Reich 2016.

Methods	Phase II, randomised, placebo‐controlled, parallel‐arm study Seven centres in France, Germany, the Netherlands, and the UK (community centre clinics) Period of inclusion: 26 April 2011 to 16 April 2014
Participants	Inclusion criteria ≥ 18 years of age Palmoplantar pustulosis > 6 months Palmoplantar pustulosis refractory to topical therapy and standard skin care PPPASI score ≥ 8 with ≥ 10% of the palms/soles involved Exclusion criteria Pregnancy Allergies to the active ingredient or any excipients Severe disease Not meeting psychological criteria Baseline data: participants were randomised to alitretinoin 30 mg once daily (n = 24) or placebo (n = 9) for up to 24 weeks Mean age, years: 48.8 ± 14.9; 49.0 ± 16.3 Male/female: 10/14; 4/5 Mean PPPASI score: 18.5; 21.1 Total pustule count: 106; 82.7 Proportion of participants with psoriatic lesions elsewhere: not specified Withdrawal: 10 (lack of efficacy: n = 4; adverse event: n = 3; reason not specified: n = 3); 3 (lack of efficacy: n = 2; adverse event: n = 1)
Interventions	Intervention 1 A: alitretinoin 30 mg once daily PO (24 participants) Intervention 2 B: placebo (9 participants) Co‐interventions: none Duration of treatment: 24 weeks
Outcomes	Primary outcome Palmo‐Plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Secondary outcomes % change from baseline in the mPASI (modified PASI) % of participants with ≥ 50% or 75% improvement in PPPASI or mPASI Change in pustule count on the palms and soles Change in the Nail Psoriasis Severity Index and safety Tolerability
Notes	This study was funded by Stiefel, a GSK company, and Basilea Pharmaceutica Deutschland GmbH NCT01245140
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned to treatment by use of a computer‐generated randomisation code, and were assigned a patient number sequentially in order of enrolment" Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote: "Patients were assigned to treatment by use of a computer‐generated randomisation code, and were assigned a patient number sequentially in order of enrolment. Alitretinoin and placebo had indistinguishable physical characteristics and were provided in packaging that did not reveal the study product identity" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "double‐blind placebo‐controlled" Comment: we consider blinding at low risk for trial vs placebo with no obvious clinical adverse events or known specific taste of experimental drug
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "double‐blind placebo‐controlled with no major side effects" Comment: we consider blinding at low risk for trial vs placebo with no obvious clinical adverse events or known specific taste of experimental drug
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "The full analysis set (used for analysis of all efficacy end points) included all patients in the safety population with at least one efficacy assessment" Comment: even though there were 13 dropouts, the full analysis set (used for analysis of all efficacy endpoints) included all participants in the safety population with at least 1 efficacy assessment. In the alitretinoin group, 10 dropouts (lack of efficacy: n = 4; adverse event: n = 3; reason not specified: n = 3); in the placebo group, 3 dropouts (lack of efficacy: n = 2; adverse event: n = 1)
Selective reporting (reporting bias)	Low risk	Comment: the study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes of interest in the review have been reported in the a pre‐specified way