Évaluation comparative des critères de remboursement des antirhumatismaux modificateurs de la maladie parmi les régimes d’assurance-médicaments publics : analyse de l’environnement

Veuillez noter que la version intégrale de ce rapport est disponible en anglais seulement

Context

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease.^1,2 It is characterized by the infiltration of T cells, B cells, and monocytes into the synovial membranes of multiple joints — which is thought to play an important role in the pathophysiology of RA.^2,3 RA is a debilitating disease that affects physical functioning, work productivity, and health-related quality of life.³ If left untreated or insufficiently treated, 80% of patients will develop joint deformity and 40% will be unable to work within 10 years of disease onset.³ The cause of RA is not known and there is no cure. According to the Canadian Chronic Disease Surveillance System, RA affected 1.25% of the Canadian population aged 16 and older in 2016.⁴ Although RA affects persons of all ages, more than half of all new cases are diagnosed in persons between the ages of 40 and 70 years, and the prevalence of disease is approximately two times higher among women than among men.^4,5

Disease-modifying antirheumatic drugs (DMARDs) are a class of medications used to treat the signs and symptoms associated with RA, to slow the progression of disease, and to improve physical function.³ These include synthetic DMARDs and biologic DMARDs.³ Synthetic DMARDs are small molecules, whereas biologic DMARDs are large proteins that target specific components of the immune response and are administered parenterally. Biologic DMARDs are further classified into tumour necrosis factor (TNF) inhibitors and non-TNF inhibitors.^2,3 The majority of biologic DMARDs currently approved for use in Canada are TNF inhibitor drugs and include adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. Other available biologic DMARDs include the following non-TNF inhibitors: abatacept (T cell co-stimulatory inhibitor), anakinra (interleukin-1 receptor antagonist), rituximab (B lymphocyte-depleting drug), sarilumab, and tocilizumab (interleukin-6 receptor antagonists).^6,7 Several biosimilar drugs are also currently marketed in Canada, including etanercept, infliximab, and rituximab biosimilars; the biosimilar adalimumab has been approved by Health Canada but is not yet marketed.⁸ Health Canada approved the biologics to be used in combination with one or more conventional synthetic DMARDs (usually methotrexate); all biologics except infliximab, golimumab, and rituximab are approved for use as monotherapy.^6,7

In Canada, provincial and territorial (P/T) public drug plans generally provide prescription drug coverage for specific segments of the population such as seniors (persons aged older than 65 years), individuals with low income, or those with high drug costs relative to their income; public coverage is therefore determined based on predefined eligibility criteria for the general population. Additionally, federal public drug plans provide coverage for veterans, First Nations and Inuit individuals, federally incarcerated offenders, the Royal Canadian Mounted Police, and the military. Public drug plans list prescription medicines according to specific coverage categories that can be broadly classified as restricted benefits or unrestricted benefits. “Unrestricted benefit” refers to drugs whose usage is not limited by clinical criteria requiring authorization. Depending on the P/T drug plans, this type of formulary benefit status (coverage category) is referred to as open benefit, full benefit, or regular benefit. “Restricted benefit” refers to drugs whose usage is limited by specific clinical criteria or to a defined  patient subgroup. Depending on the jurisdictional plan, this type of formulary benefit status is categorized under Special Authorization, Exceptional Access Program (EAP), Exceptional Drug Status (EDS), Limited Use, Limited Coverage Drug, Prior Authorization. An active approval process is often assumed for drugs within the restricted benefit category; that is, there is a requirement to submit an application for reimbursement, with the required clinical details by the authorized prescriber using established processes (e.g., use of specific authorization forms). Submitted requests for restricted benefit drugs are often subject to a medication review by the P/T drug plan prior to approval for coverage.⁹

Advances in therapy for patients with RA in the last 20 years have led to better disease management strategies and improved patient outcomes.^3,10 The introduction of new therapies over time has resulted in increased public drug program spending on RA treatment.¹¹ In light of budget constraints, public health care payers have implemented criteria to restrict the use of pharmacotherapies for RA, including biologic DMARDs, to particular patient subgroups.¹²

An environmental scan (ES) was conducted to better understand the similarities and differences between the current public drug program access criteria for biologic drugs used to treat RA in Canada. This ES is intended to inform a CADTH multicomponent Technology Review that aims to address a broader policy question regarding the harmonization of public coverage policies for biologic drugs for patients with RA in Canada.¹³

Objectives

The objective of this ES was to identify and to compare existing criteria for reimbursing biologic drugs in RA across Canadian public formularies. This ES did not include an assessment of the comparative clinical effectiveness or the relative cost-effectiveness of biologic drugs used to treat RA. Therefore, any conclusions or recommendations about the value of these medications or their place in therapy were outside of the scope of this report.

Methods

The findings of this ES are based on information obtained from formulary databases (drug benefit lists) accessed through Canadian public drug plan formulary websites. No bibliographic literature searches were performed. Online formularies were searched between April 16, 2020 and April 30, 2020. Members of the CADTH Pharmaceutical Advisory Committee Formulary Working Group for Health Technology Assessments (FWG-HTA)¹⁴ — which includes representatives from the federal, provincial, and territorial health ministries,  and related health organizations — were consulted to validate the information gathered from the formulary databases and provide feedback on the report findings. The consultation period ended on July 9, 2020; therefore, the information summarized in this report is up-to-date as of July 9, 2020.

This report includes relevant formulary coverage policies regarding all publicly reimbursed biologics and biosimilar DMARDs used in the treatment of RA. Only policies relevant to biologic drugs used in the treatment of adult patients with RA were included. Hence, anakinra, an interleuken-1 inhibitor, was excluded from this report, as this drug is rarely used to treat RA in adults.¹⁵ Private payer policies were also excluded from this report given the focus on the Canadian publicly funded health care system. It should be noted that biologic DMARDs included in this ES are also indicated for other medical conditions; however, this report presents the coverage criteria specific to the RA indication. Some information presented in this report was not available in the public domain and was obtained through personal communication with members of the CADTH FWG-HTA. When this occurred, permission was obtained to publish this information in this report and all details obtained through personal communication were referenced accordingly.

Table 1 presents information on the components of the information presented in this ES: a list of the 14 drugs (nine originator biologics and five biosimilars) and the 14 publicly funded drug plans of interest (nine provincial, one territorial and four federal drug plans), and the type of information gathered. The term “drugs” is used throughout this report to refer to the originator biologics and their biosimilar variants (if available) used in the management of RA, as listed in Table 1; “originator biologics” are also commonly referred to as reference biologics or innovator biologics. Canadian provincial and territorial abbreviations were used to refer to the respective jurisdictional drug plan formularies. Information on four federal public drug plans was also included: Non-Insured Health Benefits (NIHB), Correctional Services Canada (CSC), Veterans Affairs Canada (VAC), and the Canadian Armed Forces (CAF). It should be noted that publicly reimbursed medications for residents of Nunavut and the Northwest Territories follow the coverage category and reimbursement criteria of the NIHB program.^16,17 The Quebec public drug program — Régie de l'assurance maladie du Québec — was not included in this report.

Synthesis Approach

A qualitative comparison using a systematic approach was adopted to identify the similarities and differences between the reimbursement criteria. Information regarding coverage criteria was presented for each drug according to specific requirements reported by individual drug plans and the relevant coverage categories. Other policies that may be relevant for reimbursing biologic DMARDs were also presented in this report, such as policies on the use of biosimilar drugs and biosimilar switching.

Table 1: Components for Information Gathering

DMARDs = disease-modifying antirheumatic drug; PEI = Prince Edward Island; RA = rheumatoid arthritis.

Research Questions

This following research question was addressed:

What are the similarities and differences between the reimbursement criteria issued by Canadian publicly funded drug plans for currently available biologic DMARDs used in the treatment of adult patients with RA?

Findings

A summary of findings relating to jurisdictional coverage policies for biologic DMARDs used in the treatment of patients with RA is presented in the sections that follow. Available information was presented to showcase the similarities and differences in the coverage status and the reimbursement criteria for drugs within and between public drug plans.

1. Jurisdictional drug coverage

Most jurisdictional drug plans provided coverage for almost all the drugs included in this report. Namely, nine out of 14 drug plans (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, New Brunswick, Newfoundland and Labrador, Prince Edward Island, NIHB) provided coverage for all originator biologic drugs. Two originator biologics were not publicly reimbursed by some jurisdictions:

• Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF.
• Sarilumab was not eligible for reimbursement by Nova Scotia, Yukon, and CSC.

All jurisdictions except VAC provided coverage for etanercept and infliximab biosimilars; coverage may be provided by VAC in exceptional cases while these drugs are under review and case-by-case assessment follows the originator biologic criteria for RA. (Anne Bastarache, Veterans Affairs Canada: personal communication, Jul 2020). It should be noted that while all jurisdictions provided coverage for all available etanercept and infliximab biosimilars, one infliximab biosimilar, Renflexis, was not eligible for reimbursement by Yukon. Conversely, three jurisdictions (Alberta, Ontario, and Yukon) provided coverage for Truxima, a rituximab biosimilar. Of note, Truxima was approved by Health Canada in December 2019 and the pan-Canadian Pharmaceutical Alliance negotiation process for Truxima concluded in February 2020. Hence, the coverage status of Truxima by the drug plans may change in the near future.^18,19

2. Coverage categories

All the drugs were listed under “restricted benefit” categories such as Special Authorization, EAP, EDS, Limited Coverage Drug, Limited Use, and Prior Authorization, with the following exceptions:^8,20-36

• The biosimilar versions of etanercept, infliximab, and rituximab were listed as a Limited Use benefit by Ontario.
• All drugs were listed as a “benefit with criteria medications” by CSC.

Of note, requests for the biosimilar versions of etanercept and infliximab for patients with RA covered by VAC are assessed on a case-by-case basis, as per the originator biologic criteria. (Anne Bastarache: personal communication, Jul 2020).

As a restricted benefit, all the drugs across all public drug plans were reimbursed under specific medical circumstances because these drugs are effective within certain patient subgroups or are more costly than other, equally safe and effective, drug treatments. In general, the plans required individuals to meet specific clinical criteria for drugs to be eligible for reimbursement. These clinical criteria are typically established by each plan’s formulary review committee. For biologic DMARDs (and their biosimilars) used to treat patients with RA, these criteria included a requirement for failure to respond to a first- or a second-line of therapy. Initial or continued coverage was provided for a specific period or indefinitely, depending on the drug and the jurisdictional drug plan.

The restricted benefit categories can be further classified by the following reimbursement processes: restricted benefit-active and restricted benefit-passive.

Restricted Benefit – Active was applicable to the following coverage categories for biologic DMARDs for RA: Special Authorization/Limited Coverage Drug (British Columbia), Special Authorization (Alberta, New Brunswick, Newfoundland and Labrador, Prince Edward Island, Veterans Affairs Canada, Canadian Armed Forces), EAP (Ontario), EDS (Saskatchewan, Manitoba, Nova Scotia, Yukon), or limited use/prior authorization (NIHB). Application for public reimbursement with the required clinical details must be made by the authorized prescriber using established processes (e.g., use of specific authorization forms). Each  request is subject to a medication review by staff responsible for claims adjudication at the public drug plan. ^8,20-36

Restricted Benefit – Passive was applicable to the following coverage categories for biologic DMARDs for RA: Limited Use (Ontario), and benefit with criteria medications (CSC). As opposed to “Restricted Benefit – Active,” the use of specific authorization forms and a medication review is not a requirement. Rather, a Limited Use code (Ontario) or a Reason for Use code (CSC) must be specified in the prescription. Of note, in Ontario, biosimilars are listed as Limited Use, while the originator biologics are listed as EAP. ^8,20-36

Table 2 presents information on the coverage category (grouped as restricted benefit-active and restricted benefit-passive) for each drug according to each public drug plan. Appendix 1 provides a detailed overview of the specific coverage category — that is, the formulary benefit status terminology used by jurisdictions — and Appendix 2 provides web links for detailed descriptions of each of the jurisdiction-specific coverage categories.

Table 2: Coverage Categories

AB = Alberta; BC = British Columbia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; MB = Manitoba; NAB = not a benefit; NB = New Brunswick; NIHB = Non-Insured Health Benefits;
NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PAS = restricted listing – passive (e.g., Limited Use benefit for Ontario); PE = Prince Edward Island; RES = restricted benefit with specified criteria (e.g., Special Authorization, exception drug status, Limited Use benefit for NIHB); SK = Saskatchewan; UR = under review; VAC = Veterans Affairs Canada; YT = Yukon.
^a Also applicable to Nunavut and the Northwest Territories.
^b Biosimilar version.
^c Overage may be provided in exceptional cases while the drug is under review and case-by-case assessment follows the originator biologic criteria for rheumatoid arthritis. Information is based on a personal communication with the jurisdictional representative (Anne Bastarache: personal communication, Jul 2020).
Source: Canadian public drug plan formularies ^8,20-36

3. Clinical Criteria

The following section summarizes the clinical requirements for patients with RA to be approved for coverage for a biologic DMARD. Biosimilar related policies which may impact access to originator biologics are also discussed. ^37-39

a) Diagnosis and prescriber requirements

The drugs were generally eligible for coverage for patients with moderate to severely active RA; some variation was noted in the diagnosis definitions used (Table 3). Ontario explicitly defined the disease activity.⁸ However, other drug plans such as British Columbia required that details of the disease activity be specified in the application forms.^25,26 Of note, Manitoba stated that the initial application information must include information on disease activity such as the number of tender and swollen joints, the erythrocyte sedimentation rate, and the C-reactive protein value for certolizumab pegol, etanercept, golimumab, infliximab, sarilumab, and tocilizumab.⁴⁰

Table 3: Details on Diagnosis

AB = Alberta; BC = British Columbia; CAF =Canadian Armed Forces; CCP = cyclic citrullinated peptide; CSC = Correctional Services Canada; MB = Manitoba; NB =New Brunswick; NIHB = Non-Insured Health Benefit; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; RA = rheumatoid arthritis; SK = Saskatchewan; VAC = Veterans Affairs Canada; YT = Yukon.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by YT. Sarilumab was not eligible for reimbursement by NS, YT and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, ON and YT. Coverage for etanercept and infliximab biosimilars may be provided in exceptional cases by VAC while the drugs are under review (Anne Bastarache: personal communication, Jul 2020).
Source: Canadian public drug plan formularies^8,20-36

As noted in Table 4, most of the public drug plans explicitly stated that the drug must be prescribed by a “rheumatologist” or a “prescriber with a specialty in rheumatology.” In addition to these prescribers, VAC also allowed an “internal medicine specialist” to prescribe these drugs.

Table 4: Prescriber Requirement

AB = Alberta; BC = British Columbia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; MB = Manitoba; NB = New Brunswick; NIHB = Non-Insured Health
Benefits; NL= Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; SK = Saskatchewan; VAC = Veterans Affairs Canada; YT = Yukon.
^a Or internal medicine specialist.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by YT. Sarilumab was not eligible for reimbursement by NS, YT, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, ON, and YT. Coverage for etanercept and infliximab biosimilars may be provided in exceptional cases by VAC while the drugs are under review (Anne Bastarache: personal communication, Jul 2020).
Source: Canadian public drug plan formularies ^8,20-36

b) Prior Therapy

None of the drugs were eligible for coverage as a first line of therapy. In general, patients seeking reimbursement for biologic DMARDs must have experienced failure on an initial treatment such as a conventional synthetic disease-modifying antirheumatic drug (csDMARD) — or in some cases, an anti-TNF agent — or to have experienced intolerance or serious adverse effects with initial therapy to be eligible for coverage.^8,20-36

Table 5 presents the details on the requirements for prior therapy for each drug or group of drugs. The drugs were only reimbursed if patients were “refractory,” “intolerant,” or failed to respond to previous therapy with csDMARDs. “Refractory” was defined as a lack of effect at the recommended doses and for a specified duration of treatment. “Intolerant” was defined as demonstrating serious adverse effects or contraindications to treatments, as defined in the product monographs. Previous therapy that included methotrexate alone or in combination with other DMARDs was applicable to all public drug plans, and for all drugs unless contraindicated or not tolerated. These clinical criteria varied between the drug plans, especially regarding the number and the sequence of csDMARDs (or csDMARD combination regimens) that needed to be tried before requesting reimbursement for the biologic DMARDs. Three out of 14 drug plans (Alberta, Manitoba, and Yukon) required failure to at least three lines of prior therapy, including at least one line of methotrexate monotherapy (unless contraindicated or not tolerated) and at least one subsequent line of combination therapy with csDMARDs, before being eligible for coverage with biologic DMARDs. Seven out of 14 drug plans (Saskatchewan New Brunswick, Nova Scotia, Prince Edward Island, CSC, VAC, and CAF) required failure to at least two lines of prior therapy, including one line of methotrexate monotherapy (unless contraindicated or not tolerated) and/or therapy with one or more csDMARDs before being eligible for coverage with biologic DMARDs. British Columbia, Ontario, Newfoundland and Labrador, and NIHB specified an option for access to biologic DMARDs after only one line of dual or triple therapy with csDMARDs. The duration of monotherapy or combination therapy with csDMARDs ranged from 8 weeks to 4 months. CSC and CAF required failure on at least one anti-TNF therapy, in addition to csDMARDs, to be eligible for coverage for tocilizumab. Yukon and NIHB required failure on at least one anti-TNF therapy, in addition to csDMARDs, to be eligible for coverage for abatacept. Prior therapy criteria for rituximab were the same across all drug plans; that is, a failure to respond to an adequate trial of at least one anti-TNF agent, in addition to jurisdictional requirements for prior therapy with csDMARDs.^8,20-36

Patients covered by Alberta were permitted to switch from one biologic DMARD to another following an adequate trial of the first biologic agent if patients were unresponsive to initial therapy, or due to serious adverse effects or contraindications. An adequate trial was defined as a minimum completion of induction dosing (e.g., initial coverage period). However, patients were not permitted to switch back to a previously trialled biologic drug if they were deemed unresponsive to that treatment.^8,20-36 CSC required evidence of failure or intolerance with a subcutaneous biologic (e.g., adalimumab) prior to initiating treatment with an IV biologic (e.g., infliximab, abatacept, tocilizumab).²²

Table 5: Requirement for Failure to Prior Line of Therapy

AB = Alberta; BC =British Columbia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; DMARDs = disease-modifying antirheumatic drugs;
HAQ = Health Assessment Questionnaire; HCQ = hydroxychloroquine; IM = intramuscular; LEF= leflunomide; MB = Manitoba; MTX = methotrexate; NB = New Brunswick;    NIHB = Non-Insured Health Benefit; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; p.o. = orally; SC= subcutaneous;
SK = Saskatchewan; SSZ = sulfasalazine; TNF= tumour necrosis factor; VAC = Veterans Affairs Canada; YT = Yukon.
^a “Refractory” is defined as lack of effect at the recommended doses and for the duration of treatments specified in the table. “Intolerant” is defined as demonstrating serious adverse effects or contraindications to treatments as defined in product monographs.
^b Patients who do not exhibit a clinical response or experience gastrointestinal intolerance to p.o. MTX may have a trial of parenteral MTX before being accepted as refractory.
^c Actemra (tocilizumab), Brenzys (etanercept), Cimzia (certolizumab pegol), Erelzi (etanercept), Inflectra (infliximab), Kevzara (sarilumab), Orencia (abatacept), Renflexis (infliximab), Simponi (golimumab), Xeljanz (tofacitinib).
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by Yukon. Sarilumab was not eligible for reimbursement by Nova Scotia, Yukon, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by Alberta, Ontario, and Yukon.
Coverage for etanercept and infliximab biosimilars may be provided in exceptional cases by VAC while the drugs are under review. (Anne Bastarache: personal communication, Jul 2020).
Source: Canadian public drug plan formularies ^8,20-36

c) Use of Concomitant Drugs

Seven out of 14 drug plans stated that concomitant treatment with methotrexate (MTX) or another csDMARD was mandatory for all drugs. Where MTX is contraindicated or not tolerated, Alberta, Saskatchewan, and Ontario permitted the use of specific biologic
DMARDs as monotherapy, including: adalimumab (Alberta, Saskatchewan), certolizumab pegol (Saskatchewan), etanercept (Saskatchewan), infliximab (Saskatchewan), golimumab (Saskatchewan), sarilumab (Alberta, Ontario) or tocilizumab (Alberta). Of note, (Alberta, Saskatchewan, New Brunswick, Nova Scotia, Newfoundland and Labrador, and Prince Edward Island explicitly stated that patients were limited to receiving one immunosuppressive biologic drug at a time, regardless of the condition for which it was being prescribed^8,20-36

Table 6 provides details on use of concomitant drugs. ^8,20-36

Table 6: Concomitant Drugs

AB = Alberta; BC = British Columbia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; csDMARDs = conventional synthetic disease-modifying antirheumatic drugs DMARDs = disease-modifying antirheumatic drugs; MB = Manitoba; MTX = methotrexate; NB = New Brunswick; NIHB = Non-Insured Health Benefit; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; SK =Saskatchewan; TNF= tumour necrosis factor; VAC = Veterans Affairs Canada; YT=Yukon.
^a To be combined with MTX.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by Yukon. Sarilumab was not eligible for reimbursement by Nova Scotia, Yukon, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by Alberta, Ontario, and Yukon. Coverage for etanercept and infliximab biosimilars may be provided in exceptional cases by VAC while the drugs are under review (Anne Bastarache: personal communication, Jul 2020)
Source: Canadian public drug plan formularies. ^8,20-36

d) Approved Dose, Duration, and Supply Limits

There were considerable differences across jurisdictions regarding the approved duration of initial therapy and requirements for treatment renewal for the drugs. Alberta had the shortest duration for the initial approval period for all drugs. A six-month or annual initial duration of approval and a renewal at every 12 months thereafter was most reported. However, Ontario allowed a one-year period for first renewal, with subsequent renewals at every five years for all drugs. British Columbia allowed indefinite renewal for most of the drugs. NIHB allowed indefinite approval for the biosimilar version of etanercept and infliximab. Although renewals of rituximab were not possible across drug plans, many drug plans allowed a second course of therapy for this drug. Table 7 provides details about the duration of initial approval and renewal periods. ^8,20-36

Nine out of 14 drug plans required confirmation of a clinical response to the drug for renewal of coverage; in most cases, this was a minimum improvement in the American College of Rheumatology (ACR) criteria — the ACR 20 response. Table 7 provides the specific details relating to renewal criteria for the drugs across all drug plans.^8,20-36

Dose limits were highly similar between drug plans. Ontario required a planned dosing regimen to be submitted with the request for coverage. Ontario, New Brunswick, Nova Scotia, Newfoundland and Labrador, and Prince Edward Island explicitly stated that dose escalation was not permitted for one or more drugs. Table 9 provides the specific details of the dose limits for the drugs across all drug plans. ^8,20-36

Information on supply limits for one or more drugs was available for British Columbia, Alberta, Saskatchewan, and the Yukon (Table 10).^20,25,26,32

Table 7: Approval Duration for Initial Therapy and Treatment Renewal

AB = Alberta; BC = British Columbia; CSC = Correctional Services Canada; MB = Manitoba; NB = New Brunswick; NIHB =Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; SK = Saskatchewan; VAC = Veterans Affairs Canada; YT = Yukon.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by YT. Sarilumab was not eligible for reimbursement by NS, YT, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, ON and YT.
Source: Canadian public drug plan formularies ^8,20-36

Table 8: Renewal Criteria

AB = Alberta; ACR = American College of Rheumatology; BC = British Columbia; CSC = Correctional Services Canada; DAS = disease activity score; HAQ = Health Assessment Questionnaire; NB = New Brunswick; NIHB = Non-Insured Health Benefits; NL =Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE=Prince Edward Island.
a The ACR 20 response is a 20% reduction in tender joint count and swollen joint count, and 20% improvement in at least three (3) of the following: patient's assessment of pain, patient's global assessment, physician's global assessment, patient's assessment of disability, and acute phase reactant measures — that is, erythrocyte sedimentation rate or C-reactive protein.
b The DAS28 score is reported to one decimal place. The HAQ score is reported to two decimal places. The initial score for the DAS28 or HAQ score will be rounded to the correct number of decimal places.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, VAC, or CAF. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by Yukon. Sarilumab was not eligible for reimbursement by Nova Scotia, Yukon, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by Alberta, Ontario, and Yukon.
Source: Canadian public drug plan formularies ^8,20-36

Table 9: Dose Limits

AB = Alberta; BC = British Columbia; CSC = Correctional Services Canada; IV = Intravenous; NB = New Brunswick; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; RA = rheumatoid arthritis; SC = subcutaneous.
Note: Certolizumab pegol was not eligible for reimbursement by CSC, Veterans Affairs Canada, or the Canadian Armed Forces. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by Yukon. Sarilumab was not eligible for reimbursement by NS, Yukon, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, ON, and Yukon.
Source: Canadian public drug plan formularies ^8,20-36

Table 10: Supply Limits

AB = Alberta; BC = British Columbia; SC = subcutaneous; YT = Yukon.
^a One infusion (dose) usually provides treatment for 56 days or less.
^b When dosed at 14-day intervals.
Note: Certolizumab pegol was not eligible for reimbursement by Correctional Services Canada (CSC), Veterans Affairs Canada, Canadian Armed Forces. Renflexis, an infliximab biosimilar, was not eligible for reimbursement by YT. Sarilumab was not eligible for reimbursement by Nova Scotia, YT, and CSC. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, Ontario, and YT.
Source: Canadian public drug plan formularies ^20,25,26,32

e) Biosimilar Policies

Of the 14 publicly reimbursed drugs for patients with RA, five were biosimilars; there were two etanercept biosimilars (Brenzys, Erelzi), two infliximab biosimilars (Inflectra, Renflexis), and one rituximab biosimilar (Truxima).^{8, 20-36} Etanercept and infliximab biosimilars were reimbursed by all drug plans except VAC, where coverage is currently determined on a case-by-case basis. Although the rituximab biosimilar was reimbursed by Ontario, Alberta, and Yukon,^{8, 20-36} its coverage status may changes in the future, as this drug was recently approved by Health Canada (in December 2019); the pan-Canadian Pharmaceutical Alliance negotiation process concluded in February 2020.^18,19

Findings regarding biosimilar policies revealed that, in most cases, jurisdictions provided coverage for biosimilars for biologic-naive patients only, and that patients who were stable on an originator biologic were permitted to continue their treatment, with an option to switch to a biosimilar. Conversely, biosimilar policies in British Columbia and Alberta mandate that all patients be administered biosimilar versions of etanercept and infliximab if they were treatment-naive, or switch to these biosimilars if they were already taking the originator biologics; the Alberta biosimilar policy will be effective as of January 15, 2021. Although no other drug plans had controlled switching policies that required existing originator biologic users to switch to a biosimilar, Newfoundland and Labrador and Manitoba specified that switching between originator biologics and biosimilar products was not permitted for infliximab and etanercept (Manitoba, only) if a patient was previously trialled on the originator drug or biosimilar and was deemed unresponsive to therapy. Table 11 provides details of biosimilars-related policies.

Manitoba, CSC, and VAC stated that the biosimilar version of etanercept and infliximab was the preferred option for all etanercept-naive and infliximab-naive patients, respectively.
However, Manitoba implemented a tiered biologics policy that is applicable to etanercept- and infliximab-naive patients and existing patients who have previously been trialled and deemed unresponsive to biologic therapy. According to this policy, biosimilars fall under Tier 1 and their corresponding originator biologic falls under Tier 2 drugs. Patients must fail to respond to more than two Tier 1 drugs to be eligible for coverage for Tier 2 drugs. ^{8, 20-36}

Table 11: Policies Related to Biosimilars

AB = Alberta; BC = British Columbia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; MB = Manitoba; NB = New Brunswick; NIHB = Non-Insured Health
Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; ON = Ontario; PE = Prince Edward Island; SK = Saskatchewan; VAC = Veterans Affairs Canada; YT = Yukon.
^a Originator biologics covered for patients who are medically unable to switch products. A new Special Authorization request for exceptional coverage is required, which will be reviewed by Special Authority on a case-by-case basis. This request had to be submitted before November 26, 2019 to ensure continued coverage.
^b Patients who are taking an originator biologic must switch to its biosimilar version by January 15, 2021. Only the biosimilar versions of the drugs will be covered after January 15, 2021.
^c Remicade (infliximab originator biologics) can be approved for infliximab-naive patients
Note: Renflexis, an infliximab biosimilar, was not eligible for reimbursement by YT. Truxima, a rituximab biosimilar, was only eligible for reimbursement by AB, ON, and YT. Coverage for etanercept and infliximab biosimilars may be provided in exceptional cases by VAC while the drugs are under review. (Anne Bastarache: personal communication, Jul 2020)
Source: Canadian public drug plan formularies ^8,20-36

Limitations

Formulary policies presented in this report are current up to the date of the final search of drug plans’ formulary databases and validation by the FWG-HTA members (July 9, 2020). These policies may change in the future, especially regarding the use of biosimilars as more biosimilar version of the originator biologic DMARDs enter the market. These findings are relevant to the Canadian federal (excluding the Royal Canadian Mounted Police health benefits program and the Immigration, Refugees and Citizenship Canada Federal Health Program), provincial (excluding Quebec), and territorial public drug plans, and did not include information about private payers or any international jurisdictions.

There were some gaps in information, as elements of coverage criteria were not available for one or more drugs. These included missing information on: initial and renewal periods (VAC, CAF, CSC, and NIHB), renewal criteria (Saskatchewan, Manitoba, VAC, CAF, and NIHB), or dose limits (Saskatchewan, Manitoba, VAC, CAF, CSC, and Yukon). Information on supply limits for one or more drugs was available for British Columbia, Alberta and Yukon, but not specified for other plans.

Conclusions and Implications for Decision- or Policy-Making

This ES sought to identify and to compare criteria for reimbursing 14 biologic DMARDs used to treat patients with RA across 14 federal, provincial, and territorial public drug programs in Canada. The information in this report was collected from the public domain — namely, the online formulary databases or drug benefit lists — and subsequently validated by drug plan representatives who were members of the CADTH FWG-HTA Committee.

Most jurisdictional drug plans provided coverage for almost all the drugs included in this report; exceptions included certolizumab pegol; sarilumab; and biosimilar versions of infliximab, etanercept, and rituximab, which were not reimbursed by one or more drug plans. Of note, infliximab biosimilars and etanercept biosimilars are under review by VAC, and Truxima, a rituximab biosimilar, is under review by British Columbia and Saskatchewan; therefore, these biosimilars may be reimbursed in the future by these drug plans. Biologic DMARDs and their biosimilars were listed as “restricted benefit” for RA (for example, as Special Authority, EAP, EDS, Limited Use, Limited Coverage Drug, or Prior Authorization benefit listing); that is, drugs that are reimbursed according to specific criteria and often requiring the use of specific authorization forms. Twelve out of 14 drug plans required an “active” approval process to access originator biologics and their biosimilar versions; that is, there is a requirement to submit an application for reimbursement and each request is subject to a medication review at the public drug plan prior to approval for coverage. The use of specific authorization forms and a medication review was not a requirement for drugs covered by CSC or for biosimilars in Ontario; instead, the reimbursement of these drugs follows as “passive” approval process through the use of Limited Use (by Ontario) or Reason for Use (by CSC) codes specified by prescribers in the prescription.

In general, biologic DMARDs were restricted to patients with moderate to severely active RA and had to be prescribed by a rheumatologist. Nine out of 14 drug plans (British Columbia, Alberta, Manitoba, Nova Scotia, New Brunswick, Newfoundland and Labrador, Prince Edward Island, and VAC) had similar prior therapy requirements for all of the drugs except for rituximab, while six plans (Saskatchewan, Ontario, Yukon, NIHB, CSC, and CAF) had discrete prior therapy requirements for abatacept, sarilumab or tocilizumab, in addition to rituximab.

The major difference between the drug plans was in the number of lines of prior therapy with csDMARDs that is required to be completed prior to being able to access a biologic DMARD. For most drugs, all drug plans required failure to respond to at least two or three lines of monotherapy or combination therapy with csDMARDs before being eligible for coverage with biologic DMARDs; except for British Columbia, Ontario, Newfoundland and Labrador, and NIHB, which provided an option to access biologic DMARDs after one line of combination therapy (dual or triple therapy) with csDMARDs. Some drug plans required failure to respond to at least one anti-TNF therapy, in addition to csDMARDs, to be eligible for coverage for tocilizumab (CSC and CAF) and abatacept (YT and NIHB). Prior therapy criteria for rituximab were the same across all drug plans; that is, a failure to respond to an adequate trial of at least one anti-TNF agent, which meant that patients also needed to fulfill the prior therapy requirement for csDMARDs according to the respective drug plans. As such, rituximab, abatacept, tocilizumab, and sarilumab required failure to the greatest number of prior lines of therapy before treatment with a biologic DMARD at one or more drug plans. Since the number of lines of prior therapy that RA patients are required to fail prior to accessing a biologic DMARD may affect the length of time it takes for a patient to ultimately access a biologic DMARD, the high degree of variability among jurisdictions with respect to this parameter represents a potential area for rationalizing access criteria across jurisdictions to better reflect an optimal approach to RA pharmacotherapy.

In addition to variability in the requirements for prior treatments, there was variation among the drug plans regarding several other access criteria. Half of the drug plans included in    this scan mandated concomitant treatment with methotrexate or another csDMARD for all biologic DMARDs and their biosimilars. Many drug plans did not allow concomitant use with other biologic DMARDs, especially for rituximab. There were considerable differences regarding the approved duration of initial therapy and the timing of treatment renewal for the drugs between the drug plans. Eight out of 14 drug plans required confirmation of clinical response to the drug for renewal of coverage; in most cases, this was a minimum improvement of an ACR20 response. Dose limits for each drug were generally similar between all drug plans. Other than British Columbia and Alberta, no other drug plans had switching policies that required existing users of originator biologics to switch to a biosimilar. In most jurisdictions, biologic-naive patients were approved for coverage of biosimilar versions only, and patients stable on an originator biologic drug were permitted to continue their treatment, with option to switch to a biosimilar version.

In summary, the results of this ES have revealed that access criteria for biologic DMARDs   for RA are broadly similar in terms of being restricted for use in patients with moderate to severe RA, and after failing other, less costly treatments, such as csDMARDs. However, there is considerable heterogeneity in other criteria related to biologic DMARD reimbursement, including requirements for the number of prior treatments; concomitant use of other
treatments; and the duration of approval. Better alignment of criteria for biologic DMARDs for RA among public drug plans could promote the optimal use of public health care resources and equity in care.

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About this Document

Authors: Sirjana Pant, Mirhad Loncar

Acknowledgements: Kim Baird, Tarry Ahuja, Trevor Richter, Christine Perras

Cite As: Comparative Assessment of Coverage Criteria for Biologic Disease-Modifying Antirheumatic Drugs Across Canadian Public Drug Plans: An Environmental Scan.

Ottawa: CADTH; 2020 August. (Environmental scan; no. 94).

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