ICER Releases Final Report on JAK Inhibitors for Rheumatoid Arthritis

The Institute for Clinical and Economic Review (ICER), an independent research institute that assesses drugs, tests, and other healthcare technologies, recently released its final report and policy recommendations on the clinical effectiveness and economic value of Janus kinase (JAK) inhibitors for treating rheumatoid arthritis (RA).

ICER reviewed clinical data comparing JAK inhibitors tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq) to conventional disease-modifying antirheumatic drugs (DMARDs) or to the TNF inhibitor adalimumab (Humira).

The final report includes voting results from a December 2019 meeting of one of ICER’s independent evidence appraisal panels, the California Technology Assessment Forum (CTAF), plus policy recommendations from an expert roundtable.

With regard to clinical effectiveness and safety, CTAF votes supported the conclusions of the draft evidence report originally issued in October 2019:

• CTAF members voted there was sufficient evidence DMARD plus upadacitinib, tofacitinib, or baricitinib was superior to DMARD alone in patients who have had an inadequate response to DMARD.
• There was sufficient evidence upadacitinib plus DMARD provided net health benefit compared to adalimumab plus DMARD.
• There was insufficient evidence tofacitinib plus DMARD provided net health benefit compared to adalimumab plus DMARD.
• There was insufficient evidence available to compare net health benefit of upadacitinib and tofacitinib.
• Short-term (6-month) adverse events rates were comparable among all treatments; the most common adverse events were infections, such as upper respiratory infections, bronchitis, and nasopharyngitis. The 3 JAK inhibitors had similar safety profiles in trials lasting 1 year or longer.

In the draft evidence report, ICER’s review of long-term economic value concluded upadacitinib provided “marginal clinical benefit” compared to adalimumab at higher costs, however, meeting commonly cited cost-effectiveness thresholds.

The value-based price benchmark for upadacitinib (vs. adalimumab) to treat the entire eligible population across all prices did not exceed the threshold of $819 million. Discounts of 25% to 26% from the list price of upadacitinib would be required to reach the $100,000 to $150,000 per QALY threshold prices. The estimated cost of upadacitinib vs. adalimumab was $600 per month while in remission; the incremental cost-effectiveness ratio was $92,000 per quality-adjusted life-year (QALY).

Despite meeting cost-effectiveness thresholds, CTAF member votes were split between “low” and “intermediate” long-term economic value for upadacitinib, citing a potential lack of generalizability to the real-world patient population, as the exclusion criteria for the only phase 3 clinical trial on this JAK inhibitor would have excluded “a significant portion” of patients with RA. Insufficient data were available to compare tofacitinib or baricitinib to adalimumab in terms of cost-effectiveness.

ICER cautioned that its economic value model may be complicated by the price of adalimumab, which previous assessments by the organization suggested may be above commonly cited cost-effectiveness thresholds.