ADHERENCE AND PERSISTENCE TO TREATMENT WITH INFLIXIMAB: ANALYSIS OF A PATIENT SUPPORT PROGRAM COHORT IN BRAZIL.

BACKGROUND: Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics. OBJECTIVE: The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil. METHODS: Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%). RESULTS: A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease. CONCLUSION: Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.

Adesão e persistência ao tratamento com infliximabe: análise de uma coorte de um programa de suporte ao paciente no Brasil / Adherence and persistence to treatment with infliximab: analysis of a patient support program cohort in brazil

ABSTRACT Background: Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics. Objective: The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil. Methods: Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%). Results: A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease. Conclusion: Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.

RESUMO Contexto: Os anticorpos monoclonais têm eficácia comprovada no manejo de diversas condições e o infliximabe (IFX) é um dos medicamentos mais importantes da classe. Alguns dados recentes demonstram baixas taxas de persistência e adesão a vários dos biológicos disponíveis. Objetivo: O objetivo deste estudo foi descrever a adesão e persistência ao tratamento com IFX e a persistência no programa de suporte ao paciente (PSP), entre pacientes diagnosticados com doenças inflamatórias intestinais (DII) ou doenças reumáticas (DR) inscritos no PSP de uma grande indústria farmacêutica no Brasil. Métodos: Análise observacional retrospectiva utilizando o banco de dados do PSP. Pacientes com DII ou DR usando IFX inscritos no banco de dados do PSP entre setembro de 2015 e agosto de 2019 foram avaliados retrospectivamente para identificar a taxa de persistência e adesão e acompanhados até 1º de março de 2020. Os pacientes foram excluídos se a data de início do tratamento fosse anterior à entrada no programa; primeira infusão antes de 1º de setembro de 2015 ou após 31 de agosto de 2019; o paciente não iniciou o tratamento; e pacientes com "OUTROS" no campo "indicação". A persistência foi avaliada considerando tanto a persistência no programa ("persistência PSP") quanto a persistência em uso de infliximabe no PSP ("persistência IFX no PSP"). A persistência no PSP foi definida como a proporção de pacientes que permaneceram no programa aos 6, 12, 24, 36 e 48 meses após o início do IFX. Para determinar a persistência do IFX no PSP, a censura foi definida quando o paciente deixou o programa, morreu ou perdeu o acompanhamento. A adesão ao tratamento foi medida pela razão de posse do medicamento (MPR)): todos os dias de fornecimento / decorridos da primeira prescrição ao último dia de posse do medicamento). A estatística descritiva foi inicialmente utilizada. A curva de Kaplan-Meier, o tempo mediano estimado pela função de sobrevida, o modelo de regressão de Cox e o tempo de sobrevida médio restrito (RMST) foram utilizados para avaliar o tempo de persistência do tratamento em 24 meses e o modelo de regressão logística foi realizado para identificar variáveis associadas à adesão (MPR ≥80%). Resultados: Foram analisados 10.233 pacientes, 5.826 (56,9%) com diagnóstico de DR e 4.407 (43,1%) de DII. Ao final do seguimento (mediana de 9,1 meses desde a entrada no PSP até a última infusão), a persistência no PSP foi de 65,6%, 48,2%, 31,0%, 20,7% e 13,1% aos 6, 12, 24, 36 e 48 meses, respectivamente. Considerando a persistência no IFX no PSP, as estimativas foram de 93,7%, 87,8%, 77,0%, 62,4% e 53,0% aos 6, 12, 24, 36 e 48 meses, respectivamente. As variáveis associadas ao risco de não persistência foram sexo, região do país e diagnóstico de artrite reumatoide e espondilite anquilosante. A mediana do MPR foi de 94,2%, enquanto o percentual de pacientes com MPR ≥80% foram de 91,0%. As variáveis associadas a MPR ≥80% foram região do país e diagnóstico de doença de Crohn. Conclusão: Muitos pacientes abandonam o programa sem interromper o IFX, pois a persistência em 12 meses foi muito diferente entre as estimativas do programa e da medicação, enquanto altas taxas de adesão foram observadas entre os pacientes inscritos no PSP. Os dados destacam os benefícios de um PSP.