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Economic Evaluation of Selected Interleukin Inhibitors Versus Methotrexate for Moderate-to-Severe Plaque Psoriasis, From the Philippine Payer Perspective

Open AccessPublished:January 11, 2023DOI:https://doi.org/10.1016/j.vhri.2022.12.001

      Highlights

      • The efficacy and safety of targeted immunological therapy for patients with moderate-to-severe chronic plaque psoriasis has been robustly demonstrated. Nevertheless, biologics remain underutilized in the Philippines.
      • Most economic evaluations of biologics are from settings where other biologics are reasonable comparators. Our evaluation incorporates Philippine clinical practices that accommodate inadequate patient access to expensive treatments.
      • Ixekizumab and secukinumab both appear to be cost-effective treatments for biologic-naive patients with moderate-to-severe chronic plaque psoriasis, relative to methotrexate and the other interleukin inhibitors included in the study.
      • Subsidizing secukinumab treatment would be more expensive to a Government of the Philippines payer than similar subsidies for methotrexate.

      Abstract

      Objectives

      We conducted an economic evaluation of interleukin inhibitors (ILIs) guselkumab, ixekizumab (IXE), secukinumab (SEC), and ustekinumab to a methotrexate (MTX) comparator for biologic-naive adult Filipino patients with moderate-to-severe chronic plaque psoriasis.

      Methods

      A 1-year decision tree and 5-year Markov model were used to estimate incremental cost-effectiveness ratios (ICERs) in Philippine pesos (PHP) per Psoriasis Area Severity Index improvement of at least 75%. For health technology assessment purposes, we also estimated the budget impact of subsidies for SEC to a Government of the Philippines (GoP) payer. Deterministic and probabilistic sensitivity analyses were performed. Data sources included global literature and local intervention prices.

      Results

      All ILIs were more effective but also more expensive than MTX. In the base case, only IXE and SEC were cost-effective treatments at a gross domestic product–benchmarked threshold, yielding ICERs of PHP468 098.01 and PHP483 525.32 per PASI responder, respectively. GUS and UST were less likely to be cost-effective throughout a range of simulated thresholds. ICERs were most responsive to discontinuation rates and drug prices. Full subsidy of SEC for 5 years would cost the GoP PHP1.83 billion more than a similar subsidy for MTX.

      Conclusions

      ILIs were clearly more effective than MTX, but only IXE and SEC were potentially cost-effective for a GoP payer. Any case in which SEC is fully subsidized is more expensive to the GoP than the base case. This study was limited by a lack of country-specific effectiveness data, underestimation of comparator costs, exclusion of noncutaneous and quality-of-life effects, and indirect costs.

      Keywords

      Introduction

      Psoriasis is one of the most common immune-mediated disorders in humans. Estimates of psoriasis prevalence among adults in the Philippines range from 0.22% to 2.4%.
      Atlas, prevalence of psoriasis.
      ,
      • Greb J.E.
      • Goldminz A.M.
      • Elder J.T.
      • et al.
      The course of the disease is typically lifelong, unpredictable, and relapsing. Chronic plaque psoriasis is the most common clinical phenotype, accounting for 55% to 60% of adult cases.
      • Merola J.F.
      • Li T.
      • Li W.Q.
      • Cho E.
      • Qureshi A.A.
      Prevalence of psoriasis phenotypes among men and women in the USA.
      The disorder is marked by a complex inflammatory process largely mediated by dendritic cells and T-cells.
      • Griffiths C.E.
      • Barker J.N.
      Pathogenesis and clinical features of psoriasis.
      Key cytokines include interferon-γ, interleukin (IL)-23, IL-17, and tumor necrosis factor (TNF).
      In the Philippines, moderate-to-severe chronic plaque psoriasis (MSPP) is typically treated with topicals and first-line systemic therapies, such as methotrexate (MTX), ciclosporin, acitretin, and etretinate. Other systemic therapies such as interleukin inhibitors (ILIs) and anti-TNFs are also available. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF-α have been shown to be significantly more effective than small molecules, conventional systemic agents, and placebo in terms of reaching Psoriasis Area Severity Index (PASI)-90.
      • Sbidian E.
      • Chaimani A.
      • Garcia-Doval I.
      • et al.
      Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
      Despite demonstrated efficacy and safety, ILIs continue to be an underutilized treatment option for MSPP in the Philippines. A 2016 facility-based study in the southern Philippines found that only 6.1% of patients with psoriasis were given biologics, with most being given topical steroids (96.9%). MTX was the most common systemic treatment (24.4%).
      • Ng J.N.C.
      • Guevara B.E.G.
      • Guillano V.P.
      Demographic and clinical profiles of adult Filipino patients with psoriasis in Davao City: a cross sectional study.
      Payments for cutaneous psoriasis are borne largely out-of-pocket by Filipinos. Psoriatic arthritis is the only psoriasis-related condition covered by the National Health Insurance Program or PhilHealth, the Philippine government’s social health insurance.
      Resolution Urging the Philippine Health Insurance Corporation (PhilHealth) to include Psoriasis in the List of Diseases and Ailments covered by its healthcare program, with the end in view of making psoriasis treatment available, especially to the margins, HR00719, 17th Congress, 1st Session. Republic of the Philippines House of Representatives, Quezon City.
      Furthermore, MTX is the only systemic psoriasis drug included in the Philippine National Drug Formulary, a list of drugs considered essential drugs by the Department of Health (DOH).
      Philippine national drug formulary: essential medicines list. 8th edition. Republic of the Philippines Department of Health Pharmaceutical Division.
      Other possible funding sources are not universally available, sporadic, or have prohibitive treatment failure stipulations. Many patients are unable to afford the out-of-pocket costs for treatments that may be more effective but also more expensive.
      • Roda A.R.
      Pushing psoriasis as a public health program. HEALTHbeat.
      To the authors’ knowledge, there are no published economic evaluations of the ILIs specific to the Philippine setting. Most economic evaluations of this drug class have been done in developed countries using other biologics as comparators, which is appropriate given the wide access that patients have to treatment options in those contexts.
      • Feldman S.R.
      Treatment of psoriasis in adults. UpToDate.
      Public summary: secukinumab; Cosentyx®. Novartis Pharmaceuticals Australia Pty Ltd.
      Secukinumab for treating moderate to severe plaque psoriasis. National Institute for Clinical Excellence (NICE).
      Single technology appraisal: guselkumab for treating active psoriatic arthritis after inadequate response to DMARDs. National Institute for Health and Care Excellence.
      In this study, we compared the 6-year cost-effectiveness of the 4 ILIs available in the Philippines at the time of writing—guselkumab (GUS) 100 mg/mL, ixekizumab (IXE) 80 mg/mL, secukinumab (SEC) 150 mg/mL, and ustekinumab (UST) 45 mg/mL—in comparison with MTX 2.5 mg tablet, the local status quo systemic treatment for MSPP, from the perspective of a Government of the Philippines (GoP) payer. We also assessed the budget impact to the GoP of providing subsidies for SEC to the eligible Philippine MSPP population. This study was done to compile evidence in preparation for submission of SEC for national health technology assessment processes.

      Methods

      Patient Population and Interventions

      We considered biologic-naive adult patients with active MSPP with demonstrated suboptimal response to a 12-week trial of topicals and systemic nonbiologics. Exclusion criteria were adopted from landmark trials for the included drugs: CHAMPION for MTX,
      • Saurat J.-H.
      • Stingl G.
      • Dubertret L.
      • et al.
      Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION).
      VOYAGE-2 for GUS,
      • Reich K.
      • Armstrong A.W.
      • Foley P.
      • et al.
      Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial.
      UNCOVER-1 for IXE,
      • Gordon K.B.
      • Blauvelt A.
      • Papp K.A.
      • et al.
      Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis.
      FIXTURE for SEC,
      • Langley R.G.
      • Elewski B.E.
      • Lebwohl M.
      • et al.
      Secukinumab in plaque psoriasis - results of two phase 3 trials.
      and PHOENIX-2 for UST.
      • Papp K.A.
      • Langley R.G.
      • Lebwohl M.
      • et al.
      Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
      Treatment regimens were taken from trial regimens and manufacturer information and were confirmed by an expert panel to be identical to those used in local clinical practice. Treatment options and regimens are summarized in Appendix Table 1 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001.

      Model Structure

      This study applied a cohort model combining a 52-week decision tree with a 5-year deterministic Markov model with semiannual cycling. The model (Fig. 1) is a locally contextualized adaptation of the expanded treatment model developed by Graham and associates,
      • Graham C.
      • Mollon P.
      • Miles L.
      • McBride D.
      A new cost-effectiveness framework for modeling psoriasis treatments.
      derived from the York model.
      • Woolacott N.
      • Hawkins N.
      • Mason A.
      • et al.
      Etanercept and efalizumab for the treatment of adults with psoriasis.
      Our model was differentiated by incorporating prevailing local practice compensating for inadequate patient access, including the use of MTX as a comparator, step-down treatments, and adding MTX back into the biologic regimen in case of suboptimal response to monotherapy.
      Figure thumbnail gr1
      Figure 1Structure of the decision tree model.
      BSC indicates best supportive care; ILI, interleukin inhibitor; MTX, methotrexate; PR, PASI response; SAE, serious adverse event; Tx, treatment; Wk, week.
      The response measure we applied was an improvement in PASI of at least 75% from baseline, or PASI 75.
      • Mrowietz U.
      • Elder J.T.
      • Barker J.
      The importance of disease associations and concomitant therapy for the long-term management of psoriasis patients.
      Although global and dermatological quality-of-life indices or remission durations are used in clinical settings to reflect other aspects of response to therapy,
      • Hankin C.S.
      • Feldman S.R.
      • Szczotka A.
      • Stinger R.C.
      • Fish L.
      • Hankin D.L.
      A cost comparison of treatments of moderate to severe psoriasis.
      we used PASI 75 here because of its wide application in clinical trials as an index of treatment efficacy and its predictable correspondence to clinically meaningful outcome measures,
      • Hägg D.
      • Sundström A.
      • Eriksson M.
      • Schmitt-Egenolf M.
      Decision for biological treatment in real life is more strongly associated with the Psoriasis Area and Severity Index (PASI) than with the Dermatology Life Quality Index (DLQI).
      • Herédi E.
      • Rencz F.
      • Balogh O.
      • et al.
      Exploring the relationship between EQ-5D, DLQI and PASI, and mapping EQ-5D utilities: a cross-sectional study in psoriasis from Hungary.
      • Mattei P.L.
      • Corey K.C.
      • Kimball A.B.
      Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies.
      especially in which PASI 90 or better is achievable as is often the case with ILIs.
      • Elewski B.E.
      • Puig L.
      • Mordin M.
      • et al.
      Psoriasis patients with Psoriasis Area and Severity Index (PASI) 90 response achieve greater health-related quality-of-life improvements than those with PASI 75-89 response: results from two phase 3 studies of secukinumab.
      In the model, the cohort entered the 52-week tree and was given active treatment consisting of either MTX or ILI monotherapy. Weeks 12 and 24 were assessment points for PASI response or treatment-related serious adverse events (SAEs), defined as those that are life-threatening or result in death, inpatient hospitalization, or persistent or significant disability.
      Reporting adverse drug reactions: definitions of terms and criteria for their use. Council for International Organizations of Medical Sciences (CIOMS).
      These checkpoints are similar to those in other cost-effectiveness studies on biologics for psoriasis.
      • Woolacott N.
      • Hawkins N.
      • Mason A.
      • et al.
      Etanercept and efalizumab for the treatment of adults with psoriasis.
      ,
      • Knight C.
      • Mauskopf J.
      • Ekelund M.
      • Singh A.
      • Yang S.
      • Boggs R.
      Cost-effectiveness of treatment with etanercept for psoriasis in Sweden.
      ,
      • Graham C.N.
      • McBride D.
      • Miles L.
      • et al.
      Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.
      Responders at any checkpoint were then assumed to continue with active treatment through to week 52. Poor responders to ILI monotherapy at week 12 were given an ILI-MTX combination. SAEs or poor response to MTX at any checkpoint were shifted to best supportive care (BSC) composed of phototherapy and nonactive topicals.
      • Sbidian E.
      • Chaimani A.
      • Garcia-Doval I.
      • et al.
      Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
      ,
      • Papp K.A.
      • Langley R.G.
      • Lebwohl M.
      • et al.
      Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
      Cohorts entered a 5-year Markov model with semiannual cycling in active treatment or BSC (Fig. 2). Although the York model applied a 10-year time horizon, there was, at the time of writing, no clinical guidance recommending continued use through 10 years for biologics. In the Markov model, individuals in active treatment state either remain stable, pass to the absorptive state, or experience one of the transitional or tunnel states. Individuals who entered a transitional state did not remain in that state for the duration of the cycle but instead incurred the costs associated with the transitional event and then passed directly into BSC in the following cycle. Individuals in BSC were assumed to no longer return to active treatment for the duration of the time horizon.
      Figure thumbnail gr2
      Figure 2Structure of the Markov model.
      BSC indicates best supportive care; ILI, interleukin inhibitor; MTX, methotrexate; SAE, serious adverse event; Tx, treatment.
      The health states and transition probabilities for SEC in the cost-effectiveness analysis (CEA) model were also used to estimate the budget impact analysis (BIA) model, which had a time horizon of 5 years in keeping with the administrative life cycle of the GoP.

      Model Inputs

      Clinical inputs

      A focused literature review was done to synthesize available published epidemiologic parameters and clinical outcomes. Sources were primarily economic evaluations, systematic reviews, randomized clinical trials, and observational studies. The resulting input parameters and preliminary economic model were corroborated by consultations with a panel of experts to assess technical soundness and closeness of approximation to Philippine clinical practice conditions.
      The response inputs used in the model were 3-month and 1-year PASI 75 response rates (Appendix Table 2 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). Other clinical inputs included all-cause SAE rates (Appendix Table 3 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001) and all-cause discontinuation rates (Appendix Table 4 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). Response and SAE inputs were extracted from landmark trials. Annual discontinuation rates of 23.4% for SEC and 25% for other biologics was applied, based on a real-world clinical study.
      • Foley P.
      • Tsai T.F.
      • Rodins K.
      • et al.
      Effectiveness and safety of secukinumab for psoriasis in a real-world clinical setting in the Asia-Pacific and Middle East Regions: results from the REALIA study.
      All proportions sourced from the literature were then converted to semiannual transition probabilities using a standard formula.
      • Gidwani R.
      • Russell L.B.
      Estimating transition probabilities from published evidence: a tutorial for decision modelers.

      Cost inputs

      In the absence of local clinical practice guidelines for psoriasis, resource use was estimated from clinical practice guidelines of the US Joint American Academy of Dermatology and the National Psoriasis Foundation and manufacturer-supplied product information.
      • Menter A.
      • Strober B.E.
      • Kaplan D.H.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.
      • Menter A.
      • Gelfand J.M.
      • Connor C.
      • et al.
      Joint AAD-NPF guidelines of care for the management of psoriasis with systemic non-biological therapies.
      • Elmets C.A.
      • Lim H.W.
      • Stoff B.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with phototherapy.
      Ustekinumab: indication, dosage, side effect, precaution. MIMS Philippines.
      Scapho full prescribing information, dosage & side effects. MIMS Philippines.
      Ixekizumab: indication, dosage, side effect, precaution. MIMS Philippines.
      All foreign guidelines were confirmed by local experts to be the same regimens applied by Philippine dermatologists. We estimated only direct medical costs for each of the treatment arms, including consultation fees, costs of treatments/medications, and the costs of screening, diagnosis, and monitoring. Drug acquisition costs (Appendix Table 5 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001) were taken from public sources including the DOH maximum retail price, the DOH Philippine Drug Price Reference Index,
      The 2021 Philippine Drug Price Reference Index, 9th edition. Republic of the Philippines Department of Health – Pharmaceutical Division.
      and manufacturer-validated Philippine retail prices. Other components of the total costs were taken from published charity prices at government facilities (Appendix Tables 6a, b in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). Inpatient treatment costs for SAEs were taken from the Philippine Health Insurance Corporation’s current case rates for major cardiovascular events, nonmelanoma skin cancer, malignancies other than nonmelanoma skin cancer, and severe infections, including sepsis, tuberculosis, pneumonia, skin and soft tissue infections, and urinary tract infections (Appendix Table 7 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). All costs were tallied in Philippine pesos (PHP).

      Other inputs

      Without local epidemiological data on MSPP, initial populations for the budget impact model were taken from the 2020 mid-year adult population of the Philippines to which we applied adult psoriasis prevalence rates for Southeast Asia from the Bayesian hierarchical model of Parisi et al
      • Robinson S.
      • Moon T.M.
      • Zhenli K.
      • et al.
      The Tenth Report of the Malaysian Psoriasis Registry, 2007-2018. DermWeb.
      and adult psoriasis incidence rates from the 2007-2018 Malaysian Psoriasis Registry.
      • Robinson S.
      • Moon T.M.
      • Zhenli K.
      • et al.
      The Tenth Report of the Malaysian Psoriasis Registry, 2007-2018. DermWeb.
      Updated population projections based on the 2015 census of population and housing (POPCEN). Philippine Statistics Authority.
      • Parisi R.
      • Iskandar I.Y.K.
      • Kontopantelis E.
      • et al.
      National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study.
      The proportion of moderate-to-severe psoriasis was derived from large US and UK population-based studies.
      • Yeung H.
      • Wan J.
      • Van Voorhees A.S.
      • et al.
      Patient-reported reasons for the discontinuation of commonly used treatments for moderate to severe psoriasis.
      ,
      • Strober B.
      • Karki C.
      • Mason M.
      • et al.
      Characterization of disease burden, comorbidities, and treatment use in a large, US-based cohort: results from the Corrona Psoriasis Registry.
      Potential dropouts were accounted for by applying discontinuation rates from the cost-effectiveness model. The base case and scenario treatment mixes were derived from a Philippine facility-based observational study,
      • Ng J.N.C.
      • Guevara B.E.G.
      • Guillano V.P.
      Demographic and clinical profiles of adult Filipino patients with psoriasis in Davao City: a cross sectional study.
      manufacturer-supplied data, and panel-validated assumptions. Inputs to the budget impact model are summarized in Appendix Table 8 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001.

      Base-Case Analysis

      Cost-Effectiveness of ILIs

      Despite the chronic nature of plaque psoriasis, the primary cost outcome was total direct medical costs over 6 years because at the time of writing, there was no locally accepted guidance for long-term treatment of MSPP with biologics. The health outcome was measured in PASI responders from which we estimated the incremental cost-effectiveness ratio (ICER) for each ILI versus MTX, in PHP per PASI responder. In the Philippines, at the time of this writing, there was no consensus on the appropriate threshold of societal willingness-to-pay (WTP) for health interventions; we used a proxy equal to 3 times the Philippine per capita gross domestic product (GDP) in 2020, or PHP491 104.01.
      GDP per capita (current US$) - Philippines. DataBank. The World Bank Group.
      We also assessed thresholds of 1- and 2-times per capita GDP. An annual discount rate of 7% was applied to future costs and outcomes in the CEA base case, as recommended by the Philippine Health Technology Assessment Council for time horizons below 30 years.
      Philippine HTA methods guide
      Republic of the Philippines Department of Health - Health Technology Assessment Unit.

      Budget impact of SEC

      The base case for the SEC budget impact model examines the estimated cost to the GoP of a status quo treatment mix over 5 years. The eligible population for systemic therapy was used to derive expected populations of MTX and SEC users, taking account of market share growth and treatment shifting. Treatment costs included drug costs, consultations, monitoring, and inpatient treatment of SAEs. For the base case, we considered the MTX scenario (ScM), simulating the effect of full funding only for MTX and SAEs, and no funding for SEC. ScM approximates current health system conditions in which SEC acquisition costs are almost entirely out of the pocket.

      Sensitivity Analysis

      We performed deterministic one-way sensitivity analyses (OWSAs) and a probabilistic sensitivity analysis (PSA) to investigate uncertainty in the base-case model. The OWSA systematically varied technology costs, discontinuation rates, discount rates, response rates, and the probability of SAEs between low and high values to determine the main drivers of the base-case ICER (Appendix Table 9 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). Lower bounds for sensitivity analysis of all medical costs were patterned after Philippine national discount rates for senior citizens and persons with disability. The PSA involved calculating ICERs for all ILIs through 10 000 Monte-Carlo simulations, sampling repeatedly from the distributions of all input parameters to account for uncertainties surrounding the input parameters (Appendix Table 10 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). Net monetary benefits were plotted on a cost-effectiveness acceptability curve (CEAC) over a range of values representing the GoP’s WTP for the ILIs over MTX.

      Results

      Base-Case Results

      Over a 6-year time horizon, our base-case analysis showed that only IXE and SEC are potentially cost-effective to a GoP payer for biologic-naive patients with MSPP in the Philippines (Table 1). Per patient over 6 years, monotherapy with MTX costs PHP236 134.93 compared with up to PHP1.7 million for IXE, the least expensive ILI. In contrast, the effectiveness of MTX, estimated at only 675 PASI responses, was far inferior to the PASI responses estimated for any ILI. IXE was the most cost-effective ILI in the base case, with an ICER of PHP468 098.01 per response, followed by SEC with an ICER of PHP483 525.32 per response. The effectiveness of GUS and UST were highly similar to that of IXE and SEC, but higher unit drug prices for the former pushed their cost-effectiveness lower than the latter.
      Table 1ICERs, base-case analysis.
      TreatmentCost per capita, PHPPASI 75 responsesICER (per response gained)CE rank
      Comparator
       MTX236 134.93675
      IL inhibitors
       GUS2 232 843.553999600 827.104
       IXE1 661 326.303720468 098.011
       SEC1 812 283.093935483 525.342
      UST1 990 689.663857551 512.063
      Note. All costs are in 2020/2021 PHP (₱).
      CE indicates cost-effective; GUS, guselkumab; ICER, incremental cost-effectiveness ratio; IL, interleukin; IXE, ixekizumab; MTX, methotrexate; PASI, Psoriasis Area Severity Index; PHP, Philippine pesos; SEC, secukinumab; UST, ustekinumab.
      The BIA base case for SEC (Table 2) showed that, over a 5-year time horizon with full subsidy for MTX and SAEs, but no funding for SEC active treatment, the GoP would face a total impact of about PHP123.21 million. The budget impact would total about PHP1.95 billion if funding were shifted entirely to SEC, and it would be about PHP2.04 billion if both MTX and SEC were fully subsidized by the payer.
      Table 2Budget impact of SEC for a Philippine government payer.
      ScenarioDescriptionFive-year budget impact, PHPNet budget impact relative to base case, PHP
      Base case: ScMPayer fully funds all treatment costs for MTX only and pays the case rate for inpatient treatment of SAEs.123 209 677.84Reference
      ScSPayer fully funds all treatment costs for SEC only and pays the case rate for inpatient treatment of SAEs.1 953 378 856.191 830 169 178.36
      ScMSPayer fully funds all treatment costs for both MTX and SEC and pays the case rate for inpatient treatment of SAEs.2 044 580 567.111 921 370 889.28
      ScMS-FSame as ScMS, but some patients who discontinue with MTX shift to SEC.2 391 428.210.842 268 218 533.00
      ScMS-FVSame as ScMS-F, with accounting for market share value growth of SEC.2 399 540 462.572 276 330 784.73
      Note. All costs are in 2020/2021 PHP (₱).
      MTX indicates methotrexate; PHP, Philippine pesos; SAE, serious adverse event; SEC, secukinumab.

      Sensitivity Analysis

      The results of the PSA for the ILIs versus MTX are summarized in the CEACs shown in Figure 3. At a 3-times-GDP threshold, IXE and SEC provided net monetary benefits greater than MTX for biologic-naive patients with MSPP in 29.89% and 30.38% of simulations, respectively, and were more likely to be preferred to MTX at any WTP threshold ≥ PHP270 000.00, or about 1.6-times GDP. Both were more likely to be cost-effective than GUS and UST throughout the range of simulated thresholds. Scatterplots of the simulation results (Appendix Fig. 1 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001) showed concentration of ICERs within the northeast quadrant of the cost-effectiveness plane for all ILIs, affirming their higher effectiveness and higher costs relative to the MTX comparator. The deterministic sensitivity analyses showed that ICERs for all ILIs were most responsive to discontinuation rates, drug costs, and response rates (Appendix Fig. 2 in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001). MTX-specific inputs and SAE rates had only minimal effects on ICER estimates.
      Figure thumbnail gr3
      Figure 3Cost-effectiveness acceptability curve.
      GUS indicates guselkumab; IXE, ixekizumab; MTX, methotrexate; PASI, Psoriasis Area Severity Index; PHP, Philippine pesos; SEC, secukinumab; UST, ustekinumab.
      For the BIA, all scenarios estimated yielded net budget impacts that were higher than the base case. The 2-way coverage and subsidy analyses of the ScS scenario, where all SEC treatment costs and case rates for inpatient treatment of SAEs are fully funded, and the ScMS scenario, identical to ScS but with the addition of full funding for MTX (Table 3) (Appendix Tables 11a, b in Supplemental Materials found at https://doi.org/10.1016/j.vhri.2022.12.001) show that both are more costly at full subsidy than the MTX-only scenario. Nevertheless, providing a 10% subsidy for SEC to 10% of the eligible population instead of fully subsidizing MTX is less expensive than the base case by PHP72.04 million. Increasing the 10% subsidy to cover 40% of the SEC-eligible population or subsidizing 40% of the cost for 10% of the population is still less expensive than the base case but decreases net savings to PHP14.39 million. None of the subsidy-coverage combinations in which SEC is funded in addition to MTX is less expensive than the base case.
      Table 3Budget impact 2-way scenario analysis results.
      ScenarioPopulations subsidized
      Number of individuals receiving subsidies for MTX treatment costs, SEC treatment costs, and inpatient treatment of SAEs.
      CombinationsBudget impact, PHP
      MTXSECSAESEC subsidy, %SEC coverage, %
      Refers to the proportion of the population of expected users to which the subsidy would be applied.
      TotalNet
      Relative to the ScM base case.
      Base case: ScM11 076021300123 209 677.84Reference
      ScS
       Lowest
      Combination with the lowest total budget impact.
      0630213101051 167 707.30−72 041 970.53
       Highest affordable
      Affordable means having total cost less than or equal to the total cost of the base case with the highest total budget impact.
      0

      0
      630

      2521
      213

      213
      40

      10
      10

      40
      108 810 469.39

      108 810 469.39
      −14 399 208.45

      −14 399 208.45
      ScMSNo affordable combinations for this scenario
      Affordable means having total cost less than or equal to the total cost of the base case with the highest total budget impact.
      Note. ScM: Payer fully funds all MTX treatment costs and pays the case rate for inpatient treatment of SAEs.
      ScS: Payer fully funds all SEC treatment costs and pays the case rate for inpatient treatment of SAEs.
      ScMS: Payer fully funds all treatment costs of both MTX and SEC, in addition to paying for inpatient treatment of SAEs.
      MTX indicates methotrexate; PHP, Philippine pesos; SAE, serious adverse event; SEC, secukinumab.
      Number of individuals receiving subsidies for MTX treatment costs, SEC treatment costs, and inpatient treatment of SAEs.
      Refers to the proportion of the population of expected users to which the subsidy would be applied.
      Relative to the ScM base case.
      Combination with the lowest total budget impact.
      Affordable means having total cost less than or equal to the total cost of the base case with the highest total budget impact.

      Discussion

      This study sought to undertake a cost-effectiveness analysis of the ILIs GUS, IXE, SEC, and UST relative to an MTX comparator within the Philippine dermatologic practice context. To our knowledge, this is the first study to evaluate the cost-effectiveness of ILIs for MSPP in a resource-constrained setting in which government subsidies to biologic treatment are limited, if not nonexistent, and in which the appropriate status quo treatment is not another biologic.
      Base-case analysis of cost-effectiveness revealed that, although PASI responses with all ILIs were significantly higher than those for MTX, the estimated technology costs were also much higher than the comparator. Despite the similarity of ILIs in effectiveness and safety, only IXE and SEC were cost-effective to a GoP payer at the benchmark WTP threshold in the Philippines. Sensitivity analysis confirmed this result while highlighting the effect of drug prices on cost-effectiveness. The SAE rate for the ILIs also did not significantly affect ICERs values; despite the high costs associated with inpatient adverse events, probabilities were so low that the impact of these costs was nearly negligible. A moderate spread of the simulated estimates is evidence of parameter uncertainty in the base case.
      Several factors contributed to the overall strength of the analysis. Clinical effectiveness data for different treatments were derived from large randomized clinical trials. Direct medical costs used in this analysis were derived from an array of published prices and reflect the true economic burden imposed by MSPP on healthcare payers in the Philippines. The model structure, methodology, and input parameters were validated by an expert panel. Finally, the study results were confirmed by both OWSA and PSA.
      One of the most significant limitations to this study is that we were unable to quantify outcomes in terms of quality-adjusted life-years (QALYs). This may make it difficult for policy planners to assess the cost-effectiveness of this technology beyond the limited clinical sphere within which the analysis was done. Furthermore, the measure of effectiveness itself is limited to the cutaneous aspects of MSPP, disregarding non–PASI-detectable benefits of the biologics, such as for psoriatic arthritis and cardiovascular complications. Subsequent analysis may explore quantifying outcomes in terms of QALYs, whether through a PASI-QALY mapping exercise, secondary data when such become available, or primary data collection if resources permit. Furthermore, the comparator approximated by MTX monotherapy underestimates the true extent and cost of first-line therapies, which generally also include active topical agents, such as corticosteroids, coal tar, anthralin, calcipotriene, and tazarotene, and auxiliary agents, such as keratolytics and emollients. These were not included in the current model because of the difficulty of specifying a true standard of care as these therapies tend to be prescribed in a highly individualized and often rotational manner.
      • Elmets C.A.
      • Lim H.W.
      • Stoff B.
      • et al.
      Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with phototherapy.
      Finally, as this study was from the GoP payer perspective, it does not incorporate societal costs or benefits.

      Conclusions

      Our analysis showed that, for biologic-naive patients with MSPP, all the included ILIs are clearly more effective than MTX for MSPP, but only IXE and SEC are potentially cost-effective for a GoP payer with a WTP threshold ≥ PHP270 000.00. High drug acquisition costs limit the cost-effectiveness of GUS and UST in this population and are the greatest drivers of ICERs for all ILIs included in the study. Full subsidy of SEC, in addition to MTX, by the GoP for 5 years creates an additional budget impact of PHP1.83 billion relative to a scenario in which only MTX is fully funded, not accounting for possible offsets from avoiding SEC-treatable comorbidities and sequelae of MSPP. Decision makers will need to carefully consider all costs and benefits of the ILIs for psoriasis healthcare programs.

      Article and Author Information

      Author Contributions: Concept and design: Almirol, de Guzman, Guce, Kimwell, Malaluan, Mendoza
      Acquisition of data: de Guzman, Dofitas, Frez, Guce, Kimwell, Malaluan, Mendoza, Onda, Rivera
      Analysis and interpretation of data: de Guzman, Dofitas, Frez, Guce, Kimwell, Mendoza, Onda, Rivera
      Drafting of the manuscript: Almirol, de Guzman, Frez, Kimwell, Onda
      Critical revision of the paper for important intellectual content: de Guzman, Kimwell
      Statistical analysis: de Guzman, Kimwell
      Provision of study materials or patients: Guce
      Obtaining funding: Almirol, Malaluan
      Administrative, technical, or logistic support: Almirol, Guce, Malaluan
      Supervision: Guce, Kimwell
      Minor manuscript review and revisions: Dofitas, Rivera
      Conflict of Interest Disclosures: All authors reported receiving personal fees from Novartis Healthcare Philippines, Inc, during the conduct of the study. Drs Frez and Mendoza also reported receiving personal fees from Johnson & Johnson and Zuellig Pharma outside the submitted work. No other disclosures were reported.
      Funding/Support: This research received funding from Novartis Healthcare Philippines, Inc.
      Role of the Funder/Sponsor: The funder assisted in the conduct of the study, in particular, through facilitation of data requests from manufacturers, provision of study materials, and through administrative and logistical support. Publication of study results was not contingent on the sponsor’s approval or censorship of the manuscript.

      Acknowledgment

      The authors would like to thank the participating companies and employees of the study for their cooperation. They are also grateful to Benedict Evangelista Jr for assistance with data collection and Allen Danielle Gonzalez for editorial assistance.

      Supplemental Material

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