ICER Issues Final Report and Policy Recommendations on JAK Inhibitors for Rheumatoid Arthritis

— Despite upadacitinib reaching common thresholds for cost-effectiveness when compared to adalimumab, the independent appraisal committee's votes on upadacitinib's long-term economic value were split between "low" and "intermediate" due to concerns about the generalizability of the clinical data to patients in the real world —

— During the policy roundtable, experts expressed frustration over the dysfunctional rebate structure that distorts coverage and access to therapies indicated to treat several inflammatory diseases —

BOSTON, January 9, 2020 - The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report and Report-at-a-Glance assessing the comparative clinical effectiveness and value of JAK inhibitors for treating rheumatoid arthritis (RA). These therapies include upadacitinib (Rinvoq™, AbbVie), tofacitinib (Xeljanz®, Pfizer), and baricitinib (Olumiant®, Eli Lilly), as compared to either placebo or adalimumab (Humira®, AbbVie). ICER's report on these therapies was reviewed at the December 2019 public meeting of the California Technology Assessment Forum (CTAF), one of ICER's three independent evidence appraisal committees.

"Rheumatoid arthritis is a progressively disabling condition, and patients are fortunate to have multiple therapy options — including biosimilars — that effectively slow disease progression," said Pamela Bradt, MD, MPH, ICER's Chief Scientific Officer. "Many economists might expect medicines to become more affordable in an increasingly crowded therapeutic class; however, because the current rebate structure has erected barriers between patients and several emerging RA therapies, traditional market dynamics have been unable to drive down prices. Therefore, while upadacitinib appears to achieve common thresholds for cost-effectiveness when compared to adalimumab, legitimate questions remain about whether or not adalimumab, launched 17 years ago, is fairly priced to begin with."

CTAF Voting on Clinical Effectiveness and Contextual Considerations

During the meeting, CTAF members unanimously voted the evidence was adequate to demonstrate that, when added to a conventional Disease Modifying Antirheumatic Drug (cDMARD), upadacitinib, tofacitinib, and baricitinib all provide a superior net health benefit to cDMARDs alone.

For patients who had experience with biologic treatments for RA, a majority of the panelists found that the evidence is adequate to demonstrate that the net health benefit provided by upadacitinib is superior to that provided by adalimumab (Humira®, AbbVie). The panel also found that the evidence was inadequate to distinguish between the net health benefit of upadacitinib and tofacitinib, and also inadequate to demonstrate that tofacitinib is superior to adalimumab. No evidence exists to compare baricitinib to adalimumab.

Separately, CTAF members voted unanimously that the evidence is adequate to demonstrate that the biosimilar infliximab-dyyb (Inflectra®, Pfizer) is clinically equivalent to its reference biologic infliximab (Remicade®, Janssen).

During their deliberation, panel members also weighed the therapies' other benefits and contextual considerations, particularly noting RA's high severity.

CTAF Voting on Economic Value

After weighing the available evidence on comparative effectiveness and incremental cost-effectiveness, and considering other benefits, disadvantages, and contextual considerations, the CTAF voted on upadacitinib's long-term value for money to the US health system at the treatment's currently estimated net price. Despite upadacitinib achieving common thresholds for cost-effectiveness when compared to adalimumab, the panel's votes were split between "low" and "intermediate" long-term value for money. In explaining the rationale for their votes, several panelists noted that that a significant portion of patients with RA likely would not have qualified for the Phase 3 clinical trial for upadacitinib, raising concerns about the generalizability of the data to the real world.

Due to insufficient head-to-head evidence against adalimumab, the CTAF panel did not vote on the economic value of either tofacitinib or baricitinib.

ICER's economic modeling demonstrated that upadacitinib plus a cDMARD achieves marginally higher quality of life than what is achieved with adalimumab plus a cDMARD, at similar costs. Based on this comparison with adalimumab, ICER's value-based price benchmark range for upadacitinib is between $44,000 and $45,000. This benchmark represents a 25% discount off of upadacitinib's annual list price of $59,860, a suggested discount that is consistent with the rebates we assume the manufacturer is currently offering.

ICER's value-based price benchmarks suggest a price range, net of any discounts and rebates, that aligns fairly with a treatment's added benefits for patients over their lifetime. The ranges reflect commonly cited cost-effectiveness thresholds between $100,000 and $150,000 per Quality-Adjusted Life Year (QALY) gained. New interventions introduced at or below these thresholds help maximize health overall, because they do not contribute to affordability concerns and loss of insurance throughout the health system.

Because upadacitinib does not appear to lengthen patients' lives when compared to adalimumab, ICER did not calculate what price would be needed to reach alternative thresholds based on Equal Value of Life Years Gained (evLYG).

An Important Note About Using Adalimumab as a Comparator

Despite upadacitinib achieving common thresholds for cost-effectiveness when compared to adalimumab, all stakeholders should remember that ICER's 2017 review of treatments for rheumatoid arthritis found that adalimumab itself may be priced above commonly cited cost-effectiveness thresholds. In addition, ICER's 2019 assessment of unsupported price increases found that adalimumab's price increases since 2017 represent the costliest for the US health system among all prescription drugs, and that these increases were not supported by new important evidence of additional benefit.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinicians, patient advocates, and representatives from manufacturers and payers — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • In a dysfunctional market system, in order to protect patients today and improve their future access to innovative therapies, policy makers may need to consider some form of regulatory intervention to ensure that drug prices and price increases do not continue their current upward trajectory, driving prices further from reasonable alignment with the added benefits for patients.
  • Insurers, pharmacy benefit managers, and employers should increase transparency around the role of discounting and rebate practice in formulary design for all interventions, including biosimilars.
  • Policymakers should continue work on alternatives to the current rebate system that will allow the market to reward the competitive advantages of lower-priced, equally effective biosimilar treatment options.

ICER's detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

About ICER 

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER's reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER's reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER's reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER's website.

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