On April 7, 2017, the Institute for Clinical and Economic Review (ICER) published its final report, titled, Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value.1 The stated objective of the report was to assess the comparative clinical effectiveness of the targeted immune modulators (TIMs) used to treat patients with moderate to severe active rheumatoid arthritis (RA), as well as the comparative value of these therapies in terms of cost effectiveness.1
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A Flawed Report?
The good news from the report: TIMs are highly effective in treating moderate to severe RA. Their life-changing effects for RA patients were emphasized by ICER President Seven D. Pearson, MD, in a press release accompanying the report’s publication.2
However, the report also found that none of the TIMs was considered cost effective based on the methodology used in the report.
This latter finding is generating considerable concern among rheumatologists and patient advocacy groups who fear that any documented analysis showing the use of these expensive drugs is not cost effective may interfere with patient access to these drugs and may, ultimately, be used to set policy and formulary decisions.
“The ICER report is basically flawed in that the methodology and analysis do not cohere with the ACR and EULAR guidelines on RA treatment with TIMs,” says Elizabeth A. Tindall, MD, a rheumatologist from Rheumatology Consultants of Oregon LLC, who reviewed and commented on drafts of the report before its final publication. “This would limit patient access to many RA therapies.”
Guy Eakin, PhD, senior vice president of scientific strategy for the Arthritis Foundation (AF), acknowledged the flaws in the methodology used in the report, specifically questioning the patient population used in the study to generate the cost-effectiveness analysis, which he thinks is not representative of the true patient population with RA. However, Dr. Eakin, who worked closely with ICER in developing the report, commended the ICER report for its transparency in tackling the difficult issue of cost of these expensive medications.
Report Basis, Findings, Recommendations
The ICER report was based on an analysis of data from 67 randomized clinical studies and 17 observational studies on the use of 11 TIMs (or biologics) either as monotherapy or in combination with conventional disease-modifying anti-rheumatic drugs (DMARDs) to treat patients with moderate to severe RA. Included in the analysis were nine TIMs approved by the Food and Drug Administration (FDA) for RA, as well as two investigational TIMs still awaiting FDA approval (Table 1).1
|Table 1: Targeted Immune Modulators Included in the ICER Report|
|High Certainty of FDA-Approved TIMS||· Adalimumab
· Certolizumab pegol
|Investigational TIMs (awaiting FDA approval)||· Sarilumab
The report found that all TIMs provide a substantial net benefit when combined with conventional DMARDs—compared with DMARDs alone—in people with moderate to severe RA. When looking at head-to-head studies that compared the clinical effectiveness between specific TIMs (adalimumab was the most commonly used TIM as comparator), the report found more modest benefits between the TIMs (Table 2). For TIMs that were not compared in head-to-head studies, the report stated that there was insufficient evidence to differentiate the therapies.1
|Table 2: Head-to-Head Comparisons of TIMs: Findings|
|Monotherapy Regimens||Incremental or better net benefit found with sarilumab monotherapy and intravenous tocilizumab monotherapy compared to adalimumab monotherapy.|
|Combination Regimens (with Conventional DMARDs)||Comparable net health benefits found between regimens involving tofacitinib, subcutaneous abatacept, certolizumab pegol and etanercept, and regimens involving adalimumab plus methotrexate.
Comparable or better net health benefit found in a single trial of combination therapy with baricitinib compared with adalimumab.
When looking at the comparative value among TIMs, the report found that none of the 11 TIMs were considered cost effective based on a formula that establishes a reasonable value on a therapy when the cost per quality-adjusted life year (QALY) is between $50,000 and $150,000. All of the TIMs were found to be above that cost threshold.3
To calculate cost, the report used a model based on a sequential treatment pattern in which patients who fail to respond (based on ACR20) to a TIM after six months can switch to another TIM up to three times. After the third failure, the fourth and final treatment option is called palliative care—meaning treatment with conventional DMARDs.1
Finally, the report provided a number of key policy recommendations:
- Consider including in prior authorization processes the requirement that conventional DMARD therapy dosing be optimized before initiating TIM therapy;
- If step therapy protocols require patients to fail one or two TNFα inhibitors before switching to another TIM, develop a quick and transparent exception process for specific situations;
- Payers should reach out to providers to learn from their experience with prior authorization to streamline and improve the process;
- Reconsider step therapy if pricing becomes better aligned with clinical value;
- Negotiate better rebates, and share savings with patients;
- Increase transparency around the role of discounting and rebate practice in formulary design; and
- Design innovative risk-sharing payment agreements, including pay-for-performance contracts, value-based contracts and indication-specific pricing.
Specific Concerns of Cost-Effectiveness Findings
Although the recommendation includes a number of policy recommendations encouraging patient access, Dr. Tindall remains concerned that the cost-effectiveness conclusions of the ICER report will be used by insurance companies to justify restricted formularies, step therapy, medication switching and coverage denials for many FDA-approved RA therapies. “This will make it more difficult for patients to access the care they need,” she says.
Specifically, she took aim at the model framework used to calculate cost, emphasizing that it is inconsistent with the recommendations of the 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis, which recommends a treat-to-target strategy.
“In the clinic, we measure disease activity, not an ACR20 response, to determine appropriate treatment,” she says, adding that she is also concerned about the limited treatment options allowed in the report and, especially, the final palliative care sequence.
“The ACR 2015 RA [guideline does] not limit treatment to three TIMs, nor are patients placed on palliative care/conventional DMARD treatment after three switches,” she wrote in a letter to ICER prior to the final publication of the report. “The ideal target should be low disease activity or remission, as determined by the clinician and the patient,” she said.
ACR President Sharad Lakhanpal, MD, MBBS, also expressed concern over the potential for limited access to appropriate care based on the report’s findings. While acknowledging the importance of comparative effectiveness research (CER), he stresses the importance of not limiting treatment options for patients. “Ideally, CER would highlight the need for multiple treatment options to address heterogeneous groups of patients with individual and unique co-morbidities,” he said in a press release.4 “The ACR is concerned that the ICER report, while based on a commonly used method to assess cost effectiveness, provides insufficient information on model structure and validation.”
Dr. Tindall also expressed concerns over the calculations used to assess the cost of TIMs, highlighting the failure in the report to include rebates/vouchers, infusion facility costs, direct out-of-pocket costs, time off work for infusion, monitoring costs and office vs. hospital charges.
“If you’re talking about cost, why don’t you really talk about cost?” she asks, adding that the report fails as a true cost-effective research analysis due to its failure to include all relevant costs.
Looking at this in a different way, Louis Tharp, executive director and co-founder of CreakyJoints, emphasizes the need to look at cost in terms of the benefit of controlling disease. “We believe it is imperative that such a report incorporate the economic benefits to society derived from sustained worker productivity and quality of life that results from the use of biologics,” he says. “The report is inexcusably flawed with this value omitted. The report relies on short-term clinical trial data, ignoring the nearly two-decades-old benefits of substituting legs for wheelchairs.”
How the ICER report may be used by payers and to, perhaps, set policy is not yet known. The ICER report on RA is the latest among other ICER final reports recently published in the area of rheumatology, including final reports on psoriasis published in December 2016 and multiple sclerosis published in February 2017. There is also an osteoporosis report due in June.
Although it is too early yet to know how these reports may be used, concern is building on their potential use to set policy and fundamentally alter patient access to optimal care.5
What everyone appears to agree on is that physicians and patients both need to get and stay involved in the conversation to ensure that patients retain access to important medicines while efforts, such as those taken by ICER, address the high cost of healthcare delivery.
Mary Beth Nierengarten is a freelance medical journalist based in Minneapolis.
- Institute for Clinical and Economic Review (ICER). Targeted immune modulators for rheumatoid arthritis: Effectiveness & value. Evidence Report. 2017 April 7. https://icer-review.org/wp-content/uploads/2016/08/NE_CEPAC_RA_Evidence_Report_FINAL_040717.pdf.
- Institute for Clinical and Economic Review (ICER). Institute for Clinical and Economic Review’s final report on treatments for rheumatoid arthritis finds evidence inadequate to distinguish overall benefits between newer agents and prices too high in relationship to the clinical value provided to patients. Press release. 2017 April 7. https://icer-review.org/announcements/ra-final-report.
- Institute for Clinical and Economic Review (ICER). Targeted Immune Modulators for Rheumatoid Arthritis: Effectiveness & Value. Report-at-a-Glance. https://icer-review.org/wp-content/uploads/2017/04/NECEPAC_RA_RAAG_040717.pdf.
- American College of Rheumatology (ACR). Rheumatology community responds to Institute for Clinical and Economic Review’s (ICER) review of treatments for rheumatoid arthritis. 2017 April 7. http://www.rheumatology.org/About-Us/Newsroom/Press-Releases/ID/804/Rheumatology-Community-Responds-to-Institute-for-Clinical-and-Economic-Reviews-ICER-Review-of-Treatments-for-Rheumatoid-Arthritis.
- Durie BGM. ICER Report: Could a flawed approach to cost-effectiveness assessment put patients at risk? Dr. Durie’s Blog. IMF. 2016 April 24. http://brianduriemd.myeloma.org/?q=icer-report.