Modelling the cost-effectiveness of combination therapy for early, rapidly progressing rheumatoid arthritis by simulating the reversible and irreversible effects of the disease

Abstract

ObjectiveTo estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function.MethodsA microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs).ResultsWhen both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106 207 for a resulting incremental cost/QALY gain of £32 425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27 238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78 809 (when only direct costs were included).ConclusionsStarting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered.

Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis

“…The long-term treatment duration in the majority of the simulation models is based on real-world registry data, extrapolated using survival models with time to treatment discontinuation as outcomes. The endpoint driving cost-effectiveness models in RA is primarily physical functioning, whereas other endpoints such as radiographic progression are rarely used [ 76 ].…”

Cost‐Effectiveness of Combination Disease‐Modifying Antirheumatic Drugs Versus Tumor Necrosis Factor Inhibitors in Active Rheumatoid Arthritis: A Pragmatic, Randomized, Multicenter Trial

“…More commonly, modeling‐based rather than trial‐based studies have been used to justify the higher treatment cost of TNFi and other biologics by showing prevention of, or slowed, RA progression over longer time periods. For example, Stephens et al (33) examined combination adalimumab (TNFi) plus methotrexate (DMARD) versus methotrexate alone for patients with early aggressive RA in a 30‐year simulation based on data from a short‐term clinical trial (PREMIER), concluding cost savings and thus cost‐effectiveness when accounting for irreversible radiographic damage and lost productivity costs.…”

Assessing the Value of Sarilumab Monotherapy for Adults with Moderately to Severely Active Rheumatoid Arthritis: A Cost-Effectiveness Analysis

“…RESULTS: Over a lifetime time horizon, a treatment pathway starting with sarilumab resulted in 17.16 life-years and 13.66 quality-adjusted life-years (QALYs). Treatment pathways starting with the cDMARD resulted in 16.54 life-years and 11.77 QALYs; treatment pathways starting with adalimumab resulted in 17.05 life-years and 13.35 QALYs. Total costs for sarilumab ($492,000 for payer perspective, $634,000 for societal perspective) were less than total costs for adalimumab ($536,000 for payer perspective, $689,000 for societal perspective) but higher than total costs for the cDMARD ($63,000 for payer perspective, $272,000 for societal perspective).…”

“…14,15 In addition to relating ACR response to the HAQ score, the model framework related the HAQ score to joint damage and radiographic progression, as measured through the modified TSS (mTSS). 16 Thus, HAQ scores were simulated through separate contributions of ACR and mTSS, given baseline characteristics of the cohort. A lower HAQ score suggests lower RA disease activity and better overall functioning.…”