STUDY: / Authors: Asahina et al.106
Year: 2010
Study name: The Adalimumab M04-688 Study Group
Country: Japan
Quality rating: Fair
FUNDING: / Sponsored by Abbott Japan, Tokyo, Japan, and Eisai, Tokyo, Japan; Abbot Laboratories provided medical writing support.
RESEARCH OBJECTIVE: / To evaluate the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis.
DESIGN & SIZE: / Study design: Phase II/III RCT
Setting: multicenter (42 sites in Japan)
Number screened: Not Reported
Number eligible: 235 consented
Number enrolled: 169
Run-in/Wash-out period: 14 days for topical therapies and phototherapy, 28 days for systemic therapy and PUVA.
INTERVENTION:
Dose:
Duration:
Sample size: / Drug 1
Adalimumab 40mg every other week
24 weeks
38 / Drug 2
Adalimumab 40mg every other wk starting wk 2, after loading dose of 80mg at wk 0
24 weeks
43 / Drug 3
Adalimumab 80mg every other week
24 weeks
42 / Drug 4
Placebo every other week
24 weeks
46
INCLUSION CRITERIA: / ≥20 years of age, a clinical diagnosis of moderate to severe chronic plaque psoriasis, defined by a score of 12 or greater on the Psoriasis Area and Severity Index (PASI) and body surface area (BSA) involvement of 10% or greater, for at least 6 months, during which time plaque psoriasis was stable for at least the recent two months
EXCLUSION CRITERIA: / previous exposure to anti-TNF therapy, other active skin diseases or skin infections, diagnosis of systemic lupus erythematosus, scleroderma, or rheumatoid arthritis, history of central nervous system demyelinating disease, cancer, lymphoma, leukemia, tuberculosis, or lymphoproliferative disease, positive serology for anti-HIV antibody, hepatitis B surface antigen, anti-hepatitis C antibody, active infectious disease, immunosuppressive disease, or abnormal hematological, hepatic, or renal values
OTHER MEDICATIONS/ INTERVENTIONS ALLOWED: / weak or medium-potency topical corticosteroids to palms, soles, face, scalp, and groin
Authors: Asahina et al.
Year: 2010
POPULATION CHARACTERISTICS: / Adalimumab 40mg / Adalimumab 40mg
with 80mg loading dose / Adalimumab 80mg / Placebo
Mean age (years): / 47.8±12.81 / 44.2±14.32 / 43.5±12.40 / 43.9±10.75
Sex (% female): / 6 (15.8%) / 8 (18.6%) / 7 (16.7%) / 5 (10.9%)
Ethnicity: / Japanese / Japanese / Japanese / Japanese
Class naïve: / 100% / 100% / 100% / 100%
Other germane population qualities:
· Mean PASI
· Mean body surface area involvement / 25.44±8.977
43.3% / 30.24±10.946
48.3% / 28.27±11.029
46.1% / 29.10±11.767
46.7%
· Mean duration of psoriasis / 14.2 yrs ±9.29 yrs / 14.0 yrs ±7.36 yrs / 11.6 yrs ±7.45 yrs / 15.5 yrs ±8.83 yrs
· Received prior systemic therapy of nonbiologics within 6 mo prior to screening (%) / 47.4% / 41.9% / 42.9% / 37.0%
· Phototherapy received within 6 months prior to screening (%) / 18.4% / 23.3% / 16.7% / 41.3%
RESULTS: / Primary Outcome Measures:
%of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16: Drug 1: 57.9%; Drug 2: 62.8%; Drug 3: 81.0%; Placebo 4.3% (p<0.001).
Secondary Outcome Measures:
% of patients achieving PASI 50, PASI 90 and Physicians Global Assessment of “clear” or “minimal”, changes in health-related QOL were assessed by the Dermatology Life Quality Index (DLQI) and Short Form 36 (SF-36) Health Survey at week 16; PASI 50: Drug 1: 73.7%; Drug 2: 81.4%; Drug 3: 90.5%; Placebo 19.6%; PASI 90: Drug 1: 36.8%; Drug 2: 39.5%; Drug 3: 61.9%; Placebo: 0%; PGA “Clear” or “Minimal”: Drug 1: 44.7%; Drug 2: 60.5%; Drug 3: 78.6%; Placebo: 4: 8.7%; DLQI change from baseline to week 16: Drug 1: -3.9; Drug 2: -5.1; Drug 3: -6.8; Placebo:+1.0 (p<0.001 for PASI, PGA, and DLQI); SF-36change from baseline to week 16: Drug 1: 3.7 (p<0.05); Drug 2: 4.6 (p<0.01); Drug 3: 4.9 (p<0.001); Placebo: -0.4(p>0.05).
Authors: Asahina et al.
Year: 2010
METHOD OF ADVERSE EVENTS REPORTING: / Adverse events were assessed at each, every other week, visit. Laboratory evaluations and vital signs were conducted at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24.
ADVERSE EVENTS (%): / Drug 1 / Drug 2 / Drug 3 / Drug 4
Overall adverse effects reported: / 37 (97.4%) / 39 (90.7%) / 38 (90.5%) / 41 (89.1)
· Infections / 55.3% / 41.9% / 50.0% / 50.0%
· URTI
· abnormal LFT / see below / see below / see below / see below
· herpes simplex
· pneumonia
· tb / 0% / 0% / 0% / not stated: assume 0%
· ISR / 15.8% / 18.6% / 14.3% / 6.5%
· ALT / 15.8% / 16.3% / 4.8% / 6.5%
· AST / 7.9% / 9.3% / 2.4% / 4.3%
· GGT
· Hepatic event
· Hepatobiliary disorders / 13.2%
39.5%
7.9% / 2.3%
30.2%
7.0% / 2.4%
23.8%
11.9% / 0%
8.7%
0%
ATTRITION (overall):
ATTRITION (treatment specific):
Attrition overall:
Attrition due to adverse events: / Overall attrition: 22 (13.0%)
Attrition differential high: Possibly, for comparisons of Drug 1 and 3 vs Drug 2
Drug 1
4 (10.5%)
2 (5.3%) / Drug 2
8 (18.6%)
5 (11.6%) / Drug 3
4 (9.5%)
3 (7.1%) / Drug 4
6 (13.0%)
5 (10.9%)
URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosis
Evidence Table 7. Targeted Immune Modulators – Plaque PsoriasisSTUDY: / Authors: Brimhall et al.107
Year: 2008
Country:
FUNDING: / None
DESIGN: / Study design: Systematic review
Number of patients: 7,931
AIMS OF REVIEW: / To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasis
STUDIES INCLUDED IN META-ANALYSIS / ALE (three trials) n=1289
EFA (five trials) n=3130
ETA (four trials) n=2017
INF (four trials) n=1495
TIME PERIOD COVERED: / MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. were searched from inception to June 2005; an updating search was conducted in July 2006 to capture reports from the interim period
CHARACTERISTICS OF INCLUDED STUDIES: / Randomized, controlled, double-blind, monotherapy trials
CHARACTERISTICS OF INCLUDED POPULATIONS: / Patients with psoriasis
Authors: Brimhall et al.
Year: 2008
CHARACTERISTICS OF INTERVENTIONS: / ALE vs. placebo
EFA vs. placebo
ETA vs. placebo
INF vs. placebo
MAIN RESULTS: / NNT (95% CI) / PASI 50 / PASI 75 / PASI 90
ALE / 4(3.07–4.48) / 8 (5.05–12.20) / N/A
EFA / 3(3.26–4.48) / 4(3.36–5.24) / N/A
ETA / N/A / 3(2.07–2.49) / 5(4.29–5.88)
INF / N/A / 2(1.24–1.38) / 2(1.67–2.31)
ADVERSE EVENTS: / NNH (95%CI)
ALE / 15(7.63–142.86)
EFA / 9(7.30–13.88)
ETA / 46(–48–14)
INF / 9(5.99–19.61)
COMPREHENSIVE LITERATURE SEARCH STRATEGY: / Yes
STANDARD METHOD OF APPRAISAL OF STUDIES: / Yes
QUALITY RATING: / Fair
Evidence Table 7. Targeted Immune Modulators – Plaque Psoriasis
STUDY: / Authors: Gordon et al.108and Shikiar et al.109
Year: 2006
Country: US and Canada
FUNDING: / Abbott Labs
RESEARCH OBJECTIVE: / Efficacy and safety of ADA in patients with moderate to severe plaque psoriasis. After 12 week all patients were switched to active arms.
DESIGN: / Study design: RCT
Setting: Multicenter
Sample size: 147
INTERVENTION:
Dose:
Duration:
Sample size: / Placebo
N/A
12 weeks
52 / ADA EOW
80 mg at week 0 and 40 mg EOW
12 weeks
45 / ADA Weekly
80 mg at week 0 and 40 mg weekly
12 weeks
50
INCLUSION CRITERIA: / Men and women age 18 years and older with plaque psoriasis of at least 1-year duration and involving 5% or more of their body surface area.
EXCLUSION CRITERIA: / History of neurologic symptoms suggestive of central nervous system demyelinating disease, or with a history of cancer or lymphoproliferative disease (other than successfully treated non-melanoma skin cancer or localized carcinoma in situ of the cervix)
OTHER MEDICATIONS/ INTERVENTIONS ALLOWED: / Low to mid dose topical corticosteroids
Authors: Gordon et al. and Shikiar et al.
Year: 2006
POPULATION CHARACTERISTICS:
Mean age (years):
Sex (% female):
Ethnicity (% Caucasian):
Other germane population qualities:
· Mean PASI
· Mean body surface area involvement
· Mean duration of psoriasis -yrs
· Received prior systemic therapy (%) / Groups similar at baseline:
Placebo
43
35
92
16.0
28
19
NR / ADA EOW
46
29
89
16.7
29
21
NR / ADA Weekly
44
34
90
14.5
25
18
NR
OUTCOME ASSESSMENT: / Primary Outcome Measures: PASI 75% and DLQI at 12 weeks
Secondary Outcome Measures: PASI 75 at 24 weeks and PGA, SF-36 Health Survey, and Euro QoL-5D (EQ-5D)
Timing of assessments: weeks 0, 1, 2, and 4, and then every 4 or 8 weeks thereafter.
RESULTS: / Health Outcome Measures:
· PASI 75% at 12 weeks Placebo 4% ADA EOW 53% ADA WK 80%
· PASI 100% at 12 weeks Placebo 0% ADA EOW 11% ADA WK 26%
· DLQI change at 12 weeks Placebo 1.3% (3.3, 0.7) ADA EOW 10.8 (13.1, 8.5) ADA WK 11.5 (13.6, 9.4) ADA(both) vs. placebo P < 0.001
· EQ-5D Index score change at 12 weeks Placebo 0.01 (0.07, 0.1) ADA EOW 0.21 (0.11, 0.31) ADA WK 0.19 (0.09, 0.28) ADA(both) vs. placebo P < 0.001
· EQ-5D VAS change at 12 weeks Placebo 0.5 (5.7, 6.8) ADA EOW 17.9 (10.5, 25.2) ADA WK 10.7 (4.1, 17.4) ADA EOW vs. placebo P < 0.001 and ADA WK vs. placebo P = 0.013
· SF-36 PCS change at 12 weeks Placebo 0.5 (2.4, 3.5) ADA EOW 3.6 (0.2, 7.0) ADA WK 5.5 (2.4, 8.6) ADA EOW vs. placebo P = 0.118 and ADA WK vs. placebo P = 0.010
· SF-36 MCS change at 12 weeks Placebo 0.1 (3.5, 3.3) ADA EOW 7.8 (3.9, 11.8) ADA WK 5.2 (1.6, 8.9) ADA EOW vs. placebo P < 0.001 and ADA WK vs. placebo P = 0.017
Authors: Gordon et al. and Shikiar et al.
Year: 2006
ADVERSE EVENTS:
Overall adverse effects reported:
· infections
· Dyspepsia
· Nausea
· Injection site pain / Placebo
67.3%
0
0
5.8%
5.8% / ADA EOW
62.2%
0
0
6.7%
6.7% / ADA Weekly
78.0%
2.0%
8.0%
2.0%
12.0%
Significant differences in adverse events: / None reported
ANALYSIS: / ITT: Yes
Post randomization exclusions: 1
ADEQUATE RANDOMIZATION: / NR
ADEQUATE ALLOCATION CONCEALMENT: / NR
BLINDING OF OUTCOME ASSESSORS: / NR
ATTRITION (overall):
ATTRITION (treatment specific):
Attrition overall:
Attrition due to adverse events: / Overall attrition: 7 (5%)
Attrition differential high: No
Placebo
3.8%
1.9% / ADA EOW
4.4%
4.4% / ADA Weekly
6.0%
6.0%
QUALITY RATING: / Fair
Evidence Table 7. Targeted Immune Modulators – Plaque Psoriasis
STUDY: / Authors: Griffiths et al.110
Year: 2010
Study name: -
Country: Worldwide
Quality rating: FAIR
FUNDING: / Centocor Research and Development (pharmaceutical industry)
RESEARCH OBJECTIVE: / To compare two biologic agents, ustekinumab and etanercept, for the treatment of psoriasis
DESIGN & SIZE: / Study design: head-to-head RCT
Setting: multi-center
Number screened: 1,175
Number eligible: not reported
Number enrolled: 903
Run-in/Wash-out period: no
INTERVENTION:
Dose:
Duration:
Sample size: / ETA
50 mg twice weekly
12 weeks
347 / UST
45 mg at weeks 0 and 4
12 weeks
209 / UST
90 mg at weeks 0 and 4
12 weeks
347
INCLUSION CRITERIA: / ≥18 years of age, diagnosis of plaque psoriasis at least 6 months earlier, candidates for phototherapy or systemic treatment, score ≥12 on PASI, score ≥3 on physician’s global assessment; involvement of ≥10% of body-surface area; inadequate response, intolerance or contraindication to ≥1 conventional systemic agent (i.e., methotrexate, cyclosporine, or psoralen plus UVA), and no previous treatment with UST or ETA.
EXCLUSION CRITERIA: / Nonplaque or drug-induced forms of psoriasis, recent serious infection, history of chronic or recurrent infectious disease, known malignant condition (other than treated basal- or squamous-cell skin cancer or cervical cancer in situ with no evidence of recurrence for ≥5 years), receipt of conventional systemic therapy or phototherapy within 4 weeks before enrollment, topical psoriasis agents within 2 weeks, investigational drugs within 4 weeks or 5 half-lives, biologic agents within 3 months or 5 half-lives.
OTHER MEDICATIONS/ INTERVENTIONS ALLOWED: / None reported
Authors: Griffiths et al.
Year: 2010
POPULATION CHARACTERISTICS: / ETA / UST 45 mg / UST 90 mg
Mean age (years): / 45.7 / 45.1 / 44.8
Sex (% female): / 29.1% / 36.4% / 32.6%
Ethnicity: / 91.1% white / 92.3% white / 89.0% white
Class naïve: / 88.2% / 87.6% / 89.6%
Other germane population qualities:
· Mean PASI / 18.6 / 20.5 / 19.9
· Mean body surface area involvement / 23.8% / 26.7% / 26.1%
· Mean duration of psoriasis / 18.8 years / 18.9 years / 18.7 years
· Received prior systemic therapy (%) / 57.3% / 61.7% / 52.4%
RESULTS: / Primary Outcome Measures:
56.8% of ETA group had ≥75% improvement in PASI score compared with 67.5% of UST 45 mg group (P=0.01 vs. ETA)and 73.8% of UST 90 mg group (P<0.001 vs. ETA).
Secondary Outcome Measures:
23.1% of ETA group had ≥90% improvement in PASI score compared with 36.4% of UST 45 mg group (P<0.001 vs. ETA) and 44.7% of UST 90 mg group (P<0.001 vs. ETA).
49.0% of ETA group had cleared or minimal disease (physician’s global assessment score=0 or 1) compared with 65.1% of UST 45 mg group (P<0.001 vs. ETA) and 70.6% of UST 90 mg group (P<0.001 vs. ETA).
8.6% of ETA group had cleared disease (physician’s global assessment score=0) compared with 16.3% of UST 45 mg group (P=0.006 vs. ETA) and 26.2% of UST 90 mg group (P<0.001 vs. ETA).
Authors: Griffiths et al.
Year: 2010
METHOD OF ADVERSE EVENTS REPORTING: / Safety was evaluated by assessing adverse events and routine hematologic and laboratory values. Possible major cardiovascular events were adjudicated by an independent panel of academic cardiologists. Serum samples were evaluated for antibodies to UST.
ADVERSE EVENTS (%): / ETA / UST 45 mg / UST 90 mg
Overall adverse effects reported: / 70.0% / 66.0% / 69.2%
· Infections / 29.1% / 30.6% / 29.7%
· URTI / 5.8% / 6.2% / 6.3%
· abnormal LFT / NR / NR / NR
· herpes simplex / NR / NR / NR
· pneumonia / NR / NR / NR
· tb / NR / NR / NR
· ISR / 24.8% / 4.3% / 3.7%
· nonmelanoma skin cancer / 0.0% / 1.0% / 0.3%
· back pain / 2.0% / 6.7% / 4.3%
· ≥ serious adverse event / 1.2% / 1.9% / 1.2%
ATTRITION (overall):
ATTRITION (treatment specific):
Attrition overall:
Attrition due to adverse events: / Overall attrition: 2.7%
Attrition differential high: No
ETA
3.2%
2.3% / UST 45 mg
3.8%
1.9% / UST 90 mg
1.4%
1.2%
URTI: upper respiratory tract infection; LFT: liver function test; ISR: injection site reaction; tb: tuberculosis