Estratégia de troca entre agentes anti-TNF-alfa não melhora a capacidade funcional em pacientes com artrite reumatoide de longa evolução

Abstract

Objectives:To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents in patients with rheumatoid arthritis (RA). Patients and methods: This study included 99 patients diagnosed with RA (American College of Rheumatology, 1987), on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T) or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28) occurred (inadequate response: IR). In case of IR, the patient was considered as primary failure (PF). Secondary failure (SF) was defi ned as loss of response after initial improvement. Remission (DAS28 < 2.6), low disease activity (between 2.61 and 3.2), and functional improvement [increase in the initial Health Assessment Questionnaire (HAQ) > 0.2] were assessed by use of linear regression analysis. The signifi cance level adopted was P < 0.05. Results: Switching was performed in 39 (39.4%) patients, especially due to PF (24.3%), SF (35.1%) and T (40.5%). The retention rate of the fi rst agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After switching, a tendency towards a decrease in DAS28 was observed (4.7 ± 1.4; P = 0.08), but not in the HAQ (1.2 ± 0.77; P = 0.11). Around 43% of the patients achieved good/moderate EULAR response. The major determinant of switching was a higher initial DAS28, independent of age, duration of disease, and functional capacity. Conclusion: Switching between anti-TNF-alpha agents is a valid strategy to control disease activity, despite the low likelihood of remission and no signifi cant improvement in functional capacity.

Profile of patients with rheumatic diseases undergoing treatment with anti-TNF agents in the Brazilian Public Health System (SUS), Belo Horizonte - MG

“…The similar mean disease duration found in the present study and in the BIOBADABRASIL study demonstrate that there is a trend within the Brazilian population regarding the average time that it takes to begin treatment with biological agents. Another Brazilian study (Soares et al, 2012) with RA patients obtained a mean age and prevalence of women similar to the present study. However, that study had higher mean disease duration.…”

Introducing Patterns of Variability for Overcoming Compensatory Adaptation of the Immune System to Immunomodulatory Agents: A Novel Method for Improving Clinical Response to Anti-TNF Therapies

“…The retention of the first agent was 60%, and the mean time to switching was 14 months. After switching, there was a tendency toward decreased DAS28, and 43% of patients had good/moderate EULAR response; however, there was a low likelihood of remission and no significant improvement in functional capacity (75). In a trial of 300 patients with RA with persistent disease activity [DAS28–erythrocyte sedimentation rate (DAS28-ESR) ≥ 3.2] and insufficient response to anti-TNF therapy, patients were randomly assigned to receive a non-TNF targeted biologic agent or to switch to another anti-TNF.…”

Mapeamento de peptídeos ligantes ao receptor do fator de necrose tumoral alfa

“…domínio de ligação do TNF-α ao seu receptor é de grande interesse para a farmacologia. Essa molécula juntamente com o seu receptor é alvo de diferentes medicamentos como infliximab, etarnercept, adalimumab, certolizumab, golimumab como antagonistas do receptor e Tasonermin como agonista, todos já aprovados pelo Food and Drug Administration (FDA)(Croft et al, 2013).No entanto esses medicamentos são moléculas grandes o que facilita a indução no paciente de anticorpos neutralizantes anti-medicamento resultando em perda de atividade.O desenvolvimento de moléculas imunobiológicas, tais como peptídeos moduladores da resposta imune, poderá contribuir para redução dessa resistência ao medicamento principalmente devido ao tamanho reduzida dessa molécula(Keystone, 2006;Soares et al, 2012).Este estudo foi desenhado para selecionar peptídeos ligantes ao receptor de TNF-α na busca por novos imunomoduladores. A tecnologia de Phage Display é excelente para seleção de peptídeos ligantes a diferentes receptores(Koivunen et al, 1999;Odermatt et al, 2001).O uso da biblioteca conformacional de 7 aminoácidos favorece a seleção de novas moléculas, visto que os peptídeos quando sintetizados terão uma conformação mais próxima do alvo, que possibilita a estabilidade, bem como manter sua resposta semelhante de quando analisado em fusão com as proteínas do fago.…”