Dataset Information

Treatment sequencing after failure of the first biologic in cost-effectiveness models of psoriasis: a systematic review of published models and clinical practice guidelines.

ABSTRACT:

Objectives

To analyse the treatment sequencing assumptions after failure on a first-line biologic in cost-effectiveness models of treatment of moderate to severe plaque psoriasis, and to compare them with the most recent treatment guidelines.

Methods

A systematic search of MEDLINE, Embase, EconLit and the Cochrane Library databases used free text and Medical Subject Headings terms including psoriasis, biologic therapies indicated for psoriasis, and all types of economic evaluations. Two researchers performed 2-level abstract screening for articles meeting pre-specified inclusion criteria. Assumptions about treatment pathways after first-line biologic failure in the cost-effectiveness models were analysed. A second systematic search was performed for psoriasis clinical practice guidelines. Sequence assumptions were compared with treatment guideline recommendations.

Results

Of 25 cost-effectiveness modelling studies identified, ten estimated the incremental cost per responder; time horizons varied (12 weeks-18 months) and treatment sequencing was not considered. In 15 studies where treatment sequencing was considered, with time horizons up to 10 years, five studies included only a switch to nonsystemic therapy or best supportive care after first-line biologic failure. Another five of the 15 treatment-pathway studies were available only as abstracts with no details of the sequence assumptions. In five of the 15 studies, first-line biologic failure was followed by second-line biologic monotherapy, one of the recommendations in current treatment guidelines. In only one of these five studies was the efficacy of the second-line biologic adjusted downwards, compared with first-line treatment. Only one of these studies considered dose titration with a first-line biologic and none combination therapy (biologic plus methotrexate or phototherapy) after first-line biologic failure, as recommended in some treatment guidelines.

Conclusions

Cost-effectiveness models of first-line biologics for moderate to severe plaque psoriasis either do not include subsequent treatment regimens or include only some of the regimens recommended in current treatment guidelines. Results may be sensitive to assumptions about treatment sequencing and the choice and efficacy of subsequent treatment regimens.

SUBMITTER: Mauskopf J

PROVIDER: S-EPMC3964298 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundLittle is known about the treatment outcomes of secukinumab in clinical practice, which differ from those in clinical trials. The effectiveness of biologics may differ in psoriasis patients with previous biologics exposure. The objective of this study was to investigate the real-world effectiveness and safety of secukinumab therapy and analyze subgroups stratified by reimbursement or prior biologic failure.MethodsThis retrospective multicenter study collected data from a cohort of 118 consecutive patients who received secukinumab treatment between December 2015 and March 2018. Effectiveness was evaluated by degree of improvement in the Psoriasis Area and Severity Index (PASI) scores. Adverse events and reasons for discontinuation were also recorded.ResultsThe mean PASI improvement rate at weeks 4, 12, 24, and 36 was 63.5%, 77.7%, 78.7%, and 76.0%, respectively. Compared with reimbursed patients, nonreimbursed patients had a significantly lower baseline PASI and a shorter mean disease duration of psoriasis; they were more frequently biologic-naïve, had used less prior traditional antipsoriatic drugs and were more likely to be treated with secukinumab 150 mg. The effectiveness of secukinumab in nonreimbursed patients was superior despite higher discontinuation rates. Compared with patients without prior biologic failure, patients with prior biologic failure had a significantly lower mean PASI improvement at weeks 12, 24, 36, and 48. The decline in response rates to secukinumab tended to be more pronounced for patients who failed ustekinumab than tumor necrosis factor-α inhibitors. Moreover, the number of prior biologic failures was associated with a decreased response rate and increased likelihood of secondary loss of effectiveness of secukinumab therapy.ConclusionIn a real-life clinical setting, the characteristics of nonreimbursed patients receiving secukinumab treatment differed from those of reimbursed patients. The PASI improvement for secukinumab was substantial but lower than that in clinical trials. The number and classes of prior biologic failures impact the treatment response to secukinumab.

Project description:IntroductionA clinical trial (RACAT) reported the noninferiority of triple therapy compared to biologic agents (etanercept + methotrexate), and previous studies confirmed that biologic disease-modifying antirheumatic drugs (bDMARDs) are more expensive but less beneficial than triple therapy for patients with rheumatoid arthritis (RA) in whom methotrexate (MTX) fails. However, from the perspective of the Chinese healthcare system, the cost-effectiveness of triple therapy versus bDMARD treatment sequences as a first-line therapy for patients with RA is still unclear.MethodsAn individual patient simulation model was used to extrapolate the lifetime cost and health outcomes by tracing patients from initial treatment through switches to further treatment lines in a sequence. Therapeutic efficacy and physical function were evaluated using the American College of Rheumatology (ACR) response, 28-Joint Disease Activity Score (DAS28), and Health Assessment Questionnaire score. All input parameters in the model were derived from published studies, national databases, local hospitals, and experts' opinions. Both direct costs and indirect costs were taken into consideration. Probabilistic and one-way sensitivity analyses were performed to test the uncertainty of the model, as were multiple scenario analyses.ResultsThe lifetime analysis demonstrated that triple therapy was associated with lower costs and quality-adjusted life years (QALYs) than bDMARD sequences. These resulted in incremental cost-effectiveness ratios (ICERs) ranging from $87,090/QALY to $104,032/QALY, higher than the willingness-to-pay (WTP) threshold in China ($30,950/QALY). The baseline DAS28 impacted the model outcomes the most. Scenario analyses indicated that adding triple therapy to bDMARD sequences as a first-, second-, third-, or fourth-line therapy is very cost-effective, at a WTP of $10,316/QALY.ConclusionsFrom a Chinese payer perspective, triple therapy as first-line treatment in treatment sequence could be regarded as cost-effectiveness option for patients who failed MTX, compared to bDMARDs as first-line treatment, and instead of prescribing triple therapy as a substitute for bDMARDs as a first-line treatment, adding triple therapy to the bDMARD treatment sequence is likely to be very cost-effective for patients with active RA compared to bDMARD sequences.

Project description:Clinical guidelines play a central role in day-to-day practice. We assessed the degree of incorporation of cost analyses to guidelines and identified modifiable characteristics that could affect the level of incorporation.We selected the 100 most cited guidelines listed on the National Guideline Clearinghouse (http://www.guideline.gov) and determined the number of guidelines that used cost analyses in their reasoning and the overall percentage of incorporation of relevant cost analyses available in PubMed. Differences between medical specialties were also studied. Then, we performed a case-control study using incorporated and not incorporated cost analyses after 1:1 matching by study subject and compared them by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement requirements and other criteria.We found that 57% of guidelines do not use any cost justification. Guidelines incorporate a weighted average of 6.0% (95% confidence interval [CI] 4.3-7.9) among 3396 available cost analyses, with cardiology and infectious diseases guidelines incorporating 10.8% (95% CI 5.3-18.1) and 9.9% (95% CI 3.9- 18.2), respectively, and hematology/oncology and urology guidelines incorporating 4.5% (95% CI 1.6-8.6) and 1.6% (95% CI 0.4-3.5), respectively. Based on the CHEERS requirements, the mean number of items reported by the 148 incorporated cost analyses was 18.6 (SD?=?3.7), a small but significant difference over controls (17.8 items; P?=?0.02). Included analyses were also more likely to directly relate cost reductions to healthcare outcomes (92.6% vs 81.1%, P?=?0.004) and declare the funding source (72.3% vs 53.4%, P?<?0.001), while similar number of cases and controls reported a noncommercial funding source (71% vs 72.7%; P?=?0.8).Guidelines remain an underused mechanism for the cost-effective allocation of available resources and a minority of practice guidelines incorporates cost analyses utilizing only 6% of the available cost analyses. Fulfilling the CHEERS requirements, directly relating costs with healthcare outcomes and transparently declaring the funding source seem to be valued by guideline-writing committees.

Project description:BackgroundReal-life data on patients with psoriasis treated with guselkumab are few and are needed to compare with trial-based data. We investigated the effect of clinical factors on real-world effectiveness of guselkumab.MethodsThis multicentre study retrospectively included 135 patients with psoriasis treated with guselkumab from June 2018 until November 2020. Effectiveness was assessed using the degree of improvement in the Psoriasis Area and Severity Index (PASI) scores at baseline and after 4, 12, 20, 28, and 36 weeks. Predictors of effectiveness were also evaluated.ResultsAt week 36, 67% of the patients achieved PASI 75. Multivariate logistic regression analysis revealed that heavier patients were less likely to achieve PASI 75 at week 4 than patients with lower body weights. Fewer patients exposed to only one biologic achieved PASI 75 at weeks 4, 20, 28, and 36 [odds ratio (OR) = 0.08 (95% CI, 0.01-0.48), 0.21 (95% CI, 0.05-0.74), 0.04 (95% CI, 0.00-0.35), and 0.07 (95% CI, 0.00-0.68), respectively] than biologic-naïve patients. Patients previously treated with more than one biologic were less likely to achieve PASI 75 at weeks 12, 20, 28, and 36 [OR = 0.05 (95% CI, 0.01-0.22), 0.03 (95% CI, 0.01-0.16), 0.00 (95% CI, 0.00-0.03), and 0.00 (95% CI, 0.00-0.044), respectively] than biologic-naïve patients. Patients with previous anti-interleukin (IL)-17 exposure, rather than tumour necrosis factor-α and IL-12/23 inhibitors, had lower PASI improvements to guselkumab than biologic-naïve patients at weeks 12, 20, and 28 [OR = 0.19 (95% CI, 0.03-0.90), 0.10 (95% CI, 0.02-0.55), and 0.03 (95% CI, 0.00-0.29), respectively].ConclusionsThe effectiveness of guselkumab was compromised in a real-world setting. Delayed onset of therapeutic response was noted in heavier patients. Biologic exposure, the number of previously used biologics, and previous exposure to IL-17 inhibitors were clinical predictors of a reduced response to guselkumab. Physicians may share this information with patients to make treatment decisions.

Project description:IntroductionBiologic agents are used in patients with severe psoriasis who have not adequately responded to existing conventional systemic therapies. However, only a limited number of medical institutions in Japan are approved to use them, and their relatively high cost represents a substantial burden to patients. Apremilast is an oral phosphodiesterase-4 inhibitor approved in Japan for the treatment of psoriasis vulgaris in adult patients with an inadequate response to topical therapies and psoriatic arthritis in adult patients with active disease. To date, a large-scale real-world study of treatment patterns and costs associated with apremilast in Japan has not been conducted. The objective of this study was to assess whether apremilast can prolong time to first biologic therapy use and decrease total medical cost.MethodsUsing the Medical Data Vision hospital-based claims database, 506 psoriasis patients were propensity score matched and analyzed (apremilast: n = 253; non-apremilast: n = 253).ResultsThe incidence rate of first biologic therapy use per 1000 patient-years was significantly lower in the apremilast group than in the non-apremilast group (30.3 vs. 107.6; P < 0.001), and the total medical costs per month were significantly lower in the apremilast group than in the non-apremilast group (76,594 yen/month vs. 102,411 yen/month, P < 0.001). In a sensitivity analysis of a propensity-score-matched subset of eligible patients prescribed biologics during the follow-up period (apremilast: n = 14; non-apremilast: n = 14), the incidence of first biologic therapy use was 2,797.6 per 1000 patient-years (95% CI: 1,656.9, 4,723.6) in the non-apremilast group and 856.1 per 1000 patient-years (95% CI: 507.0, 1,445.5) in the apremilast group.ConclusionThese results suggest that apremilast prolongs the time to first biologic therapy use in patients with psoriasis, thereby reducing the total medical cost and decreasing the economic burden on patients.

Project description:Psoriasis is an inflammatory and chronic skin disorder associated with physical and psychological burden impairing patients' quality of life. In the last decade, biologic drugs have widely changed treatment of moderate-severe psoriasis and their number is increasing overtime. To early identify expected/unexpected adverse events (AEs) with biologic treatments, pharmacovigilance programs are needed. We designed a post-marketing active pharmacovigilance program to monitor and analyse AEs and/or serious adverse events (SAEs) reports. All consecutive patients treated with one biologic drug during a two-years period and satisfying inclusion criteria have been enrolled in five Dermatology tertiary units. Demographic and clinical features of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Overall, 512 patients with a diagnosis of psoriasis (286; 55.9%) or arthropathic psoriasis (226; 44.1%) have been enrolled. Eighty-two (16%) patients with AEs and 5 (1%) with SAEs have been identified. Further, 59 (11.5%) had a primary/secondary failure (mainly on infliximab and etanercept). The adverse events and SAEs were reported with golimumab (4/12), adalimumab (32/167), infliximab (9/48), etanercept (31/175) and ustekinumab (11/73), no adverse events have occurred with secukinumab (0/37). Infliximab and etanercept were significantly associated with primary/secondary failures, whereas no differences have been highlighted for AEs insurgence. On the other hand, ustekinumab seems to be associated with a low rate of AEs (p = 0.01) and no adverse events or failures have been reported with secukinumab (p = 0.04 and 0.03, respectively). Our study, even though limited by a small sample size and a brief follow-up period, provide useful data on widely used biologic drugs and their tolerability, discontinuation rate and the incurrence of severe adverse events. Further studies are necessary to include the recently approved biologic drugs and to increase the sample size for more detailed analysis.

Project description:On the basis of the 2014 guidelines for hypertension therapy in the United States, many eligible adults remain untreated. We projected the cost-effectiveness of treating hypertension in U.S. adults according to the 2014 guidelines.We used the Cardiovascular Disease Policy Model to simulate drug-treatment and monitoring costs, costs averted for the treatment of cardiovascular disease, and quality-adjusted life-years (QALYs) gained by treating previously untreated adults between the ages of 35 and 74 years from 2014 through 2024. We assessed cost-effectiveness according to age, hypertension level, and the presence or absence of chronic kidney disease or diabetes.The full implementation of the new hypertension guidelines would result in approximately 56,000 fewer cardiovascular events and 13,000 fewer deaths from cardiovascular causes annually, which would result in overall cost savings. The projections showed that the treatment of patients with existing cardiovascular disease or stage 2 hypertension would save lives and costs for men between the ages of 35 and 74 years and for women between the ages of 45 and 74 years. The treatment of men or women with existing cardiovascular disease or men with stage 2 hypertension but without cardiovascular disease would remain cost-saving even if strategies to increase medication adherence doubled treatment costs. The treatment of stage 1 hypertension was cost-effective (defined as <$50,000 per QALY) for all men and for women between the ages of 45 and 74 years, whereas treating women between the ages of 35 and 44 years with stage 1 hypertension but without cardiovascular disease had intermediate or low cost-effectiveness.The implementation of the 2014 hypertension guidelines for U.S. adults between the ages of 35 and 74 years could potentially prevent about 56,000 cardiovascular events and 13,000 deaths annually, while saving costs. Controlling hypertension in all patients with cardiovascular disease or stage 2 hypertension could be effective and cost-saving. (Funded by the National Heart, Lung, and Blood Institute and others.).

Project description:BackgroundHeart failure (HF) is a well-recognized public health concern and imposes high economic and societal costs. Decision analytic models exist for evaluating the economic ramifications associated with HF. Despite this, studies that appraise these modelling approaches for augmenting best-practice decisions remain scarce.ObjectiveOur objective was to conduct a systematic literature review (SLR) of published economic models for the management of HF and describe their general and methodological features.MethodsThis SLR employed a combination of relevant search terms associated with HF, which were used in a number of databases, including MEDLINE, Embase, the National Health Service Economic Evaluation Database, Cost-Effectiveness Analysis Registry, ScHARR Health Utilities Database and Cochrane Library Database. A number of model features (i.e. model structure, specification, outcomes assessed, scenario and sensitivity analysis, key model drivers) were extracted and subsequently summarized.ResultsOf 64 publications retained, a selection of modelling approaches were identified, including Markov (n?=?28), trial-based analytic (n?=?22), discrete-event simulation (n?=?6), survival analytic (n?=?7) and decision-tree modelling (n?=?1) approaches. The bulk of publications employed either a cost-utility (n?=?27) or cost-effectiveness (n?=?36) analysis and evaluated more than one study outcome, which typically included overall costs (n?=?59), incremental cost-effectiveness ratios (n?=?55), life-years gained (n?=?48) and willingness-to-pay thresholds (n?=?37). Most publications focused on patients with chronic HF (n?=?40) and used New York Heart Association (NYHA) disease classifications to categorize patients and determine disease severity. Few (n?=?19) publications documented the use of hospitalization states for modelling patient outcomes and associated costs. A quality assessment of the included publications revealed most articles demonstrated reasonable methodological value.ConclusionsWe identified numerous decision analytic modelling approaches for evaluating the cost effectiveness of pharmacologic treatments in HF. A Markov cohort model approach was most commonly used, and most models relied on NYHA classes as a proxy of HF severity, disease progression and prognosis.