Is It Better to Switch or Cycle in the Treatment of Rheumatoid Arthritis?

JAK Inhibitors in the Treatment of Rheumatoid Arthritis

The latest group of drugs for the therapy of rheumatoid arthritis (RA) are Janus kinase (JAK) inhibitors. The European Medicines Agency (EMA) has so far approved tofacitinib, baricitinib, and upadacitinib from this category for the indication of RA. In the Czech Republic, their use is covered by public health insurance for patients with high disease activity who do not respond sufficiently to therapy with conventional disease-modifying drugs (csDMARDs: methotrexate, leflunomide, sulfasalazine) or biological treatment.

The procedure in case of the need to change therapy due to the ineffectiveness of the current treatment is not uniform and depends on the physician's judgment and the patient's preferences. A retrospective cohort study based on data from selected US health insurance companies evaluated the impact of various therapy changes in non-responders to one drug from the group of biological treatments.

Study Proceedings

First, patients who were newly prescribed either tofacitinib or a TNF-α inhibitor (etanercept or adalimumab) were identified. From these, those who were monitored for at least 12 months before starting this medication and who had previously been given only one DMARD, which was adalimumab (ADA) or etanercept (ETN), were selected.

After 12 months of monitoring, treatment persistence without more than a 60-day treatment gap or therapy change, treatment duration, effectiveness estimated using validated algorithms based on insurance outcomes, and changes in expenses related to rheumatoid arthritis treatment were evaluated.

Findings

Of the 740 patients thus selected, 549 switched from ADA or ETN to tofacitinib, and 191 changed therapy from ADA to ETN or vice versa. Patients who switched from ADA to tofacitinib, compared to those who cycled from ADA to ETN, achieved a significantly higher rate of treatment persistence during the one-year follow-up (50.5 vs. 36.7% of patients, p = 0.030) and also remained on treatment for a longer duration (239 ± 135 days vs. 204 ± 133 days; p = 0.039). The proportion of effectively treated patients in this group was also significantly higher, primarily due to higher adherence to treatment without the need to add a new csDMARD (77.0 vs. 65.8% of patients; p = 0.043) or without switching to another targeted DMARD (77.0 vs. 64.6%; p = 0.025).

Increasing the dose of the drug was necessary in a significantly smaller number of patients who switched from ETN to tofacitinib compared to patients who switched from ETN to ADA (4.2 vs. 18.7%; p < 0.0001). A numerically larger proportion of patients switched to tofacitinib persisted on treatment, were effectively treated, and did not experience the addition of a new csDMARD.

Expenses related to rheumatoid arthritis were significantly lower in patients treated with tofacitinib compared to patients cycled from ADA and ETN.

Summary and Conclusion

The study results indicate that patients who switched from a TNF-α inhibitor to tofacitinib achieved higher treatment persistence, treatment effectiveness, and lower increases in costs associated with the treatment of rheumatoid arthritis compared to those who changed therapy within the TNF inhibitor group.

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Source: Harnett J., Smith T., Woolcott J. et al. Impact of TNF inhibitor cycling with adalimumab and etanercept vs switching to tofacitinib. Arthritis Rheumatol 2019; 71 (suppl. 10): abstract no. 1426.