| Study characteristics |
| Methods |
RCT, placebo‐controlled, double‐blind trial, phase 2
Date of study: February 2014 ‐ July 2015
Location: world‐wide |
| Participants |
Randomised: 166 participants
Inclusion criteria
BMI ≥ 18.5 and < 40 kg/m2 Stable moderate‐severe chronic plaque‐type psoriasis with or without psoriatic arthritis involving ≥ 10% body surface area, with disease severity PASI ≥ 12 and sPGA score of moderate and above (score of ≥ 3) at screening visit and visit 2 (randomisation), as assessed by the investigator Psoriasis disease duration of ≥ 6 months prior to screening, as assessed by the investigator Patients must be candidates for systemic psoriasis treatment or phototherapy, as assessed by the investigator Patients must be suitable candidates for ustekinumab (Stelara®) therapy as given in the local labelling Patient must give informed consent and sign an approved consent form prior to any study procedures in accordance with GCP and local legislation
Exclusion criteria
Patients with guttate, erythrodermic, or pustular psoriasis and patients with drug‐induced psoriasis, as diagnosed by the investigator Evidence of current or previous clinically‐significant disease, medical condition other than psoriasis, or finding of the medical examination (including vital signs and ECG), that in the opinion of the investigator, would compromise the safety of the patient or the quality of the data. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgement, even if other eligibility criteria are satisfied. (Psoriatic arthritis is not considered an exclusion criterion) Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders, or history of orthostatic hypotension, fainting spells or blackouts, that in the investigator's judgement, could jeopardise the safe conduct of the study Clinically important acute or chronic infections including hepatitis and HIV
With regards to TB the following applies:
Have signs or symptoms suggestive of current active or latent TB upon medical history, physical examination and/or a chest radiograph (both posterior‐anterior and lateral views, taken within 3 months prior to the first administration of study drug and read by a qualified radiologist) Have history of latent or active TB prior to screening, except for patients who have documentation of having completed an adequate treatment regimen ≥ 6 months prior to the first administration of study agent Have positive IGRA testing (QuantiFERON‐TB Gold) within 2 months prior to or during screening, in which active TB has not been ruled out, except for patients with history of latent TB and documentation of having completed an adequate treatment regimen ≥ 6 months prior to the first administration of study agent Have had a live vaccination ≤ 12 weeks prior to randomisation (visit 2). Patients must agree not to receive a live vaccination during the study. No BCG vaccines should be given for 1 year prior to randomisation (visit 2), during the study and for one year after last administration of study drug (according to the Stelara® SPC). History of clinically‐significant hypersensitivity to a systemically administered biologic agent or its excipient History of malignancy in the past 5 years or suspicion of active malignant disease except treated cutaneous squamous cell or basal cell carcinoma Has received any therapeutic agent directly targeted to IL‐12, IL‐23 (including ustekinumab (Stelara®)) Use of biologic agents within 12 weeks (infliximab, etanercept, adalimumab, other biologics) prior to treatment, systemic anti‐psoriatic medications or phototherapy within 4 weeks prior to treatment, or topical anti‐psoriasis medications within 2 weeks prior to treatment
Dropouts and withdrawals
Risan 18 (4), Risan 90 (2), Risan 180 (2), USK (1)
Lost to follow‐up: Risan 18 (1), Risan 90 (0), Risan 180 (0), USK (0) AEs: Risan 18 (1), Risan 90 (1), Risan 180 (0), USK (1) Others: Risan 18 (2), Risan 90 (1), Risan 180 (2), USK (0)
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| Interventions |
Intervention
A. Drug: Risankizumab (low dose) (18 mg BI 655066 administered by SC injection plus 2 placebo‐matching BI 655066 injections at week 0, followed by 2 placebo‐matching BI 655066 injections each at weeks 4 and 16), n = 43
Control intervention
B. Drug: BI 655066 (median dose) (90 mg BI 655066 administered by SC injection plus 2 placebo‐matching BI 655066 injections at week 0, followed 90 mg BI 655066 plus 1 placebo‐matching BI 655066 injection at weeks 4 and 16), n = 41
C. Drug: BI 655066 (high dose) (180 mg BI 655066 administered by SC injection as 2 injections plus a placebo‐matching BI 655066 injection at week 0, followed 180 mg BI 655066 administered as 2 injections at 2eeks 4 and 16), n = 42
D. Drug: ustekinumab (Stelara administered by SC injection plus 2 saline injections at week 0, Stelara injection plus 1 saline injection at weeks 4 and 16. Stelara dose was 45 mg for participants with body weight ≤ 100 kg at randomisation or 90 mg for participants with body weight > 100 kg at randomisation), n = 40 |
| Outcomes |
At week 12
Primary outcome
Secondary outcomes
|
| Notes |
Funding
Quote (p 1553): "The trial was funded by Boehringer Ingelheim"
Conflicts of interest
Quote (p 1560): "Disclosure forms provided by the authors are available with the full text of this article at NEJM.org." |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Quote (p 1552): "This 48‐week, multicenter, randomized, dose‐ranging, phase 2 trial."
Comment: no description of the method used to guarantee random sequence generation |
| Allocation concealment (selection bias) |
Unclear risk |
Comment: no description of the method used to guarantee allocation concealment |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
Quote (p 1552): "The trial was double blind within the risankizumab dose groups and single blind (to patients) with regard to drug (ustekinumab or risankizumab). All efficacy assessments were conducted by an assessor who was unaware of the treatment assignments."
Comment: No blinding |
| Blinding of outcome assessment (detection bias)
All outcomes |
Low risk |
Quote (p 1552): "The trial was double blind within the risankizumab dose groups and single blind (to patients) with regard to drug (ustekinumab or risankizumab). All efficacy assessments were conducted by an assessor who was unaware of the treatment assignments."
Comment: probably done |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Dealing with missing data
Quote (p 1553): "Primary and other end points were analyzed on an intention‐to‐treat basis...
In the primary analyses, last observation carried forward was prespecified in the trial protocol as the method of handling missing data; a sensitivity analysis with nonresponse imputation was also performed"
166 randomised, 166 analysed
Comment: Done |
| Selective reporting (reporting bias) |
Low risk |
Comment: the protocol for the study was available on ClinicalTrials.gov (NCT02054481)
The prespecified outcomes and those mentioned in the Methods section appeared to have been reported
Results posted on ClinicalTrials.gov |
