Medical need

Rheumatoid arthritis (RA) is usually treated initially with a conventional synthetic disease-modifying antirheumatic drug (csDMARD), most commonly methotrexate. If the treatment target is not achieved, current treatment recommendations support escalation to biological DMARDs or, after individual benefit-risk assessment, targeted synthetic therapies such as JAK inhibitors.

Despite major advances in RA treatment, a substantial proportion of patients experience inadequate response, loss of response or intolerance. Up to 40% of patients may respond inadequately to an initial TNF inhibitor. Following treatment failure, patients may switch within the same therapeutic class or to a treatment with a different mechanism of action.

Several distinct therapeutic mechanisms are already available in RA, including TNF and IL-6 inhibition, B-cell depletion, modulation of T-cell co-stimulation and JAK inhibition. Nevertheless, sustained disease control and remission remain difficult to achieve for many patients, supporting the continued need for effective therapies acting through novel biological targets.

The problem with current RA Treatments

Despite substantial progress in the treatment of rheumatoid arthritis, many patients do not achieve sufficient or sustained disease control. Treatment failure, loss of response and adverse effects may require patients to switch between therapies, sometimes repeatedly.

Studies have shown that sustained remission remains difficult to achieve, with fewer than one in four patients achieving sustained remission according to stringent remission criteria in a large Swedish registry study.

Although several therapeutic mechanisms are available, new treatment options targeting different biological pathways are needed to improve long-term outcomes for patients with RA.

Safety considerations with current treatments

Safety profiles differ between available RA treatments. Several biological DMARDs carry FDA Boxed Warnings, including for serious infections, while JAK inhibitors carry additional warnings concerning malignancy, major cardiovascular events, thrombosis and mortality.

Almost every drug on the market targets the same three pathways
— TNF, IL-6 and JAK.

A patient who fails those is cycling through variations on one theme. What the field needs is not another TNF inhibitor — it needs a different target.