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

Abstract

Background Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. Methods A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. Results Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. Conclusion For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.

In-Office Needle Arthroscopic Synovial Biopsy Is an Effective Diagnostic Tool in Patients With Inflammatory Arthritis

“…23 After failure of intra-articular injections of glucocorticoids (in approximately 50% of patients), subsequent treatment options are unclear. 24 The histologic assessment of synovitis may be a source of crucial information regarding the synovial pathology and the response to treatment. In addition to the extent of inflammation, the pathologic evaluation of the synovial sample can help identify biomarkers of disease that can drive the therapeutic decision.…”

Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery

“…MTX is a weak acid drug with pka 4.6 to 5.5, log P of −1.85 and 454 D molecular weight and is chosen as a representative model drug for evaluating drug loading strategies for weak acid drug into exosomes. ( Gaurav et al, 2021 , Sullivan et al, 2021 ). In this research work, MTX is solubilize in phosphate buffer saline pH 7.4.…”

Infliximab microencapsulation: an innovative approach for intra-articular administration of biologics in the management of rheumatoid arthritis—in vitro evaluation

“…The intra-articular administration of infliximab (INF) and other biological DMARDs has been reported, showing promising results in symptomatic relief and a potential delay of the disease progression [ 7 – 9 ], even though no multicentre clinical trial has been carried out to assess its efficacy after its intra-articular administration in solution. Initial findings from various authors indicate that locally administered biological DMARDs have demonstrated high efficacy, sometimes comparable to the local administration of glucocorticoids [ 10 ]. Therefore, in recent years, there has been a growing interest in developing drug delivery strategies that allow for the sustained release of biologics in the joint and its potential clinical applications [ 11 – 13 ].…”