Análise farmacoepidemiológica e farmacoeconômica dos medicamentos inibidores do fator de necrose tumoral para o tratamento da artrite psoriásica no Sistema Único de Saúde

Abstract

Introduction: psoriatic arthritis (PsA) is a chronic inflammatory disease that can affect multiple joints and is associated with psoriasis. It presents low prevalence and results in a significant functional disability and a decrease in the quality of life of patients affected. The first biological agents included in the Brazilian National Health System (SUS) for the treatment of PsA were inhibitors of tumor necrosis factor (anti-TNF), infliximab, adalimumab and etanercept. However, these drugs were not previously analyzed for their effectiveness, safety and cost-effectiveness in the treatment of PsA under the SUS perspective. Objectives: to analyze the profile of medication request for the treatment of PsA in Specialized Component of Pharmaceutical Services (SCPS) of the SUS and to demonstrate the stages and the time elapsed in the flow of processes; to evaluate the effectiveness and to describe the side effects to the drugs adalimumab, etanercept and infliximab; to estimate costs and to analyze the medication persistence in the treatment of PsA, and finally; to perform a cost-utility analysis of PsA treatment comparing adalimumab and etanercept. Methods: A non-concurrent prospective study was conducted to verify the time spent between the prescription and dispensing of medicines by SCPS. The total time spent was described by means of median and interquartile range (IQR). The factors associated with the time spent on medication requests were verified through linear regression. The effectiveness and safety in the use of anti-TNF agents were evaluated in an open prospective cohort. Subjects were followed for approximately one year, with interviews at the beginning of treatment, at six and 12 months for evaluation of effectiveness, safety, functionality and quality of life. The activity of the disease was measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Clinical Disease Activity Index (CDAI). The reach of inactive disease by BASDAI and of remission or mild disease activity measured by CDAI was defined as an effectiveness measure. The functionality was evaluated through the Health Assessment Questionnaire (HAQ) and the quality of life by EuroQol 5 dimensions (EQ-5D). The predictors of non-effectiveness were verified by logbinomial regression. The medication persistence and the costs of PsA treatment were identified in a historical cohort, constructed by a deterministic-probabilistic linkage of the databases of the Department of Information Technology of SUS (DATASUS). Treatment discontinuation was defined as absence of dispensation after 90 days of initiation of treatment. Medication persistence was described graphically by means of Kaplan-meier curves and compared by means of the log-rank test. Predictors of medication non-persistence were verified by COX regression. The costs were described by mean and SD in terms of direct costs with anti-TNF agents and other outpatient and inpatient costs. The economic analysis was constructed using a Markov analytical decision model, with a time horizon of five years and discount rate of 5%, from the SUS perspective. Four scenarios were created, with variations in costs, utilities and transition probabilities, and deterministic and probabilistic sensitivity analyzes were performed. Results: The median time between the medical consultation and the first dispensation was 66 days (IQR, 44-90). The processing of the process in the State, which includes the request of the medicine until the authorization of the treatment, was the stage that contributed the most to the total time spent. Factors associated with a longer time for medication supply were prescriptions from clinics and specialty centers, dermatologists, unauthorized processes, and non-persistent patients on treatment in 12 months. In the prospective cohort, no statistically significant differences were observed between the three anti-TNF agents in use in the proportion of patients who achieved good clinical response by BASDAI and CDAI at six and 12 months of followup in the first line of treatment. Patients who used adalimumab and etanercept showed improved clinical measures of disease activity, functionality and quality of life compared to baseline. Patients who achieved good clinical response presented better quality of life compared to those who did not reach good clinical response. The predictors of non-effectiveness by CDAI at 12 months were poorer quality of life, use of infliximab, concomitant use of NSAIDs, and have comorbidity. For BASDAI, the predictors of non-effectiveness were greater functional impairment and use of infliximab. The main adverse reactions were alopecia, headache, site reaction, influenza, asthenia and infections. In the historical cohort, adalimumab (51%) was the most used anti-TNF agent. Individuals on adalimumab had greater medication persistence in relation to etanercept and infliximab (p <0.05). The costs with anti-TNF agents accounted for approximately 90% of total costs and were similar among anti-TNF agents in PsA patients. The predictors of medication non-persistence were females, younger patients, residents in the Northeast and North regions, use of infliximab and etanercept and higher Charlson Comorbidity index. In the economic model, etanercept was the most cost-effective. With a willingness to pay of one gross domestic product per capita, adalimumab becomes the most cost-effective drug in one of four analysis scenarios. The deterministic sensitivity analysis identified that costs were the parameters that most impact the choice of the most cost-effective drug. Probability sensitivity analysis indicated that etanercept is the drug most likely to be cost effective. Conclusion: Reducing the total time spent on medication supply can bring benefits to patients' health and treatment. Effectiveness in treatment with anti-TNF agents has been demonstrated and it has been found that health outcomes are similar among the first-line drugs. However, a significant portion of the patients did not reach the expected response, which indicates the need for new treatment approaches. The anti-TNF agents were well tolerated and showed wellestablished adverse events. Medication persistence was lower than in other countries. Etanercept was the most cost-effective drug. A considerable price reduction of anti-TNF agents has been observed over the years. This reinforces the role of costs as an important factor to be evaluated in relation to cost-effectiveness or cost-utility of these drugs and points to the benefits of price renegotiation for the allocative efficiency in public management.