ICER Concludes Targeted Immunomodulators Are Overpriced: Advocacy Organizations Express Concern

On April 7, 2017, the Institute for Clinical and Economic Review (ICER), an independent non-profit organization that assesses the effectiveness and value of medications and medical services, released its controversial final report on targeted immunomodulators (TIMs) for rheumatoid arthritis (RA).¹ The report focused on the use of 11 such agents for the treatment of moderately to severely active disease, two of which are investigational and under review by the US Food and Drug Administration (FDA) (Table).^1,2

While ICER’s report was praised by some, it also raised considerable concerns, particularly among patient advocacy organizations and medical associations. Many had sent ICER feedback on its draft report or participated in ICER’s public meeting on RA ahead of the report’s release.

ICER’s final report examines the effectiveness and value of TIMs using clinical trial and observational study data on these agents as monotherapy or in combination with conventional disease-modifying antirheumatic drugs (cDMARDs). While ICER found TIMs to be efficacious overall, producing “statistically and clinically-superior improvements in symptom response, disease activity, radiographic progression, and other important outcomes when compared to cDMARD therapy alone,” none of the TIMs met ICER’s criteria for cost effectiveness, which was set at ≤$150,000 per quality-adjusted life year (QALY) gained.¹

To reach this value-based benchmark, the cost of TIMs would have to be reduced by 29% to 69%, with most agents requiring cuts >45%.¹

Based on these findings, ICER concluded that the “evidence [is] inadequate to distinguish overall benefits between newer agents and [the] prices too high in relationship to the clinical value provided to patients.”³ The findings, which are in keeping with the findings in the draft report, have led to concerns about how this  report could be used by insurers to limit patients’ treatment options.

The Institute for Patient Access (IfPA), a “physician-led research organization dedicated to maintaining the primacy of the physician–patient relationship in the provision of healthcare,” stated in a draft feedback letter that “ICER’s model for calculating cost effectiveness is ill-suited for arthritis treatment.”⁴

IfPA supported this assertion by highlighting several deficiencies in ICER’s methodology for making its value-based calculations.⁴ Many of the concerns expressed in the feedback letter apply to the final report.

A Homogenous Cohort

ICER’s assessment relies on clinical trial and observational study data in patients with moderately to severely active disease and does not account for patients with early disease, experiences in clinical practice, or long-term follow-up. ICER acknowledges these limitations in its report, noting “Modeling a homogeneous RA patient cohort limits the ability to account for the diverse nature of RA treatment. In clinical practice, treatment choice is often based on patients’ individual characteristics and risk factors, which may not be consistent with the model’s sequential treatment pattern.”¹

IfPA’s draft feedback statement notes that “this limitation is significant” and that ICER’s findings are, at best, “applicable only to the population that matches the estimated cohort.”⁴

Similar concern was expressed by the Alliance for Patient Access shortly before the ICER public meeting.⁵ “Population level analytics cannot predict which treatment will work for any individual patient. So these data points should not be used by health plans to override the physician-patient relationship and impede a physician’s ability to determine the best course of treatment for a given patient,” said Brain Kennedy, the organization’s executive director, in a press statement.⁵

The American College of Rheumatology (ACR) supported these concerns in a statement following the release of ICER’s final report.⁶

While the organization stated it actively supports comparative effectiveness research (CER) because it can be a useful tool in decision-making, “Ideally, CER would highlight the need for multiple treatment options to address heterogeneous groups of patients with individual and unique co-morbidities.

Unfortunately, studies that lack long-term follow-up and do not take into consideration patient heterogeneity, co-morbidities, preferences and tolerances must be interpreted within their limitations.”⁶  

Overestimation of Treatment Duration

ICER used a lifetime time horizon to calculate RA treatment duration. It used this model “to reflect the chronic nature of RA,”¹ but this measure significantly overestimates the duration of patients’ treatments, the IfPA noted.⁴ “For many patients, the timeframe used in a clinical setting would vary dramatically from ICER’s assumptions, significantly altering ICER’s cost estimates.”⁴

In ICER’s model, a 55-year-old patient is projected to have a lifetime time horizon of 20 to 25 years and to remain on their medication for that duration, but this is not reflective of clinical practice. “In reality, TIMs are typically first prescribed for a limited timeframe – 6 months, for instance.

Then, if the patient’s arthritis symptoms improve, a doctor will prolong treatment. If patients achieve remission, doctors may slowly phase out the medications,” the IfPA release notes, indicating that this applies to TIMs and cDMARDs.⁴

IfPA suggests ICER would obtain more realistic results by accounting for such shorter timeframes in its base model for determining cost-effectiveness.⁴ The ACR expressed similar concerns with how ICER derived its final cost-effectiveness calculations, noting there is “insufficient information on model structure and validation.”⁶

Quality Measures Not Reflective of Patient Experiences

In determining long-term cost-effectiveness, the ICER draft report used QALY to determine a patient with RA’s quality of life, but as the IfPA noted in its feedback letter, there are many subjective measures of well-being with RA that are not accounted for by using this measure.⁴ Additionally, because QALY was determined solely using the Health Assessment Questionnaire (HAQ), many other important measures were excluded, such as radiographic findings, resulting in a limited picture of patients’ true health quality.⁴

During ICER’s public meeting, which was encouraged by the Arthritis Foundation to enable ICER to better understand patient experiences, several patient advocates expressed their concerns about the draft report and relayed their life-changing experiences with biologics.^7,8 One such advocate, Chantelle Marcial, provided a particularly powerful message by contrasting her experience with that of her mother.⁸ “For decades, patients were overwhelmingly limited to cDMARD therapy such as methotrexate. My mother was an example and she lost the ability to walk. For 25 years, her only options were cDMARDs. Biologics stopped what happened to her from happening to me. Biologics, not methotrexate, took away the wheelchairs.”⁸

Another patient attending the meeting, Anna Legassie, relayed that her biologic therapy enables her to “run Spartan races and live [her] life,” but that she discovered that her insurer does not cover her biologic and that she lives in constant fear that she will eventually be denied treatment.⁷ “Access to my biologic allows me to work and contribute to society economically at the same level or above many healthy people,” she said.⁷

ICER’s final report no longer relies solely on HAQ. It correlates function and disability on HAQ with ACR response and radiographic progression.¹ Nevertheless, it still arrives at the conclusion that TIMs are overpriced for the value they provide patients. Therefore, as noted by CreakyJoints about ICER’s draft report, this final report also “overvalues suppression of symptoms using cMARDs over the longer-term benefits enjoyed by patients who reduce their risk for possible joint degregation by the use of more complex, and more expensive, biologic medicines.”⁸

So What Does ICER’s Report Ultimately Mean for Patients?

It is unclear to what extent ICER’s report might affect patients’ healthcare plans, access to RA treatments, and insurers’ coverage of TIMs. The report is long and complex and many medical organizations, such as the ACR, are still in the process of reviewing it to determine its possible implications. The ACR has promised to provide additional feedback in the coming weeks.⁶

In addition, while ICER’s overall findings have been met with concern, it appears that ICER has taken at least some patient concerns to heart. The final report added several recommendations to payers and pharmacy benefit managers that would benefit patients, such as enabling patients who are stable on effective treatment to remain on that therapy when they change insurers and improving rebate negotiations and sharing those cost savings with patients.^1,8 The hope is that the report will continue to spark a dialogue that will improve patient care, rather than limiting access to much needed treatments.

Table. Targeted Immunomodulators Assessed in the ICER Report

Tumor necrosis factor-alpha inhibitors Adalimumab Certolizumab pegol Etanercept Golimumab Infliximab

T-cell Inhibitor Abatacept

CD20-directed cytolytic B-cell antibody Rituximab

Interleukin-6 receptor inhibitors Approved Tocilizumab Tofacitinib Investigational Baricitinib (delayed April 19, 2017) Sarilumab (anticipated mid-2017)

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References

1. Institute for Clinical and Economic Review (ICER). Targeted immune modulators for rheumatoid arthritis: effectiveness and value. https://icer-review.org/wp-content/uploads/2016/08/NECEPAC_RA_Evidence_Report_Final_040717.pdf. Published April 7, 2017. Accessed April 19, 2017.
2. Business Wire. US FDA issues complete response letter for baricitinib [news release]. www.businesswire.com/news/home/20170414005051/en/U.S.-FDA-Issues-Complete-Response-Letter-Baricitinib. Released April 14, 2017. Accessed April 19, 2017.
3. 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. https://icer-review.org/announcements/ra-final-report. Published April 7, 2017. Accessed April 19. 2017.
4. Institute for Patient Access (IfPA). Feedback on ICER’s Rheumatoid Arthritis Draft Evidence Report. http://allianceforpatientaccess.org/wp-content/uploads/2013/08/IfPA_ICER-Arthritis-Report-Feedback_Feb.-2017.pdf. Submitted February 16, 2017. Accessed April 20, 2017.CreakyJoints.
5. Alliance for Patient Access. Statement from Brian Kennedy, executive director, Alliance for Patient Access. http://allianceforpatientaccess.org/press-release-statement-from-brian-kennedy-on-fridays-icer-meeting-in-boston. Posted March 21, 2017. Accessed April 20, 2017.
6. American College of Rheumatology. Rheumatology community responds to ICER Rheumatoid Arthritis Report. www.eurekalert.org/pub_releases/2017-04/acor-rcr040717.php. Posted April 7, 2017. Accessed April 20, 2017.
7. Arthritis Foundation. Arthritis Foundation proclaims a patient advocacy “win” through its work with the Institute for Clinical and Economic Review (ICER). www.arthritis.org/about-us/news-and-updates/arthritis-foundation-proclaims-a-patient-advocacy-win-through-its-work-with-icer.php. Released April 10, 2017. Accessed April 20, 2017.
8. CreakyJoints. CreakyJoints Protests ICER’s Rheumatoid Arthritis Evidence Report. www.ghlf.org/creakyjoints-protests-icers-rheumatoid-arthritis-evidence-report. Released March 24, 2017. Accessed April 20, 2017.