Therapeutic potential of interleukin 6 inhibitors in difficult-to-treat patients with rheumatoid arthritis (results of a retrospective study)

Aim. To investigate predictors of achieving low disease activity (LDA) in patients with difficult-to-treat (DtT) rheumatoid arthritis (RA) and to assess the role of interleukin 6 (IL-6) inhibitors in reaching the target disease activity in this patient population.

Material and methods. Analysis of medical records of 1145 patients with a confirmed diagnosis of RA was conducted. Patients with a follow-up duration of less than 6 months, those who had not undergone conventional disease-modifying antirheumatic drug (DMARD) therapy, and patients later reclassified with a different diagnosis were excluded. In the selected group (n = 966) DtT patients were identified as those with RA who received recommended treatment with conventional DMARD but failed to achieve LDA or remission after therapy with two classes of biologic disease-modifying antirheumatic drugs (bDMARDs) or janus kinase inhibitors (JAKi)/bDMARDs, or had their treatment discontinued due to adverse events. In the DtT group, two subgroups were distinguished: those who achieved LDA after being classified as DtT due to a change in JAKi/bDMARDs and those who did not achieve LDA.

Results. Median duration of the disease in the DtT cohort was 186 months (interquartile range 104–278), and median duration of DtT status at the time of the last observation was 27.8 months (interquartile range 10.2–56.0 months). A total of 484 treatment episodes involving JAKi/bDMARDs among DtP patients were analyzed. Comparison of the group that achieved LDA (LDA+, n = 172; 35.5 %) with the group that did not achieve LDA (LDA–, n = 312; 64.5 %) revealed that the LDA+ was characterized by younger age of RA onset (p = 0.005), later initiation of DMARD (p = 0.005) and JAKi/bDMARDs (p = 0.034) therapies from the onset of RA, and more frequent presentation with stage IV radiological findings per Steinbroker (p = 0.007). Additionally, glucocorticoids were used less frequently at the last visit in the LDA+ group (p = 0.042). Comparison of the frequency of LDA or remission within the DtP cohort revealed no significant differences among classes or individual medications. In the highest percentage of cases, abatacept and IL-6 inhibitors achieved target disease activity (40.5 % and 40.4 % respectively). Among the IL-6 inhibitors, the highest success rates were observed with levilimab (48.0 %) and tocilizumab (41.3 %).

Conclusion. Patients with late-stage RA and pronounced radiological changes show potential for achieving LDA. The administration of abatacept and IL-6 inhibitors as first-line therapies may reduce the likelihood of developing DtT status, and in cases with this status occurs, target disease activity can be achieved in 40.5 % and 40.4 % of cases, respectively.

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