| Study characteristics |
| Methods |
RCT, active‐controlled, double‐blind trial (SIGNATURE)
Date of study: October 2013‐July 2016
Location: UK‐Ireland |
| Participants |
Randomised: 235 participants
Inclusion criteria
Chronic plaque‐type psoriasis diagnosed for ≥ 6 months prior to screening, aged ≥ 18 years at screening Moderate‐severe disease severity: PASI ≥ 10 and DLQI > 10 Failed to respond to systemic therapies including ciclosporin and/or methotrexate and/or PUVA (or is intolerant and/or has a contraindication to these) Previously treated with ≥ 1 anti‐TNFα for moderate or severe psoriasis but failed to respond to this (these) drug(s)
Exclusion criteria
Forms of psoriasis other than chronic plaque‐type (e.g. pustular, erythrodermic and guttate psoriasis) Drug‐induced psoriasis (i.e. new onset or current exacerbation from beta‐blockers, calcium channel inhibitors or lithium) Ongoing use of prohibited psoriasis treatments (e.g. topical or systemic corticosteroids (CS), UV therapy). Washout periods detailed in the protocol must be adhered to. Ongoing use of other non‐psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to. All other prior non‐psoriasis concomitant treatments must be on a stable dose for ≥ 4 weeks before initiation of study drug Previous exposure to secukinumab or any other biologic drug directly targeting IL‐17 or the IL‐17 receptor Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a woman after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) Women of childbearing potential, defined as all women physiologically capable of becoming pregnant unless they use 2 effective forms of contraception during the study and for 16 weeks after stopping treatment Men with a female partner of childbearing potential defined as all women physiologically capable of becoming pregnant unless they use 1 effective form of contraception during the study and for 16 weeks after stopping treatment Active systemic infections during the last 2 weeks (exception: common cold) prior to initiation of study drug and any infections that recur on a regular basis; investigator discretion should be used for people who have travelled or recently resided in areas of endemic mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for people with underlying conditions that may predispose them to infection, such as advanced or poorly‐controlled diabetes History of an ongoing, chronic or recurrent infectious disease, or evidence of TB infection as defined by a positive QuantiFERON TB‐Gold test (QFT) at screening. People with a positive QFT test may participate in the study if further work‐up establishes conclusively that the person has no evidence of active TB. If presence of latent TB is established, then treatment must have been initiated and maintained according to UK guidelines Known infection with HIV, hepatitis B or hepatitis C at screening or at initiation of study drug
Dropouts and withdrawals
Secu 150 group (13), Secu 300 group (12)
Death: Secu 150 group (1), Secu 300 group (0) Lack of efficacy: Secu 150 group (1), Secu 300 group (2) Participant decision: Secu 150 group (2), Secu 300 group (1) Lost to follow‐up: Secu 150 group (2), Secu 300 group (3) Protocol deviation: Secu 150 group (0), Secu 300 group (1) AEs: Secu 150 group (5), Secu 300 group (3) Others: Secu 150 group (2), Secu 300 group (2)
|
| Interventions |
Intervention
A. Biological: secukinumab 150 mg at day 0 (initiation of study drug) and at weeks 1, 2, 3 and 4, n = 116
Control Intervention
B. Biological: secukinumab 300 mg at day 0 (initiation of study drug) and at weeks 1, 2, 3 & 4, n = 119 |
| Outcomes |
At 16 weeks
Primary outcome
Secondary outcomes
PASI 90 and PASI 75 after 2, 4, 8, 12, 24, 48 and 72 weeks Quality of life at 16 weeks
|
| Notes |
Funding:
Quote (Clinical.Trials.gov): Novartis
Conflict of interest: not stated |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Quote (Clinical.Trials.gov): "Allocation: randomized"
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 (Clinical.Trials.gov): "Masking: None (Open Label)"
Comment: not blinded |
| Blinding of outcome assessment (detection bias)
All outcomes |
High risk |
Quote (Clinical.Trials.gov): "Masking: None (Open Label)"
Comment: not blinded |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Dealing with missing data: not stated but reasonable rate of withdrawal (10%) and number and reason comparable between groups
Results posted on ClinicalTrials.gov: ITT analyses |
| Selective reporting (reporting bias) |
Low risk |
Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01961609)
The prespecified outcomes and those mentioned in the Methods section appeared to have been reported |
