks, any combination of cyclosporine and another
DMARD within ≤4 weeks, and ultraviolet A (UVA) phototherapy, including psoralen
(PUVA) within ≤2 weeks. Further exclusion criteria encompassed a history of rheumatic
disorders other than PsA; any uncontrolled medical condition that would put the patient
at risk (eg, diabetes mellitus, ischemic heart disease); history or signs of demyelinating
disease; active tuberculosis (TB) or histoplasmosis; malignancy (except for treated
squamous or basal cell carcinoma); positive serology for hepatitis B, hepatitis C, or
human immunodeficiency virus; and infections requiring hospitalisation or intravenous
antibiotics within 30 days or oral antibiotics within 14 days of enrolment. Patients
diagnosed with latent TB by the Mantoux tuberculin skin test, T-SPOT.®TB test, or chest
radiograph or with medical history suggesting risk factors for TB were excluded unless
prophylactic therapy for latent TB was initiated before the first adalimumab injection.
Study design
STEREO (The SafeTy and Efficacy of Adalimumab in Patients With Active Psoriatic
Arthritis — An Open-Label, Multinational Study to Evaluate the Response to EveryOther Week Adalimumab When Added to Insufficient Standard Therapy Including
Patients Who Failed Prior Treatment With Other TNF Inhibitors) was a prospective,
open-label, uncontrolled study conducted in nine European countries. Patients selfadministered adalimumab (Abbott Laboratories, Abbott Park, IL) 40 mg subcutaneously
every other week in addition to their pre-existing antirheumatic treatments for 12 weeks.
Subsequently, patients who benefited from adalimumab therapy could continue up to
Week 20 if adalimumab was not commercially available. Evaluations for effectiveness
and safety were conducted at Weeks 2, 6, 12, and 20, as applicable. Observed data at
Week 12 were used for all effectiveness analyses, and safety data were analysed based on
the complete treatment period of each patient. Data were analysed using SAS version 8.2
(SAS Inc., Cary, NC).
Adverse events (AEs) were captured from the time of first adalimumab injection until 70
days (5 serum half-lives) following the last adalimumab injection. AEs were coded using
the Medical Dictionary for Regulatory Affairs (MedDRA version 9.1).
RESULTS
Effectiveness
Supplementary Table 1
Observed improvement in PsA signs and symptoms from baseline to Week 12
Baseline
Effectiveness
measure
Tender joint count
(0–78)
Swollen joint count
(0–76)
DAS28
CRP (mg/dL)
Erythrocyte
sedimentation rate
(mm/first hr)
PaGA of disease
activity (0–100 mm
VAS)
PhGA of disease
activity (0–100 mm
VAS)
Week 12
Mean
n Mean±SD change±SD
414 8.1±12.1 –11.7±11.8
Mean %
change from
baseline
–61
n
442
Mean±SD
20.1±14.4
442
10.3±7.7
414
2.5±3.9
–7.6±6.9
–73
416
441
419
4.9±1.2
1.7±1.9
23±20
406
405
408
2.7±1.4
0.6±1.0
11±13
–2.3±1.4
–1.1±1.8
–12±17
–45
–26
–36
439
61±20
412
28±25
–32±29
–49
442
50±19
411
17±16
–33±21
–59
Patient’s assessment
439
64±21
412
28±25
–35±29
–51
of pain (0–100 mm
VAS)
HAQ DI (0–3)
439 1.24±0.62 412 0.71±0.66 –0.52±0.52
–47
DLQI (0–30)*
310
7.9±6.9
263 3.0±4.0
–4.6±5.8
–41
*Only patients with DLQI >0 at baseline.
CRP, C-reactive protein (reference value, 0.4 mg/dL); DAS28, Disease Activity Score
based on 28-joint count, erythrocyte sedimentation rate, and patient’s general health;
DLQI, Dermatology Life Quality Index; HAQ DI, Health Assessment Questionnaire
Disability Index; PaGA, Patient’s Global Assessment of disease activity; PhGA,
Physician’s Global Assessment of disease activity; VAS, visual analogue scale.
Predictors of good clinical response at Week 12
Supplementary Table 2
Crude odds ratios for good clinical responses to adalimumab at Week 12, as
defined by ACR50 or good EULAR response
ACR50
Good EULAR
Predictors
OR
95% CI
P-Value OR
95% CI
P-Value
Sex (male vs. female)
2.40
1.61–3.57
<0.001 2.42 1.59–3.69 <0.001
HAQ-DI (per unit)
0.52
0.37–0.72
<0.001 0.53 0.37–0.76 <0.001
Treatment with SSZ*
1.86
1.01–3.43
0.050
2.89 1.35–6.17
0.006
Systemic
glucocorticoids (≤10
0.64
0.42–0.98
0.050
0.49 0.31–0.77
0.002
mg/day)*
Dactylitis*
1.22 0.78–1.93
0.421
1.76
1.14–2.72
0.012
CRP (per mg/dL)
1.01 0.91–1.13
0.821
1.14
1.02–1.27
0.017
SJC [0–76] (≥5 vs.<5)
1.12 0.64–1.96
0.670
2.37
1.38–4.09
0.002
≥1 inflamed big joint*
0.98
0.66–1.44
0.921
0.59 0.39–0.89
0.015
Prior anti-TNF
0.65
0.37–1.13
0.162
0.45 0.25–0.80
0.007
therapy*
Prior DMARD use (≥2
1.04
0.68–1.60
0.913
2.03 1.29–3.19
0.002
vs. <2)
Age (per year)
0.99
0.97–1.00
0.136
0.97 0.96–0.99
0.005
Treatment with
1.02
0.67–1.56
1.000
1.36 0.87–2.11
0.176
DMARDs*
PsA duration (per year)
1.00
0.98–1.03
0.826
1.01 0.98–1.03
0.704
Arthritis duration (per
1.01
0.98–1.03
0.593
1.00 0.98–1.03
0.805
year)
Tobacco use ever vs.
0.81
0.55–1.20
0.320
1.04 0.69–1.57
0.916
never
Enthesitis*
1.28
0.85–1.92
0.253
0.97 0.63–1.50
0.912
DAS28
1.10
0.92–1.32
0.316
0.90 0.75–1.09
0.277
PaGA of disease
1.00
0.99–1.01
0.363
1.00 0.99–1.01
0.480
activity (per mm)
PhGA of disease
1.01
1.00–1.02
0.238
1.00 0.99–1.01
0.742
activity (per mm)
Pain (per mm)
1.01
1.00–1.01
0.268
1.00 0.99–1.01
0.724
PGA >moderate vs.
1.23
0.70–2.15
0.482
0.94 0.51–1.72
0.877
≤moderate
Bold figures=statistically relevant. *Yes vs. no.
PsA, psoriatic arthritis; ACR50, American College of Rheumatology response criteria
50% improvement; Good EULAR, European league against rheumatism Good
Response criteria; DMARDs, disease modifying anti-rheumatic drugs; OR, odds ratio;
CI, confidence interval; CRP, C-reactive protein (reference value, 0.4 mg/dL); OR,
odds ratio; SSZ, sulfasalazine; VAS, visual analogue scale; HAQ-DI, health assessment
questionnaire disability index; large joints, swollen shoulder, elbow, or knee or tender
hip; DAS28, Disease Activity Score based on 28-joint count; PaGA, Patient’s Global
Assessment; PhGA, Physician’s Global Assessment; PGA, Physician’s Global
Assessment of psoriasis.
Safety
At least one AE was reported for 310 (70.1%) patients during adalimumab treatment and
the 70-day follow-up. Twenty-one serious AEs were documented in 18 (4.1%) patients.
Three (0.7%) patients experienced four serious infections: one 65-year-old female
experienced TB laryngitis 13 weeks and urosepsis 24 weeks after the first adalimumab
injection. The two other serious infections were primary atypical pneumonia and tooth
abscess. One patient had a serious toxic hepatitis. No malignancies, lupus-like reactions,
congestive heart failures, or demyelinating diseases were reported in this study.