ACR SOTA Symposium: Update on RA Treatment

Rheumatologists gathered from across the country last week to discuss the latest approaches in the treatment of rheumatoid arthritis (RA) and other inflammatory diseases at the American College of Rheumatology’s (ACR) 2018 State-of-the-Art (SOTA) Clinical Symposium held in Chicago, Illinois.

Joan M. Bathon, MD, of the Columbia University Medical Center, provided an overview of different treatment strategies, a summary of currently approved agents and their comparative effectiveness, and some new agents being used in RA treatment.

Treatment Strategies

Bathon encouraged fellow rheumatologists to “treat early and treat hard.” She explained that initiating disease-modifying anti-rheumatic (DMARD) treatment within 6 weeks of diagnosis or recognition of symptoms maximizes damage prevention and minimizes disability. Early treatment combined with “treating hard,” or using the maximal efficacious dose tolerated by the patient, can lead to better outcomes.

In addition, Bathon noted that rapid escalation of a DMARD has also been shown to be more effective in treatment. For example, Bathon recommended escalating a dose of methotrexate to 20 mg per week by week 8 of treatment.

The third strategy Bathon discussed was to treat with a combination of DMARDs when appropriate, as combination therapy has been found to be consistently more effective than monotherapy. “It’s not 1 study that I can think of—there’s so many studies of treatment of RA now, but I don’t remember 1 that doesn’t show that combination therapy isn’t better than monotherapy,” said Bathon.

Comparison of Therapies

Bathon next discussed results from the BeSt study¹, a randomized controlled trial that she explained was “one of the most important studies in the treatment of rheumatoid arthritis from a strategy perspective.” The study, which took place in the Netherlands, looked to evaluate outcomes from 4 different treatment strategies:

• Group 1 received sequential methotrexate monotherapy
• Group 2 received step-up combination therapy
• Group 3 received initial combination therapy
• Group 4 received initial biologic plus methotrexate combination therapy

The goal of the study was to reach a disease activity score (measured in 44 joints) of less than 2.4. If this goal was not achieved by a particular treatment group in 3 months, the treatment was changed. The study found that, at 24 months, the groups were exactly identical in terms of disease activity score despite receiving different therapies. However, Bathon did note that remission was achieved more quickly if initial treatment began with combination therapy.

New Directions in Treatment

A new anti-IL6 monoclonal antibody, sarilumab, was found to be somewhat more efficacious than adalimumab for American College of Rheumatology (ACR) responses in a head-to-head clinical trial.

The safety profile of sarilumab was found to be similar to that of tocilizumab, with the most notable observed adverse event being neutropenia in about 35 patients (n = 582).

Additionally, Bathon presented on sirukumab, an anti-interleukin-6 monoclonal drug that was rejected by the FDA last August due to a higher number of deaths in the sirukumab group compared with placebo in a trial. The causes of these deaths were found to be cardiovascular events, infections, and malignancies.

Finally, Bathon closed with a few statements about biosimilars, explaining the FDA approval process and how they are developed. When asked if biosimilars will become first-line biologic therapies, Bathon said, “Possibly, for patients who are naïve to the bio-originator product in question.”

However, citing the NOR-SWITCH study,² Bathon also stressed that there was no great toxicity or loss of efficacy found when switched from infliximab to CT-P13, an infliximab biosimilar, in the study.

References

1. Goekoop-Ruiterman YPM, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study). Arthrits Rheum. 2005;52(11):3381-3390. doi: 10.1002/art.21405.

2. Jorgensen K, Olsen I, Goll G, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomized, double blind, non-inferiority trial. Lancet. 2017;389(10086):2304-2316. doi: 10.1016/S0140-6736(17)30068-5.