In Updated Draft Evidence Report on RA, ICER Changes Course on Assessing JAK Inhibitors

The Institute for Clinical and Economic Review (ICER), a nonprofit health technology assessment body, has issued an updated report on treatments for rheumatoid arthritis (RA) in which it says that upadacitinib has a marginal clinical benefit over adalimumab. This benefit comes at higher costs, resulting in an "incremental cost-utility ratio falling below commonly cited thresholds."

ICER first published a version of the draft report in September, but the group rescinded it several days later. The initial report suggested that Janus kinase (JAK) inhibitors’ prices might not be justified given their small benefits compared with biologics like adalimumab and emerging biosimilar options for drugs like infliximab. ICER said in a statement that “internal reviewers identified the need to reevaluate some of the assumptions and calculations in the report to better align our economic modeling with how patients transition between these therapies in the real world.”

In the updated model, patients who do not respond adequately to first-line treatment transition to a basket of targeted products rather than to palliative care. The model also assesses cost-effectiveness in the first year of use rather than over a lifetime. The budget impact analysis was updated to consider threshold prices of just 1 of the JAK inhibitors considered (upadacitinib), and it added a 16% loss in efficacy once patients transition out of first line treatment and into the second line.

Three JAK inhibitors—tofacitinib, baricitinib, and upadacitinib—are approved to treat RA, and ICER compared these products to conventional disease-modifying antirheumatic drugs (DMARDs) as well as to adalimumab.

ICER found in its review of clinical data that upadacitinib and tofacitinib generated superior improvements in disease activity, remission, and American College of Rheumatology (ACR) response criteria relative to DMARD therapy at 12, 24, and 48 weeks in targeted-treatment—naïve and mixed patient populations. Improvements in function and disability were also statistically superior for the 2 JAK inhibitors versus DMARDs.

Upadacitinib plus methotrexate was superior to adalimumab plus methotrexate in rates of disease remission, ACR response, change in pain, and improvement in HAQ-DI score at 12 weeks, and in general, these differences were preserved at weeks 24 and 48. In one head-to-head trial, tofacitinib plus methotrexate was not statistically different from adalimumab plus methotrexate in a mostly naïve population. The one head-to-head study of baricitinib plus methotrexate versus adalimumab plus methotrexate was conducted using a dose of baricitinib not approved by the FDA, and was therefore excluded.

With respect to harms, rates of short-term adverse events (AEs) were comparable across all treatments considered. Based on longer-term data, the JAK inhibitors showed comparable safety profiles to one another.

With respect to cost effectiveness, ICER used a model that assumed a treat-to-target approach was adopted and included a 3-month cycle. The incremental cost-effectiveness ratio for upadacitinib versus adalimumab was estimated to be $92,000 per quality-adjusted life-year (QALY). The cost per month in remission while on upadacitinib versus adalimumab was approximately $600. ICER was not able to compare the cost effectiveness of tofacitinib versus adalimumab due to a lack of data, but also said that the use of either adalimumab or tofacitinib compared to conventional DMARDs resulted in “marginally more QALYs at one year, at a higher cost.”

For upadacitinib, the annual potential budget impact to treat the eligible population across wholesale acquisition cost, assumed net price, and 3 cost-effectiveness threshold prices (for $50,000, $100,000, and $150,000 per QALY) did not exceed the $819 million threshold.

On the whole, said ICER, “more comparable data are required on the short and long-term efficacy of the JAK inhibitors. Upadacitinib, for which we have trial-specific data, provided marginal clinical benefit over adalimumab at higher costs, resulting in its incremental cost-utility ratio falling below commonly cited thresholds.”

Value-based price benchmarks were not included in this draft of the report, but will be included in the revised report slated for publication next month.

Notably, the report also contains an assessment of coverage policies in which it reports that most national commercial insurers require prior authorization for tofacitinib, as well as documented inadequate response or contraindication to DMARDs. Several payers have step therapy that restricts tofacitinib, such as requiring the failure of 2 biologics. For baricitinib, all commercial insurers require step therapy.

For biosimilar infliximab and its reference product, ICER said that all national commercial insurers except Aetna had different coverage criteria for the 2 products. While Aetna treats all infliximab products as preferred brands, others prefer the brand-name product. Some payers, like Anthem, require patients to fail reference infliximab before accessing the biosimilar.