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Table 2 Randomized Control Trials Evaluating Intraarticular TNFi 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 Adverse Events
Bliddal [13], 2006,
TNFi: 18
Steroid: 21
Comparison of IA etanercept vs methylprednisolone Randomized, Double-blind 4 VAS Elbow, wrist and knee Within-group analysis suggested that methylprednisolone trended towards stronger improvements from baseline though there was no statistical difference between VAS scores in the two groups No statistical difference between methylprednisolone and etanercept, though methylprednisolone had a larger within-group benefit 1 patient developed atrial fibrillation after steroid injection, 1 patient in the Etanercept group developed a skin eruption lasting 2 months
Boesen [14], 2008,
TNFi: 13
Steroid: 12
Comparison of IA etanercept vs methylprednisolone Randomized, Double-blind 4 MRI and US findings, swollen target joint score, tender target joint score, physician VAS Wrist Clinical measures of swollen target joint score, tender target joint score, and VAS improved over 4 weeks though there was no statistical difference between the groups; no difference between groups on imaging outcomes IA etanercept was not superior to methylprednisolone on MRI or US-Doppler imaging  
Roux [15], 2011, France 34
TNFi: 17
Steroid: 17
Comparison of IA etanercept vs corticosteroid injections Randomized, Double-blind 24 Target joint pain Elbow, wrist, knee, and ankle No statistical difference in VAS or HAQ scores between the 2 groups, though they both showed improvement from baseline Both groups showed improvement without significant difference between the treatments 1 episode of phlebitis in the Etanercept group
Aalbers [16],
The Netherlands
with RA
TNFi: 22
Placebo: 9
Comparison of IA etanercept vs placebo Randomized, Double-blind 6 Composite change index based on VAS, clinical assessments, joint swelling + functional disability, patient global assessment and provider global assessment MCP, knee and ankle Etanercept improved the composite change index statistically for the first 2 weeks after injection compared with placebo
(p < 0.001)
IA etanercept appeared to be an effective strategy, at least transiently, with minimal side effects Mild and transient flu-like symptoms and GI complaints occurred in 32% of Etanercept patients and 25% with placebo (P = 0.55)
Carubbi [17], 2016,
82 total, 41 with RA
TNFi: 20
Steroid: 21
Comparison of IA TNFi (Infliximab, Etanercept, or Adalimumab) vs corticosteroid Randomized, Single-blind 52 VAS improvement and safety Shoulder elbow, wrist, MCP, PIP, hip, knee There was an improvement greater than 20% for jVAS of involved joint pain in patients injected with TNFi. In RA patients (p < 0.001 for all time points) IA TNFi was well-tolerated and resulted in at least equal efficacy compared with IA steroids Temporary soreness at the injection site
Salem [18], 2020,
TNFi: 25
Steroid: 25
Comparison of IA etanercept vs methylprednisolone Randomized 12 DAS28, MHAQ functional assessment, VAS, lab and US findings Knee, wrist, ankle, elbow VAS and clinical scores improved in both groups. The etanercept group had a statistically greater improvement over steroids in week 1 VAS and tenderness score (p = 0.007, p = 0.008 respectively); this reversed, and the steroid group was significantly more improved than the etanercept group at 12 weeks (p = 0.001, 0.005 respectively) Comparable improvements seen between the IA etanercept and methylprednisolone groups Temporary localized pain in one etanercept patient
  1. DAS28 disease activity score 28; GA global assessment; HAQ health assessment questionnaire; IA intra-articular; MCP metacarpophalangeal; MHAQ modified health assessment questionnaire; MRI magnetic resonance imaging; PIP proximal interphalangeal; PsA psoriatic arthritis; RA rheumatoid arthritis; TNFi tumor necrosis factor inhibitor; US:ultrasound; VAS visual analogue scale; jVAS joint visual analogue scale
  2. *: When not given, p-value was not reported in the study or was statistically not significant