Background/Purpose: Tofacitinib was the first Janus kinase (JAK) inhibitor FDA approved for the treatment of RA in November 2012, five- and one-half years later, baricitinib, also received approval.  The oral delivery of JAKs make them particularly appealing treatment options for patients with moderate to severe disease, however, many patients still receive a TNF-α-inhibitor in the first-line biologic/JAK treatment setting. With two JAKs available and several JAK entities in clinical development, it is important to understand how US rheumatologists are prescribing these agents in relation to biologics, why patients typically discontinue first-line JAK treatment, and how likely rheumatologists are to prescribe consecutive JAK inhibitors to their RA patients.

Methods: An independent market analytics firm collaborated with US rheumatologists (n=101) to conduct analysis of the RA Market. Data were collected via an online survey fielded in May 2019 and included physician demographics and attitudinal survey responses.

Results: US Rheumatologists estimate that half of their biologic/JAK-treated RA patients are on a first-line agent.  Despite increased advanced treatment options available, TNF-α-inhibitors continue to dominate first-line advanced systemic therapy, with rheumatologists reporting 79% are prescribed a TNF-α-inhibitor prior to JAKs or other biologics. Just 8% are treated with a JAK-inhibitor prior to biologic therapy, though use does significantly increase with each consecutive line of therapy, and 18% and 26% of all second- and third-line biologic/JAK-treated RA patients, respectively, are prescribed either tofacitinib or baricitinib. The most common reasons for pre-biologic JAK discontinuation include primary efficacy failure/lack of initial response (41%) and secondary efficacy failure/waning efficacy over time (29%).  Aspects such as tolerability, safety concerns, and patient adherence also play a role, albeit to a much lesser degree than those related to efficacy. When first-line JAK patients discontinue due to primary efficacy failure they are the most likely to be prescribed a TNF-α-inhibitor in the second-line setting.  Of note, one-quarter of first-line JAK patients who have discontinued due to primary efficacy failure will bypass TNF inhibitor treatment and move from a JAK to the IL-6 inhibitor, tocilizumab.  Only 6% report that when a lack of initial response is at play, they will prescribe a consecutive JAK-inhibitor; however, if a patient discontinues due to waning response, respondents are more likely to cycle JAKs, with 11% of all secondary JAK failures prescribed another JAK. When JAK cycling occurs, it is most often attributed to patient preference for oral treatments.

Conclusion: With two JAK inhibitors currently available in the US RA armamentarium, and several late stage JAKs in development, the relationship and typical treatment protocol for JAK use is important to understand.  Current pre-biologic use of JAKs is limited at just 8% of all first-line patients, though use of the class does increase in later lines of therapy.  Currently, rheumatologists’ propensity to cycle consecutive JAK therapies for the treatment of RA is minimal, and when it does occur, is most commonly patient-driven.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pre-biologic-use-of-janus-kinase-inhibitors-for-the-treatment-of-rheumatoid-arthritis-in-the-united-states/