-Analyses of evidence on comparative effectiveness raise questions about current step therapy protocols, while net prices for all TIMs found to be too high in proportion to their added clinical value for patients-

Boston, Mass., March 10, 2017 – The Institute for Clinical and Economic Review (ICER) has released an Evidence Report assessing the comparative clinical effectiveness and value of targeted immunomodulatory drugs for the treatment of rheumatoid arthritis (RA). This Evidence Report will be the subject of the upcoming public meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC) on March 24, 2017.

The report evaluates the evidence on targeted immune modulators (TIMs), used alone or in combination with conventional disease-modifying anti-rheumatic drugs (DMARDs), as compared to conventional DMARDs alone. It focuses on the clinical effectiveness, potential harms, and comparative value of treating moderately-to-severely active RA in patients who have had inadequate response or intolerance to conventional DMARDs. The review also includes an evaluation of two agents currently under regulatory review for this indication: sarilumab (Kevzara™, Sanofi and Regeneron) and baricitinib (Olumiant™, Eli Lilly and Co.).

“Our report found that many TIMs offer substantial clinical benefit to patients as compared to conventional DMARD therapy alone,” stated ICER President Steven D. Pearson, MD, MSc. “However, our report also concluded that evidence to distinguish the effectiveness among different TIMs is quite limited, and current prices of all TIMs are not well-aligned with the added benefit they provide for patients. These results raise important questions about existing pricing and coverage policies. An important goal of our report and meeting will be to explore these issues and identify actions that can be taken to help improve the effectiveness and the value of care for all patients with RA.”

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, the manufacturers of the drugs, and other stakeholders.

The ICER report reviewed the following agents:

TNF Inhibitors

  • Adalimumab (Humira®, Abbvie)
  • Certolizumab pegol (Cimzia®, UCB)
  • Etanercept (Enbrel®, Amgen)
  • Golimumab (Simponi® and Simponi Aria®, Janssen)
  • Infliximab (Remicade®, Janssen)

CD20- directed cytolytic antibody

  • Rituximab (Rituxan®, Genentech)

T-cell inhibitor

  • Abatacept (Orencia®, BMS)

IL-6 inhibitors

  • Sarilumab (Kevzara™, Sanofi and Regeneron) (currently under FDA review)
  • Tocilizumab (Actemra®, Genentech)

JAK inhibitors

  • Baricitinib (Olumiant™, Eli Lilly and Co.) (currently under FDA review)
  • Tofacitinib (Xeljanz®, Pfizer)

Key Findings of the Evidence Report

ICER’s analysis of clinical effectiveness found that all of the TIMs reviewed represented at least a small net health benefit compared to conventional DMARDs, with most showing substantial improvements. Head-to-head comparisons of some of the TIMs showed comparable or better net health benefit for several agents as compared to the market leader adalimumab when used either as monotherapy or in combination therapy.

To better reflect real-world practice, ICER applied an average discount to the wholesale acquisition cost (WAC) for each drug class to arrive at an estimated net price for use in the cost-effectiveness analyses. The drug discounts were determined from information on net pricing provided by SSR Health. ICER’s analyses concluded that, used in combination with conventional DMARDs, all agents reviewed exceeded commonly cited cost-effectiveness thresholds as compared to use of conventional DMARDs alone, with results ranging from $168,660 (tocilizumab, subcutaneous injection) to $271,749 (tofacitinib) per QALY gained. Compared to the market leader adalimumab, eight TIMs (rituximab, intravenous abatacept, tocilizumab intravenous or injection, certolizumab pegol, golimumab intravenous or injection, and infliximab) were more effective and less costly than adalimumab. Abatacept administered subcutaneously and etanercept were more effective but more costly. Tofacitinib was less effective and more costly.

The report also includes value-based price benchmarks that help to identify the prices at which the cost of the drugs align with the benefit they bring to patients. ICER’s analyses found that the prices of the TIMs reviewed that are currently on the market would need to be discounted anywhere from 29% to 69%, depending on the drug, in order to meet commonly accepted thresholds for cost-effectiveness.

ICER is committed to a transparent public engagement process to ensure that all stakeholders have the opportunity to provide input to the reports and public meetings. After ICER’s Draft Evidence Report was released on January 20th, stakeholders had four weeks to provide comments. ICER staff considered these comments and made revisions to the report. The Evidence Report, as well as the accompanying voting questions, public comments, and ICER’s written response to comments, are available on the ICER website.

The Evidence Report will be the subject of the March 24th public meeting of the New England CEPAC during which the independent council will vote on key questions raised in the report, and a policy roundtable of experts will discuss recommendations to apply the evidence to policy and practice. During the meeting, a limited amount of time will be available for pre-registered stakeholders to provide a brief oral comment on the report. Requests to make an oral comment were accepted during the public comment period on the Draft Evidence Report.

Registration for the in-person meeting is open here. Registration for a live webcast of the meeting is open here.

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.