Unguided intra-articular injection of betamethasone in small and large peripheral joints in patients with early rheumatoid arthritis results in rapid, effective, and long-lasting inflammatory control when used in combination with systemic medication, according to findings from a 2-year "treat to target" study.
Dr. Merete Lund Hetland, an associate professor at the University of Copenhagen and consultant in rheumatology, said in an interview that "unguided intra-articular injections should be used much more in routine care of early RA, not only in the large joints, but also in smaller joints such as proximal interphalangeal and metacarpophalangeal joints.
"The study was a ‘treat-to-target’ study, aiming at complete inflammatory control [that is, no swollen joints] using conventional DMARDs [disease-modifying antirheumatic drugs] together with intra-articular injections with betamethasone," she added.
The results are part of the CIMESTRA (Cyclosporine, Methotrexate, Steroid in RA) trial, which showed that "continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal" (Ann. Rheum. Dis. 2008;67:815-22; Arthritis Rheum. 2006;54:1401-9
The study investigated the short- and long-term efficacy of unguided intra-articular injections with betamethasone. Investigators determined the effect of repeated injections on pathology visible on MRI, anti–cyclic citrullinated peptide (anti-CCP) antibodies, and IgM-rheumatoid factor status.
For the study, 160 patients with early RA (duration less than 6 months) received intra-articular betamethasone in a maximum of four swollen joints at each visit. They received the injections at 2-week intervals for 8 weeks, then every 4 weeks in combination with step-up DMARDs during 2 years.
In all, 1,373 unique joints, including wrists, knees, shoulders, ankles, elbows, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints, were injected; 531 joints were injected a second time, and 262 a third time.
The patients were treated with methotrexate as monotherapy or in combination with cyclosporine.
Short-term efficacy was assessed by EULAR good-response criteria. Long-term efficacy was assessed by Kaplan-Meier plots of joint-injection survival.
After the first year, 62.3% of the joints that were injected at baseline had not relapsed. After 2 years, 55.5% of the injected joints had not relapsed. All joint areas had good 2-year joint injection survival, which was highest for the PIP joints (73.7%). The 2-year joint response was higher for first injections (56.6%) than for second (43.4%) and third injections (31.3%).
The average total dosage of betamethasone injected after 2 years was 11 mL.
Adverse events were mild and transient, with injections being well tolerated.
A high MRI synovitis score for MCP joints and anti-CCP negativity were associated with poorer joint-injection survival, whereas C-reactive protein and IgM-RF were not, according to the study.
Limitations of the study included the fact that "patients also were treated with DMARDs. Thus, after 6-8 weeks, the effect of DMARD treatment intermingled with the effect of steroids. However, this also reflects real-life practice," said Dr. Hetland.
A new study is underway in which they will investigate "the efficacy of joint injections in patients with early RA receiving TNF [tumor necrosis factor] inhibitor treatment," she added.
"We expect to present 1-year data at the ACR [in Chicago in 2011]."
The study was funded by the Danish Arthritis Foundation. Novartis, Pfizer, and MSD Pharmaceuticals provided study drugs and an independent Good Clinical Practice monitor. Dr. Hetland has received grants and/or honoraria from the Danish Arthritis Association, Abbott, Pfizer, Bristol-Myers Squibb, MSD, UCB, and Roche.