Systemic pharmacological treatments for chronic plaque psoriasis A Systematic Review and an Individual-Patient Data Network Meta-Analysis of Randomized Controlled Trials

Lead Investigator: Emilie Sbidian, University Paris Est Creteil (UPEC)
Title of Proposal Research: Systemic pharmacological treatments for chronic plaque psoriasis A Systematic Review and an Individual-Patient Data Network Meta-Analysis of Randomized Controlled Trials
Vivli Data Request: 7620
Funding Source: We applied for french ‘government agencies’ grants
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Psoriasis is a frequent immune-mediated disease with either skin or joint manifestations, or both, which has a major impact on quality of life. This is a frequent disease with a prevalence ranging from 2.2% (USA) to 8.5% (Norway). Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Systemic treatments, including biologics are proposed to moderate to severe psoriasis patients, closed to 15% of the total psoriasis population. Biologics are substances that are made from a living organism or its products and is used in the prevention, diagnosis, or treatment of cancer and immune-mediated diseases. Biological drugs include antibodies, interleukins (IL), and vaccines.

In that context, we performed a living Cochrane systematic review and network meta-analysis (NMA) (PMID: 33871055) to compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis (a total of 20 interventions), and to provide a ranking of these treatments according to their efficacy and safety. Our review showed that compared to placebo, some biologics such as infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving clearance or almost clearance of the psoriasis in people with moderate-to-severe disease based on high-certainty evidence. However, as this NMA used aggregated data, subgroups analyses were not possible.

In daily practice, choosing the best intervention option for a given patient is a challenging question and depends on the presence or not of a psoriatic arthritis, on patient’s co-morbidities or patient’s previous systemic treatment lines. Some of these characteristics were identified as prognostic factors of drug persistence rate (sex, weight, co-morbidities, previous treatment lines).

An alternative approach of NMA is an NMA of individual participant data (NMA-IPD), in which the participant-level data are obtained from trials then checked, harmonised and synthesized. Indeed, a NMA-IPD is required to compare the efficacy and the safety of systemic interventions for psoriasis, according to patients’ baseline characteristics, prognostic factors, treatments received, outcomes and follow-up details.

The objective is to conduct an NMA-IPD to provide a valid comparison between drugs and to help clinicians to choose the better drug for a given patient.

Requested Studies:

A Phase II/III, Randomized, Double-blind Study to Evaluate Efficacy and Safety of Two Different Dose Regimens of BI 655066 (Risankizumab) and Placebo and Maintenance of Response of BI 655066 (Risankizumab) Administered Subcutaneously in Japanese Patients With Moderate to Severe Chronic Plaque Type Psoriasis
Data Contributor: AbbVie
Study ID: NCT03000075
Sponsor ID: M16-004

A Randomized, Controlled, Multicenter, Open Label Study With Blinded Assessment of the Efficacy of the Humanized Anti-IL-23p19 Risankizumab Compared to FUMADERM® in Subjects With Moderate to Severe Plaque Psoriasis Who Are Naïve to and Candidates for Systemic Therapy
Data Contributor: AbbVie
Study ID: NCT03255382
Sponsor ID: M16-178

BI 655066/ABBV-066 (Risankizumab) Versus Adalimumab in a Randomized, Double Blind, Parallel Group Trial in Moderate to Severe Plaque Psoriasis to Assess Safety and Efficacy After 16 Weeks of Treatment and After Inadequate Adalimumab Treatment Response (IMMvent)
Data Contributor: AbbVie
Study ID: NCT02694523
Sponsor ID: M16-010

BI 655066/ABBV-066 (Risankizumab) Versus Ustekinumab and Placebo Comparators in a Randomized Double Blind trIal for Maintenance Use in Moderate to Severe Plaque Type Psoriasis (UltIMMa-1)
Data Contributor: AbbVie
Study ID: NCT02684370
Sponsor ID: M16-008

BI 655066 Versus Ustekinumab and Placebo Comparators in a Randomized Double Blind trIal for Maintenance Use in Moderate to Severe Plaque Type Psoriasis-2 (UltIMMa-2)
Data Contributor: AbbVie
Study ID: NCT02684357
Sponsor ID: M15-995

BI 655066 / ABBV-066 (Risankizumab) Versus Placebo In a Multicenter Randomized Double-blind Study in Patients With Moderate to Severe Chronic Plaque Psoriasis Evaluating the Efficacy and Safety With Randomized Withdrawal and Re-treatment (IMMhance)
Data Contributor: AbbVie
Study ID: NCT02672852
Sponsor ID: M15-992

A 24-Week Multicenter, Randomized, Open-Label, Parallel-Group Study Comparing the Efficacy and Safety of Ixekizumab to Fumaric Acid Esters and Methotrexate in Patients With Moderate-to-Severe Plaque Psoriasis Who Are Naive to Systemic Treatment With an Extension Period
Data Contributor: Lilly
Study ID: NCT02634801
Sponsor ID: 16190

A 52-Week Multicenter, Randomized, Blinded, Parallel-Group Study Comparing the Efficacy and Safety of Ixekizumab to Ustekinumab in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT02561806
Sponsor ID: 16012

A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Dosing Regimens in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT02513550
Sponsor ID: 15988

A 48 Weeks Study of Three Different Dose Regimens of BI 655066 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque Psoriasis (Randomised, Dose-ranging, Active-comparator-controlled (Ustekinumab), Double-blind Within Dose Groups of BI 655066)
Data Contributor: AbbVie
Study ID: NCT02054481
Sponsor ID: 1311.2

A Phase 3, Multicenter, Double-Blind, Randomized, Parallel-Arm, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Adalimumab for Treatment of Nail Psoriasis in Patients With Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT02016482
Sponsor ID: M13-674

A 12-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate to Severe Plaque Psoriasis With a Long-Term Extension Period
Data Contributor: Lilly
Study ID: NCT01646177
Sponsor ID: 13685

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Adalimumab (Humira®) in Chinese Subjects With Moderate to Severe Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT01646073
Sponsor ID: M13-606

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT01597245
Sponsor ID: 12973

A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Maintenance Dosing Period and a Long- Term Extension Period to Evaluate the Efficacy and Safety of LY2439821 in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT01474512
Sponsor ID: 12972

A Dose-Ranging And Efficacy Study of LY2439821 (An Anti-IL-17 Antibody) In Patients With Moderate-To-Severe Psoriasis
Data Contributor: Lilly
Study ID: NCT01107457
Sponsor ID: 12060

A Phase III, Multicenter Study of the Efficacy and Safety of Adalimumab Treatment in Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT00237887
Sponsor ID: M03-656

A Phase 3, Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study Comparing the Safety and Efficacy of Adalimumab to Methotrexate in Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT00235820
Sponsor ID: M04-716

A MULTICENTER, RANDOMIZED, OPEN PILOT TRIAL ASSESSING THE EFFICACY AND SAFETY OF ETANERCEPT 50 MG TWICE WEEKLY FOLLOWED ETANERCEPT 25MG TWICE WEEKLY, THE COMBINATION OF ETANERCEPT 25 MG TWICE WEEKLY AND ACITRETIN AND ACITRETIN ALONE IN PATIENTS WITH MODERATE TO SEVERE PSORIASIS.
Data Contributor: Pfizer, Inc.
Study ID: NCT00936065

A RANDOMIZED, OPEN-LABEL, TWO-PERIOD STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ETANERCEPT ON SKIN AND JOINT DISEASE IN PSORIASIS SUBJECTS WITH PSORIATIC ARTHRITIS
Data Contributor: Pfizer, Inc.
Study ID: NCT00245960

Study Comparing the Efficacy and Safety of ABT-874 to Etanercept and Placebo in Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT00691964

Study Comparing the Efficacy and Safety of ABT-874 to Etanercept and Placebo in Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT00710580

Risankizumab Versus Secukinumab for Participants With Moderate to Severe Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT03478787

A Study to Assess Safety and Efficacy of Risankizumab Using a New Formulation in Participants With Moderate to Severe Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT03875482

A 24-Week Multicenter, Randomized, Blinded, Parallel-Group Study Comparing the Efficacy and Safety of Ixekizumab to Guselkumab in Patients With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Lilly
Study ID: NCT03573323
Sponsor ID: 17119

A Phase 2/3, Randomized, Double-Blind, Placebo Controlled, Multicenter Study of Efficacy and Safety of Adalimumab in Japanese Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: AbbVie
Study ID: NCT00338754
Sponsor ID: M04-688

A Multicenter, Parallel, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Etanercept 50 mg Once Weekly in Subjects With Moderate to Severe Plaque Psoriasis
Data Contributor: Pfizer, Inc.
Study ID: NCT00333034

A Phase 2 Multicenter, Randomized, Placebo- and Active-Comparator-Controlled, Dose-Ranging Trial to Evaluate CNTO 1959 for the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis (X-PLORE)
Data Contributor: Johnson & Johnson
Study ID: NCT01483599
Sponsor ID: CR100673

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Chinese Subjects With Moderate to Severe Plaque-type Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT01008995
Sponsor ID: CR016318

A Phase 3, Multicenter, Randomized Study Comparing CNTO 1275 and Etanercept for the Treatment of Moderate to Severe Plaque Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00454584
Sponsor ID: CR013015

A Phase II, Randomized, Double-blind, Placebo-controlled, Parallel Study of Single and Multiple Dose Regimens With Subcutaneous CNTO 1275 (Human Monoclonal Antibody to IL-12) in Subjects With Moderate to Severe Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00320216
Sponsor ID: CR005416

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00307437
Sponsor ID: CR006325

A Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Trial Evaluating the Efficacy and Safety of Ustekinumab (CNTO 1275) in the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00267969
Sponsor ID: CR006328

A Placebo-Controlled Double-Blind Comparative Study of CNTO1275 in Patients With Plaque Type Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00723528
Sponsor ID: CR015166

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Korean and Taiwanese Subjects With Moderate to Severe Plaque-type Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT00747344
Sponsor ID: CR015313

A Phase 3b, Randomized, Double-blind, Active-controlled, Multicenter Study to Evaluate a “Subject-tailored” Maintenance Dosing Approach in Subjects With Moderate-to-Severe Plaque Psoriasis
Data Contributor: Johnson & Johnson
Study ID: NCT01550744
Sponsor ID: CR100708

A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Guselkumab for the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis and an Inadequate Response to Ustekinumab
Data Contributor: Johnson & Johnson
Study ID: NCT02203032
Sponsor ID: CR104918

An Exploratory Trial to Assess Naturalistic Safety and Efficacy Outcomes in Patients With Moderate to Severe Plaque Psoriasis Transitiioned to Ustekinumab From Previous Methotrexate Therapy (TRANSIT)
Data Contributor: Johnson & Johnson
Study ID: NCT01059773
Sponsor ID: CR016639

A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Study Followed by a Dose-Blind Period and Open-Label Follow-Up to Evaluate the Efficacy and Safety of Certolizumab Pegol in Subjects With Moderate to Severe Chronic Plaque Psoriasis
Data Contributor: UCB
Study ID: NCT02326298
Sponsor ID: PS0005