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

Marks [7], 1976,

United Kingdom

12

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],

1978,

England

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],

1998,

Scotland

82

Steroid: 27

Steroid + MTX: 28

Steroid + Rifampicin: 27

Comparative study of IA triamcinolone, triamcinolone and rifampicin, and triamcinolone and MTX

Randomized,

Single-blind

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,

Egypt

100

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