Asaduzzaman 2014.

Methods	Study design: open‐label, randomised, controlled trial of methotrexate vs leflunomide Duration: 6 months Run‐in period: none Location: Bangladesh Number of study centres: 1 Study setting: outpatient Withdrawals: 2 ‐ method of handling missing data not described Study dates: June 2002 to December 2003
Participants	Randomised: n = 32 Completed: n = 30 Baseline characteristics Mean age (SD): Leflunomide ‐ 41.81 years (±13.43) Methotrexate ‐ 37.93 years (±9.34) Sex: 27 males; 3 females Mean disease duration, years (SD): Leflunomide ‐ 3.22 (±2.43) Methotrexate ‐ 2.82 (±2.22) Mean pain (SD) (VAS 10 cm) Leflunomide ‐ 5.06 (±0.68) Methotrexate ‐ 4.93 (±0.27) Mean skin disease (SD) (PASI) Leflunomide ‐ 9.75 (±5.49) Methotrexate ‐ 7.67 (±3.71) Mean patient global assessment (SD) (Likert 1 to 5) Leflunomide ‐ 3.06 (±0.25) Methotrexate ‐ 3.00 (±0) Mean physician global assessment (SD) (Likert 1 to 5) Leflunomide ‐ 3.06 (±0.25) Methotrexate ‐ 3.00 (±0) Mean swollen joint count (SD) (66 joints) Leflunomide ‐ 5.24 (±1.48) Methotrexate ‐ 6.36 (±1.34) Mean tender joint count (SD) (68 joints) Leflunomide ‐ 7.75 (±1.81) Methotrexate ‐ 9.64 (±2.34) Severity of condition: active disease from mild to severe Inclusion: Active psoriatic arthritis (at least 3 swollen and 3 tender joints) Age 18 years or older Normal renal function, liver function, and haematological indices Exclusion: Axial joint involvement Compromised immune function including bone marrow dysplasia Severe uncontrolled infection Concurrent vaccination with live vaccine Patients who received retinoids, PUVA, or ciclosporin within the last 2 weeks
Interventions	Methotrexate group: 10 mg orally in 2 divided doses (12 hours apart) weekly for 6 months. As per the abstract, total dose was 10 mg weekly Leflunomide group: loading dose of 100 mg orally daily for 3 days, then 20 mg orally daily for 6 months Co‐interventions: both groups were allowed to take ibuprofen orally with a maximum allocated dose of 1400 mg (assumed daily) Excluded interventions: not reported
Outcomes	Time points: 6 months Major: Disease response (ACR50, PsARC) ‐ measured for ACR50 and PsARC as response achieved/not achieved, with response achieved indicating benefit PsARC ‐ composite outcome based on 4 assessment measures: patient self‐assessment, physician assessment (improvement = decrease by 1 category; worsening = increase by 1 category), tender and swollen joint counts (improvement = decrease by 30%; worsening = increase by 30%). Treatment response is defined as improvement in at least 2 out of 4 measures, 1 of which must be tender or swollen joint counts, and there can be no worsening in any measure ACR50 ‐ composite outcome based on 7 assessment measures: tender and swollen joint counts, patient and physician global assessments, pain (VAS), ESR or CRP, and results on a functional questionnaire (HAQ). Treatment response is defined by improvement of 50% in both tender and swollen joint counts and in 3 out of 5 other measures Serious adverse events ‐ measured as event/no event, with event indicating harm Withdrawals due to adverse events ‐ measured as event/no event, with event indicating harm Minor: Disease response (ACR20) ‐ measured as response achieved/not achieved, with response achieved indicating benefit ACR20 ‐ composite outcome based on 7 assessment measures: tender and swollen joint counts, patient and physician global assessments, pain (VAS), ESR or CRP, and results on a functional questionnaire (HAQ). Treatment response is defined by improvement of 20% in both tender and swollen joint counts and in 3 out of 5 other measures Pain (VAS 10 cm) ‐ 0 cm for no pain, 10 cm for maximum pain Skin disease (PASI) ‐ scale 0 to 72 (no units), with 0 indicating no psoriasis and 72 indicating very severe psoriasis covering > 90% body surface area Total adverse events ‐ measured as events/no events, with events indicating harm Patient global assessment (Likert 1 to 5) ‐ 1 = asymptomatic, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe Physician global assessment (Likert 1 to 5) ‐ 1 = asymptomatic, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe Swollen joint count (66 joints) ‐ 0 = no swollen joints; 66 = 66 swollen joints Tender joint count (68 joints) ‐ 0 = no tender joints; 68 = 68 tender joints
Notes	Clinical trials registration: not reported Funding: not reported Declarations of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was done using a random number table…32 patients of psoriatic arthritis were taken consecutively and grouped into two by card test"
Allocation concealment (selection bias)	High risk	Allocation concealment was not attempted
Blinding of participants and personnel (performance bias) All outcomes	High risk	"This open, randomized clinical trial…" Open‐label design allowed participants to remain aware of their allocated intervention; no attempt was made at blinding study personnel
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding of outcome assessors was not attempted
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Out of total 32 patients, one patient from each group was excluded from analysis due to lack of follow‐up" This was not accounted for in the reported analysis, although it was considered unlikely to impact the results
Selective reporting (reporting bias)	Unclear risk	This could not be substantiated, as no trial registry record was available for comparison
Other bias	Unclear risk	Baseline characteristics and use of co‐interventions displayed variability between groups, and compliance with study therapy was not reported. It is unclear if this may have influenced the results, particularly in light of the small number of participants