Drugs, Health Technologies, Health Systems
Indication: For the topical treatment of mild to moderate atopic dermatitis in patients 6 years of age and older
Sponsor: Arcutis Canada, Inc.
Final recommendation: Do not reimburse
Summary
What Is the Reimbursement Recommendation for Zoryve?
Canada’s Drug Agency (CDA-AMC) recommends that Zoryve not be reimbursed by public drug plans for the topical treatment of mild to moderate atopic dermatitis (AD) in patients aged 6 years and older with inadequate response, intolerance, or contraindications to topical corticosteroids (TCSs).
Why Did CDA-AMC Not Recommend Reimbursement?
Evidence from 2 clinical trials showed that after 4 weeks of treatment, Zoryve reduced AD severity and itching compared with the vehicle cream in patients aged 6 years or older with mild to moderate AD and inadequate response, intolerance, or contraindications to TCSs. However, there was little to no difference between Zoryve and the vehicle cream in improving health-related quality of life (HRQoL).
The clinical trials compared Zoryve with only the vehicle cream and did not include any active comparators. The sponsor submitted a network meta-analysis (NMA) to provide an indirect comparison of Zoryve with crisaborole, ruxolitinib, tacrolimus, and low- to medium-potency TCSs; however, the evidence was insufficient to draw definitive conclusions. This was due to several sources of uncertainty, including the heterogeneity across included trials, the lack of a closed loop involving Zoryve, uncertainty about whether the included studies could be compared fairly, and inconclusive data for several outcomes due to sparse networks.
The Canadian Drug Expert Committee (CDEC) acknowledged that mild to moderate AD in patients with inadequate response, intolerance, or contraindications to TCSs is a condition with substantial disease burden and that patients identified a need for treatments that can improve disease severity or symptom control (e.g., itching, dryness, flaking, inflammation, blistering, and cracked skin), reduce flares, and improve quality of life (e.g., better sleep, less discomfort or pain, improved productivity, and activities of daily living). However, CDEC noted that the available evidence did not clearly demonstrate that Zoryve addresses these unmet needs as effectively as, or more effectively than, other available treatment options. In addition, evidence on the long-term effects of Zoryve is limited.
Disease background: AD is a chronic, multifactorial, incurable inflammatory skin disease that is common in adults and children. AD is characterized by severe itching and recurrent eczematous lesions, which have a substantial physical and psychosocial impact on patients and their families. The estimated prevalence of AD in Canada is approximately 4% among adults and 15% among children, with most experiencing mild to moderate AD.
Indication and reimbursement request: Roflumilast 0.15% weight-by-weight percentage (w/w) cream (Zoryve) has been approved by Health Canada for the topical treatment of mild to moderate AD in patients aged 6 years and older. The sponsor is seeking reimbursement for the topical treatment of mild to moderate AD in patients aged 6 years and older with inadequate response, intolerance, or contraindications to TCSs.
Drug under review: Roflumilast is a PDE4 inhibitor that inhibits PDE4 and subsequent inflammatory markers associated with plaque psoriasis, AD, or seborrheic dermatitis. It is available as a 0.15% w/w topical cream recommended by the product monograph to be applied once daily to affected areas of skin and rubbed in completely.
Treatment costs: At the submitted price of $290.00 per 60 g tube, the annual cost of roflumilast 0.15% w/w cream is expected to be $355 per patient based on the Health Canada–recommended dosage and assuming an average of 18 administration-days per year, application on 13.6% of body surface area at 0.3g per 1% area, and no wastage.
The Eczema Society of Canada (a patient group) noted the following impacts of the disease, unmet needs, and important outcomes:
AD negatively affects HRQoL by causing persistent itchiness, poor sleep, anxiety, and unpredictable flares. It can also pose challenges with intimacy and personal relationships, and negatively impact mood, work, school, and social interactions.
AD also places a burden on caregivers and families, including financial strain and emotional challenges such as helplessness, guilt, and frustration.
Some patients find the currently available topical treatments to be inadequate and are frustrated by the trial-and-error approach of cycling through treatments. Moreover, treating certain areas of the body, such as the face, eyelids, neck, genitals, and joint areas, is particularly challenging due to constant use, friction, and exposure.
Important treatment goals for patients with AD included improvements in disease control, reduced incidence of flares and symptoms, improved sleep, and relief from daily pain, discomfort, and psychological distress.
Three clinician groups (the Canadian Dermatology Association, the Dermatology Association of Ontario, and the Atlantic Dermatology Group), as well as the clinical experts consulted by CDA-AMC, noted the following regarding unmet needs related to AD and place in therapy for roflumilast 0.15% w/w topical cream:
Available treatment options for AD are often associated with limited efficacy and tolerability, especially for patients with facial or intertriginous involvement.
Several barriers hinder treatment success in AD, including concerns about steroid-related side effects, poor adherence to twice-daily regimens, limited availability of effective nonsteroid treatments (e.g., crisaborole), and restrictions on newer drugs (e.g., ruxolitinib) due to safety warnings and body surface area limitations.
Roflumilast 0.15% w/w cream would be best suited as a first-line topical treatment for mild to moderate AD, or as a second-line option when TCSs are ineffective or unsuitable.
The participating public drug programs raised potential implementation issues related to initiating and prescribing roflumilast 0.15% w/w topical cream if CDEC recommended its reimbursement.
With a vote of 14 to 0, CDEC recommends that roflumilast 0.15% w/w cream not be reimbursed for the topical treatment of mild to moderate AD in patients aged 6 years and older with inadequate response, intolerance, or contraindications to TCSs.
During the initial and reconsideration meetings, CDEC concluded that, based on the totality of the clinical evidence, it is uncertain whether roflumilast 0.15% w/w cream demonstrates acceptable clinical value compared with topical calcineurin inhibitors (TCIs), which are also indicated for patients aged 6 years and older with inadequate response, intolerance, or contraindications to TCSs. Given that roflumilast 0.15% w/w topical cream is expected to be an alternative to TCSs, acceptable clinical value refers to at least comparable value versus TCIs.
CDEC noted that the INTEGUMENT-1 and INTEGUMENT-2 trials compared roflumilast 0.15% w/w cream to the vehicle cream alone without any active comparators. Evidence from 2 RCTs demonstrated that treatment with roflumilast 0.15% w/w topical cream for 4 weeks resulted in reductions in disease severity and worst itch intensity in the treatment of mild to moderate AD in patients aged 6 years and older with inadequate response, intolerance, or contraindications to TCSs compared with the vehicle cream alone. Within the study population, 57% to 66% of participants had either intolerance or contraindications to TCS therapy, or the condition exhibited inadequate response to adequate TCS therapy. Subgroup analyses indicated that outcomes in this cohort of patients were generally consistent with those observed in the overall study population; however, these results are uncertain as they were not formally adjusted for multiplicity. Furthermore, the 95% confidence intervals (CIs) for the point estimate were relatively wider than those of the overall population, indicating greater uncertainty in the treatment effect estimates. CDEC noted that, with moderate certainty, the evidence suggests little to no difference in HRQoL outcomes between roflumilast 0.15% w/w cream and the vehicle cream.
An NMA comparing roflumilast 0.15% w/w topical cream with crisaborole, ruxolitinib, tacrolimus, and low- to medium-potency TCSs provided insufficient evidence to draw definitive conclusions about its comparative effectiveness due to uncertainty. This uncertainty stemmed from key limitations, including the absence of a closed loop involving roflumilast 0.15% w/w cream in any network, uncertainty in the assumption that the included studies could be fairly compared (i.e., challenges to the transitivity assumption), and limited data for several outcomes due to sparse networks.
Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.
During the initial and reconsideration meetings, CDEC acknowledged that mild to moderate AD can be associated with a substantial disease burden and impacts on quality of life, particularly for patients who are intolerant to or have contraindications to TCSs, or whose disease has not responded adequately to appropriate TCS therapy. However, CDEC could not determine that mild to moderate AD was a life-threatening or seriously debilitating condition across the entire patient population. CDEC also found no major barriers to evidence generation related to either the rarity of the condition or ethical concerns; therefore, it did not establish that there is significant unmet clinical need arising from the prevalence of the condition and/or the ethical framework for its clinical research. CDEC found no evidence suggesting that roflumilast 0.15% w/w cream could substantially reduce morbidity associated with AD.
Further information on the committee’s discussion around unmet clinical need is provided in the Summary of Deliberation section.
During the initial and reconsideration meetings, although CDEC did not identify a significant unmet nonclinical need, the committee noted the disproportionate impact of AD among certain populations. However, CDEC was unable to determine from the evidence whether roflumilast 0.15% w/w cream could better address any health inequity arising from AD compared to the currently available treatments.
Further information on the committee’s discussion around unmet nonclinical need is provided in the distinct social and ethical considerations domain in the Summary of Deliberation section.
During the initial and reconsideration meetings, CDEC could not recommend whether to reimburse roflumilast 0.15% w/w cream or not based on clinical value alone due to the uncertainty in clinical value; therefore, it also considered whether roflumilast 0.15% w/w cream addresses a significant unmet clinical need with an acceptable level of certainty in clinical value. CDEC could not recommend reimbursement even after taking this into account. Finally, it considered whether roflumilast 0.15% w/w cream addresses a significant unmet nonclinical need or health inequity and was unable to conclude that roflumilast 0.15% w/w cream addresses a significant unmet nonclinical need or health inequity to a degree that overcomes the uncertainty in clinical value and potential risks. Taking all the previously noted considerations into account, CDEC recommended that roflumilast 0.15% w/w cream not be reimbursed.
Because CDEC recommended that roflumilast 0.15% w/w cream not be reimbursed, further deliberation was not required on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations, or to ensure clinical value is realized.
CDEC considered all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, refer to Expert Committee Deliberation at Canada’s Drug Agency.
The committee considered the following key discussion points, organized by the 5 domains of value: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems.
The sponsor requested a reconsideration of the initial draft recommendation not to reimburse roflumilast 0.15% w/w cream for mild to moderate AD. There were 4 issues outlined by the sponsor in the request for reconsideration, including 1 related to low economic risk. CDEC discussed 3 of the issues but did not consider low economic risk because that was not discussed in the initial recommendation not to reimburse roflumilast 0.15% w/w cream for mild to moderate AD.
Appropriate comparators: During the initial meeting, CDEC noted that the INTEGUMENT-1 and INTEGUMENT-2 trials did not compare roflumilast 0.15% w/w cream to TCIs, which are also used in Canada for patients with mild to moderate AD with inadequate response, intolerance, or contraindications to TCSs.
Concerns about place in therapy: During the reconsideration meeting, the committee observed that while some clinicians indicated that they prescribe roflumilast 0.15% w/w cream as a second-line therapy following inadequate response to a TCS, others favoured its use as a first-line option. CDEC noted that although 56.9% to 65.8% of patients enrolled in the pivotal trials had prior TCS exposure, the inclusion criteria of the trials did not require prior treatment failure with a TCS, and it was unclear whether TCSs were unsuccessful after an adequate trial period. Therefore, CDEC determined that the evidence provided by the sponsor did not clearly define the place in therapy for roflumilast 0.15% w/w cream.
Efficacy versus the vehicle cream: During the initial meeting, CDEC noted that evidence from the phase III INTEGUMENT-1 trial (N = 654) and INTEGUMENT-2 trial (N = 683) demonstrated that, compared with the vehicle cream, treatment with roflumilast 0.15% w/w cream for 4 weeks resulted in greater improvements in disease severity, as evidenced by the proportion of patients who achieved a score of clear or almost clear on the Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) and a 75% reduction in Eczema Area and Severity Index (EASI-75) rate. In the INTEGUMENT-1 trial, the percentage difference [PD] was 17.4% (95% CI, 11.09 to 23.75) in favour of roflumilast 0.15% w/w cream. In the INTEGUMENT-2 trial, PD was 16.5% (95% CI, 10.61 to 22.42) in favour of roflumilast 0.15% w/w cream. Similarly, the proportion of patients achieving EASI-75 was higher with roflumilast 0.15% w/w cream than with the vehicle cream alone in the INTEGUMENT-1 trial (PD = 22.0%; 95% CI, 15.09 to 28.94) and the INTEGUMENT-2 trial (PD = 20.8%; 95% CI, 14.14 to 27.50). The results from the subgroup analyses in patients with inadequate response, intolerance, or TCS contraindications in the INTEGUMENT-1 and INTEGUMENT-2 trials were consistent with the findings for the overall study population, although the analyses were unadjusted for multiplicity.
For reduction in worst itch severity, PD in the WI-NRS success scale was 13.3% (95% CI, 4.01 to 22.60) in the INTEGUMENT-1 trial and 15.0% (95% CI, 6.52 to 23.54) in the INTEGUMENT-2 trial in favour of roflumilast 0.15% w/w cream. For improvements in general AD symptoms, the least squares (LS) mean change in Patient Oriented Eczema Measure score from baseline to 4 weeks was ████ ██████ ████ ███ █████ ██ ██████ in the INTEGUMENT-1 trial and ████ ██████ ████ ███ █████ ██ ██████ in the INTEGUMENT-2 trial. For HRQoL in adults, the LS mean change in the Dermatology Life Quality Index (DLQI) from baseline to 4 weeks was −0.5 points (95% CI, −1.34 to 0.30) in the INTEGUMENT-1 trial and −1.6 points (95% CI, −2.51 to −0.59) in the INTEGUMENT-2 trial. In children, the LS mean change in the Children's Dermatology Life Quality Index (CDLQI) from baseline to 4 weeks was −2.1 points (95% CI, −3.04 to 1.22) in the INTEGUMENT-1 trial and −1.6 points (95% CI, −2.50 to −0.65]) in the INTEGUMENT-2 trial. However, conclusions for the DLQI and CDLQI outcomes are limited by a lack of adjustment for multiplicity, inadequate description of methods for handling missing data, and a high rate of missing DLQI data in treatment both arms.
Longer-term efficacy: During the initial meeting, CDEC note that the results of the single-arm, open-label extension phase of the INTEGUMENT trials suggest that treatment with roflumilast 0.15% w/w cream is safe for up to 52 weeks following the initial 4-week trial. The results from the INTEGUMENT open-label extension trial also suggested that treatment with roflumilast 0.15% w/w cream was associated with improvements in DLQI and CDLQI scores at week 52 from baseline. However, there was uncertainty with these outcomes due to a large amount of missing data.
Clinical importance of treatment effects: During the initial meeting, CDEC noted that, according to the patient group input, important outcomes include improving disease severity or symptom control (e.g., itchiness, dryness, flaking, inflammation, blistering, and cracked skin), reducing flares, and improving patients’ HRQoL (e.g., better sleep, less discomfort and/or pain, and improved productivity and ability to participate in activities of daily living). CDEC observed that treatment with roflumilast 0.15% w/w cream resulted in improvements in both measures of disease severity (vIGA-AD success and EASI-75) and exceeded the minimal important difference, indicating a clinically meaningful benefit compared to the vehicle cream. Similarly, the PD for the WI-NRS success score exceeded the minimal important difference, indicating a clinically meaningful benefit in reducing intense itching with roflumilast 0.15% w/w cream compared to the vehicle cream. However, the HRQoL outcomes did not show a clinically meaningful benefit with roflumilast 0.15% w/w cream compared to the vehicle cream.
Certainty of the evidence: During the initial meeting, CDEC noted that a Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment rated the certainty of evidence as high for the proportion of patients achieving vIGA-AD success and EASI-75 at week 4, whereas the certainty of evidence for WI-NRS at week 4 was rated as moderate. For quality of life outcomes, the certainty of evidence was rated as high for the CDLQI and moderate for the DLQI due to high dropout rates in both study arms and insufficient detail on the methods used for imputing missing data. The certainty of evidence for Patient Oriented Eczema Measure score was rated low due to imprecision in the estimates, wide 95% CIs, and inconsistent conclusions between the INTEGUMENT-1 and INTEGUMENT-2 trials.
Efficacy versus existing active treatments: During the initial meeting, CDEC note that the sponsor submitted 1 NMA indirectly assessing the relative efficacy and safety of roflumilast 0.15% w/w cream versus tacrolimus ointment, pimecrolimus, a low- or medium-potency TCS, a high-potency TCS, ruxolitinib cream, and crisaborole ointment for mild to moderate AD. The outcomes evaluated in the NMA were stringent treatment success, EASI-75 rate, DLQI and CDLQI scores at week 4, and all-cause discontinuation rate. Stringent success was defined as treatment success with an additional 2 or more points improvement in the vIGA-AD. Key limitations of the NMA included roflumilast 0.15% w/w cream not being a part of the closed loops in any of the networks; heterogeneities in baseline clinical and demographic characteristics of the study populations and trial characteristics, which undermined the transitivity assumption; and sparse networks for several comparisons, leading to imprecision and reduced certainty in effect estimates for some of the outcomes. Furthermore, the assessments were limited and did not include results beyond 4 weeks of treatment, and the long-term efficacy and safety of roflumilast 0.15% w/w cream compared to other treatments for mild to moderate AD were not evaluated. Due to its limitations, during the initial meeting, a definitive conclusion could not be drawn from the NMA regarding the comparative benefit of 1 drug over the other regarding improving disease severity (assessed as stringent success), EASI-75 rate, or HRQoL (measured using DLQI and CDLQI scores). Moreover, the NMA evidence was insufficient to conclude whether roflumilast 0.15% w/w cream differs from the other comparators in terms of all-cause discontinuation or withdrawal due to adverse events.
Impact of uncertainty: During the reconsideration meeting, CDEC discussed the sponsor’s claim that the initial recommendation not to reimburse roflumilast 0.15% w/w cream was partly due to overstating the impact of uncertainty in the comparative evidence versus TCIs. CDEC noted that the pivotal trials only compared roflumilast 0.15% w/w cream with the vehicle cream and did not include a direct comparison with any of the drugs currently used for the indication under review. Furthermore, the sponsor’s NMA included studies with differences in concomitant medications, vehicle compositions, and treatment formulations (all of which could influence treatment effects), as well as heterogeneity across trials in patient characteristics (e.g., age, prior treatment) and trial characteristics (e.g., treatment duration, outcome definitions). CDEC further noted the sponsor’s acknowledgement that the TCI trials included in the NMA were conducted using outdated standards and different outcome measures.
Higher standard of evidence: During the reconsideration meeting, CDEC considered the sponsor’s claim that the initial draft recommendation was based on an unrealistically high evidentiary threshold for AD topicals by concluding that the NMAs provided insufficient evidence to draw definitive conclusions on comparative effectiveness due to uncertainty and the absence of multiplicity adjustment for the inadequate response, intolerance, or contraindications TCS subgroup. CDEC emphasized that the initial draft recommendation was based on multiple deliberative considerations and the totality of the evidence reviewed, including the lack of strong comparative evidence between roflumilast 0.15% w/w cream and appropriate second-line therapies (e.g., tacrolimus), to adequately determine its relative efficacy and safety.
Clinical value: Based on all the preceding considerations, during the initial meeting, CDEC could not determine whether there was at least comparable clinical value versus TCIs, which are also used in Canada for patients with mild to moderate AD with inadequate response, intolerance, or contraindications to TCSs.
Input on unmet clinical need: During the initial meeting, CDEC note that patients identified a need for treatments that can improve disease severity or symptom control (e.g., itchiness, dryness, flaking, inflammation, blistering, and cracked skin), reduce flares, and improve quality of life (e.g., better sleep, less discomfort or pain, improved productivity, and activities of daily living). The clinical experts consulted by CDA-AMC indicated that when AD that affects the face, neck, intertriginous, or other sensitive areas does not respond adequately to a TCS, or if the patient is either intolerant of or contraindicated to TCS, they would avoid prescribing TCIs due to their potential for causing severe burning and stinging. CDEC noted that while roflumilast 0.15% w/w cream may be an alternative to TCIs in such cases, no clinical evidence was presented demonstrating it has a similar or better clinical value compared to TCIs.
Severity of the disease: During the initial meeting, CDEC acknowledged that AD can contribute to considerable discomfort and impaired quality of life because of itching, poor sleep, impact on relationships, anxiety, and unpredictable patterns. However, CDEC determined that mild to moderate AD is not a life-threatening or seriously debilitating disease or condition.
Availability of treatment options: During the initial meeting, CDEC note that effective and safe topical treatments are approved for mild to moderate AD in Canada, including first-line management, such as avoiding triggers, using moisturizers, and applying a low- to moderate-potency TCS (e.g., betamethasone, hydrocortisone, triamcinolone), as are second-line options such TCIs (e.g., pimecrolimus and tacrolimus). However, the clinical experts consulted by CDA-AMC also noted safety concerns with existing treatment options for mild to moderate AD, including skin atrophy, infections, other skin conditions that may occur with TCSs, intolerable burning and/or stinging with TCIs and crisaborole, and a boxed warning for serious infections, major adverse cardiovascular events, and thrombosis with ruxolitinib.
Significant unmet clinical need: During the initial meeting, CDEC note that although it acknowledged the need for treatments that improve disease severity, reduce flares, improve quality of life, and avoid the safety concerns of some existing treatments, the committee determined there was no significant unmet need as described in the recommendation framework in the Procedures for Reimbursement Reviews. During the initial and reconsideration meeting, CDEC could not determine that mild to moderate AD was a life-threatening or seriously debilitating condition across the entire patient population. Also, the committee did not identify a challenge with evidence generation due to either the rarity of the condition or ethical concerns.
Disease burden and limited therapy options: During the reconsideration meeting, CDEC discussed the sponsor’s claim that the initial recommendation did not reflect the substantial disease burden, important unmet clinical needs, and limitations of currently reimbursed therapies, despite evidence provided by patients and clinicians. CDEC recalled that the previous recommendation considered unmet clinical and nonclinical needs identified by patients and clinicians. The committee acknowledged the sponsor’s reference to data on the psychological impacts of AD (e.g., risk of suicide and stigma) and the effects of mild to moderate AD on sleep, school performance, and mental health. CDEC reiterated its agreement that mild to moderate AD in patients with inadequate response, intolerance, or contraindications to TCSs is a condition with substantial disease burden and unmet clinical needs. However, CDEC noted that the sponsor did not provide any conclusive evidence showing that roflumilast 0.15% w/w cream addresses these unmet needs as effectively as, or more effectively than, other currently available treatment options. In addition, evidence on the long-term effects of roflumilast 0.15% w/w cream remains limited.
Input on unmet nonclinical need: During the initial meeting, CDEC considered input from both patients and clinicians regarding their preference for a once-daily application regimen over a twice-daily regimen. Both groups noted that a once-daily formulation like roflumilast 0.15% w/w cream would be more convenient. In addition, the clinician group input stated that the once-daily application would improve treatment adherence. The committee also noted that once-daily formulations were mentioned by expert panels and in connection to adherence studies in other conditions requiring topical therapy, such as for psoriasis and acne. However, CDEC noted that the evidence presented did not address treatment adherence. CDEC also noted that evaluating convenience would be challenging given the absence of a defined metric to determine when convenience has been adequately met. Additionally, both patients and clinicians indicated that efficacy, safety, and HRQoL remain critical unmet needs in the management of mild to moderate AD.
Equity considerations: During the initial meeting, CDEC acknowledged the clinical experts’ input that AD disproportionately affects Indigenous populations with suboptimal access to moisturizers and clean water, and is also more common among Black people, children, and South Asian populations. However, CDEC was unable to determine how roflumilast 0.15% w/w cream could address any health equity concerns in AD better than other treatments options.
Significant unmet nonclinical need or health inequity: During the initial meeting, CDEC considered the disproportionate impact of AD among certain populations but was unable to determine from the evidence whether roflumilast 0.15% w/w cream could better address any health inequity arising from AD compared to available treatments.
Deliberation on economic considerations: During the initial meeting, the committee reviewed the economic considerations for roflumilast 0.15% w/w cream; however, the recommendation not to reimburse meant that further deliberation on economic considerations was not required.
Deliberation on impacts on health systems: The committee considered the impacts on health systems when implementing roflumilast 0.15% w/w cream; however, the recommendation not to reimburse meant that further deliberation on measures to address these impacts was not required.
During its initial meeting, CDEC considered the following information when making its recommendation (links to the full documents for the review can be found on the project webpage):
the CDA-AMC review of the clinical and pharmacoeconomic evidence submitted by the sponsor, as well as relevant ethical issues related to roflumilast 0.15% w/w cream (refer the Main Report and Supplemental Material document)
the sponsor’s comments on the draft report and the CDA-AMC responses
patients' perspectives gathered by 1 patient group, the Eczema Society of Canada
input from 3 clinician groups: the Canadian Dermatology Association, the Dermatology Association of Ontario, and the Atlantic Dermatology Group
input from the public drug programs that participate in the reimbursement review process (refer to the Supplemental Material document)
input from 2 clinical experts with expertise in the management of AD who were consulted by CDA-AMC.
The sponsor filed a request for reconsideration of the draft recommendation for roflumilast for mild to moderate AD. In their request, the sponsor identified the following issues:
CDEC inappropriately recommended that roflumilast 0.15% w/w cream not be reimbursed because it overstated the impact of uncertainty in the comparative data versus TCIs.
CDEC inappropriately set an unrealistically high standard of evidence for AD topicals by concluding the NMA provided insufficient evidence to draw definitive conclusions about its comparative effectiveness due to uncertainty and lack of multiplicity adjustment for the inadequate response, intolerance, or contraindications to TCS subgroup.
CDEC did not consider mild to moderate AD in patients with inadequate response, intolerance, or contraindications to TCSs to represent an important unmet clinical need, despite evidence provided by patients and clinicians of substantial disease burden and limitations of currently reimbursed therapies.
CDEC gave little to no consideration to the low economic risk of public reimbursement of roflumilast 0.15% w/w cream as the CDA-AMC deliberative process stops once the submitted product is deemed to not provide clinical value.
In the meeting to discuss the sponsor’s request for reconsideration, CDEC considered the following information:
information submitted as part of the sponsor’s request for reconsideration
information from the initial submission related to the issues identified by the sponsor
feedback from 2 clinical specialists with expertise diagnosing and treating patients with AD
feedback on the draft recommendation from 1 patient group, the Eczema Society of Canada
feedback on the draft recommendation from 1 clinician group, the Dermatology Association of Ontario
feedback on the draft recommendation from the public drug programs that participate in the reimbursement review process
feedback on the draft recommendation from the sponsor.
Dr. Peter Jamieson (Chair), Dr. Kerry Mansell (Vice-Chair), Sally Bean, Daryl Bell, Dan Dunsky, Dr. Ran Goldman, Dr. Trudy Huyghebaert, Dr. Dennis Ko, Dr. Christine Leong, Dr. Alicia McCallum, Dr. Srinivas Murthy, Dr. Nicholas Myers, Dr. Krishnan Ramanathan, Dr. Marco Solmi, Carla Velastegui, Dr. Edward Xie, and Dr. Peter Zed.
Meeting date: October 22, 2025
Regrets: Two expert committee members did not attend.
Conflicts of interest: None
Dr. Peter Jamieson (Chair), Dr. Kerry Mansell (Vice-Chair), Sally Bean, Daryl Bell, Dan Dunsky, Dr. Ran Goldman, Dr. Trudy Huyghebaert, Dr. Dennis Ko, Dr. Christine Leong, Dr. Alicia McCallum, Dr. Srinivas Murthy, Dr. Nicholas Myers, Dr. Krishnan Ramanathan, Dr. Marco Solmi, Carla Velastegui, Dr. Edward Xie, and Dr. Peter Zed.
Meeting date: March 26, 2026
Regrets: Two expert committee members did not attend.
Conflicts of interest: None
ISSN: 2563-6596
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