Table 2 Randomized Control Trials Evaluating Intraarticular TNFi for Persistent Monoarthritis in RA
Author, Year, Country | N of RA | Objective (s) | Study Design | Time in Weeks | Primary Outcome | Joints | Results* | Conclusions | Adverse Events |
|---|---|---|---|---|---|---|---|---|---|
Bliddal [13], 2006, Denmark | 38 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, Denmark | 25 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], 2015, The Netherlands | 30, 11 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, Italy | 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, Egypt | 50 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 |