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Table 1 Randomized Control Trials Evaluating Intraarticular Methotrexate for Persistent Monoarthritis in RA

From: Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic review

Year, Country
N of RA Objective (s) Study Design Time
Joints Results* Conclusions Side Effects
Marks [7], 1976,
United Kingdom
unclear allocation distribution
Comparison of IA MTX + hydrocortisone vs hydrocortisone alone Randomized, Single-blind 36 Pain and physician assessment. Not clearly specified. Knee 5 patients in each group felt improvement following injection, 3 patients had objective improvement on knee examination in each group MTX + hydrocortisone was not superior to hydrocortisone alone No adverse events reported, though CBC and LFT’s had been evaluated
Bird [8],
1977, England
42 total, 23 with RA
MTX: 9
Steroid: 14
Comparison of IA MTX with IA triamcinolone hexacetonide by thermography Randomized 3 Thermography Knee The thermographic index improved in the triamcinolone group and was sustained through 3 weeks (0.02 > p > 0.01 at 7 and 14 days) when compared with MTX. More patients rated their pain as improved in the steroid group (p < 0.0005) Triamcinolone was superior to MTX in reducing thermographic indices of injected knee joints Not discussed
Hall [9],
20 total, 15 with RA
MTX: 3
Saline: 4
MTX & saline to one knee apiece: 8
Comparison of IA MTX vs Saline Randomized, Double-blind 12 Clinical assessment; Arthroscopy findings on day 0 and after 12 weeks Knee Clinical measures improved in both groups, though there were not differences between groups. Less synovial inflammation was seen on 3-month arthroscopy regardless of treatment group No benefit of MTX over saline Not assessed
Blyth [10],
Steroid: 27
Steroid + MTX: 28
Steroid + Rifampicin: 27
Comparative study of IA triamcinolone, triamcinolone and rifampicin, and triamcinolone and MTX Randomized,
24 5-point pain scale Knee Triamcinolone + rifampicin resulted in statistically significant pain control at 3 months (p = 0.039), and the percentage of pain free patients was higher (p < 0.001). All groups improved compared to baseline, but no significant differences noted between triamcinolone +MTX to triamcinolone alone Addition of MTX to triamcinolone did not provide any additional relief 11/28 patients had post-injection pain flares with rifampicin. 1 patient who received MTX had mouth ulcers 10 days after injection
Hasso [11], 2004,
United Kingdom
38, 29 with RA
MTX + steroid: 20
Steroid: 18
Comparison of IA MTX + triamcinolone vs triamcinolone alone in knee synovitis Randomized, Double-blind 24 Patient and assessor global assessments of disease activity, knee pain VAS, duration of stiffness, joint circumference Knee Symptoms scores improved significantly in both groups with worsening between week 12–24, but no difference between treatment groups. 9 patients required repeat corticosteroid injections (5 in the triamcinolone group and 4 in the MTX group) The addition of MTX to steroid injection did not improve symptom scores or clinical response compared with triamcinolone alone in chronic knee synovitis 11 patients had mild elevation of liver transaminases, did not clarify treatment group
Mortada [12], 2018,
MTX: 56
Steroid: 44
Comparison of IA MTX vs triamcinolone acetonide Randomized, Single-blind 20 VAS, US findings Ankle, wrist, and elbow Clinical parameters and ultrasound findings improved in both groups by week 8. The clinical improvement continued in the MTX group to week 20, but plateaued in the steroid group (p = 0.04) Repeated IA MTX injections resulted in a decrease of synovitis in medium-sized joints when compared with a single triamcinolone injection 2 participants in MTX group had oral ulcers, 1 had post-injection nausea. 3 in the steroid group had joint flares
  1. CBC complete blood count; LFT liver function tests; MTX methotrexate; N number; RA rheumatoid arthritis; US ultrasound; VAS visual analog scale
  2. *: When not given, p-value was not reported in the study or was statistically not significant