Willkens 1984.

Methods	Study design: double‐blind, randomised placebo‐controlled trial of methotrexate vs placebo Duration of study: 12 weeks Run‐in period: none Location: United States of America Number of study centres: up to 10 based on author affiliations, although not specifically reported Study setting: outpatient Withdrawals: 4 ‐ method of handling missing data not reported Dates of study: not reported
Participants	Randomised: n = 37 Methotrexate ‐ n = 16 Placebo ‐ n = 21 Completed: n = 33 Methotrexate ‐ n = 14 Placebo ‐ n = 19 Baseline characteristics Mean age, measure of dispersion not reported: Methotrexate ‐ 47 years Placebo ‐ 44 years Sex: Methotrexate ‐ 7 males, 9 females Placebo ‐ 8 males, 13 females Disease duration, measure of dispersion not reported: Methotrexate ‐ 103 months Placebo ‐ 159 months Severity of condition: Methotrexate ‐ mild 5, moderate 10, severe 1 Placebo ‐ mild 2, moderate 16, severe 3 Diagnostic criteria: rheumatologist‐diagnosed PsA Inclusion criteria: Age between 20 and 70 years Established diagnosis of psoriasis, with confirmation by dermatology consultation or by skin biopsy as required Psoriatic arthritis based on the following criteria: (1) classic psoriatic arthritis in which DIP joints were predominantly involved; (2) clinical appearance of rheumatoid arthritis, but with persistently negative tests for rheumatoid factor (< 1:80), absence of rheumatoid nodules, and presence of psoriasis; (3) arthritis mutilans Patients were not excluded if sacroiliac or spinal involvement was present Active arthritis involving 3 or more joints for a period of 6 months Unsuccessfully treated (previous therapies had not been adequately effective or toxicity had occurred) with anti‐inflammatory doses of aspirin or other NSAIDs Not taking gold, steroids, or amino‐quinoline drugs for at least 2 months Exclusion criteria: Ultraviolet treatment within a month of starting treatment or during the trial Pregnant or nursing mothers Conditions, medical or surgical, that would compromise absorption, metabolism, or excretion of methotrexate (e.g. a confirmed diagnosis of active peptic ulcer disease, chronic disease of the GI tract, such as inflammatory bowel disease) Clinically detectable liver disease Elevation of hepatic enzymes or serum bilirubin to a level 2× upper limit of normal Positive hepatitis B surface antigen Significant renal disease (SCr > upper limit of normal, or creatinine clearance < 50 mL/min) Regular or sporadic alcoholic beverage intake of more than 14 ounces per week (100 proof liquor or equivalent) Concurrent therapy with any other experimental drug Previous therapy with methotrexate or other cytotoxic drug Pre‐existing bone marrow hypoplasia Active infection, except for minor self‐limited infection Recent major surgery Insulin‐dependent diabetes mellitus Over‐obesity as determined by the investigator Primary diagnosis of ankylosing spondylitis Thrombocytopaenia (defined as platelet count < 150,000) and/or leucopaenia (defined as total white cell count < 3500 cells/mm³ or polymorphonuclear cell count < 1500 cells/cm³) History or presence of malignancy
Interventions	Methotrexate group: oral methotrexate tablets given as 2.5 mg every 12 hours for 3 consecutive doses each week. This could be increased to 15 mg/week after 6 weeks, with 3 doses of 5 mg taken at 12‐hour consecutive intervals Placebo group: placebo tablet was given every 12 hours for 3 consecutive doses each week Concomitant medications: constant background therapy of either ibuprofen (1600 to 2400 mg/d) or indomethacin (75 to 200 mg/d), which started at least 2 weeks before entry into the trial Analgesic therapy with acetaminophen or propoxyphene was allowed Excluded medications: not reported
Outcomes	Time points: 3 months Major: Serious adverse events ‐ measured as events/no events, with events indicating harm Withdrawals due to adverse events ‐ measured as events/no events, with events indicating harm Minor: Total adverse events ‐ measured as events/no events, with events indicating harm N.B. Efficacy of treatment was based on tender joint count, swollen joint count, grip strength, physician global assessment, patient global assessment, and psoriasis involvement. These outcomes were reported within the trial as median differences between baseline and conclusion for each treatment group. No measures of dispersion were provided. Baseline measures for each outcome were not reported. Study authors were contacted but were unable to provide further details (such as mean (SD), or median (IQR), for each outcome and for each group at baseline and at 3 months) because original data were permanently unavailable
Notes	Clinical trials registration: not reported Funding: supported by grants from the National Institute of Arthritis, Metabolism and Digestive Diseases contract no. 6‐2218, the Public Health Service Research #RR‐00064 (from the Division of Research Resources), and an Arthritis Foundation Clinical Research Center to the University of Tennessee Center for Health Sciences Declarations of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Sequence generation was done via a randomised schedule, but this was not described in any detail
Allocation concealment (selection bias)	Unclear risk	Allocation concealment procedures were not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Participants received a placebo MTX tablet, although study authors did not describe the appearance of the 2 tablets, nor did they describe blinding procedures
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding procedures were not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Handling of incomplete outcome data was not described
Selective reporting (reporting bias)	Unclear risk	Several outcomes were reported in a manner that data could not be extracted
Other bias	Unclear risk	Baseline imbalances may favour the treatment group Co‐interventions were the same between groups, although their usage was not reported Compliance was considered acceptable, as a tablet count occurred at each visit Overall this trial was judged to have unclear risk of bias for these results