AB0384 The Effects of Pentoxifylline on Rheumatoid Arthritis Activity According To The DAS28 CRP Disease Activity Score:

Abstract

BackgroundTreatment of rheumatoid arthritis (RA) prior to “Treat to target” is difficult enough, forcing researchers around the world look for ways to improve the effectiveness of RA treatment.ObjectivesTo explore the possibilities of reducing RA activity on the disease activity score DAS28 CRP by adding pentoxifylline to the methotrexate treatment.MethodsThis study included women (n=101) with RA longer than 1 year in duration, have a seropositive rheumatoid factor, and DAS28 CRP activity score of 3.2–5.1. Middle aged – 45.04±5.24 years old. All patients received a 15.50±2.50 mg oral dose of methotrexate per week. Patients were divided into two groups - those who only had methotrexate (n=50) and those who were treated with an oral dose of methotrexate and 1200 mg of pentoxifylline per day (n=51).ResultsThe baseline for both groups of RA patients did not differ significantly in terms of the level on the DAS28 CRP (p=0.812). On 14th day of the group who were taking pentoxifylline, the DAS28 CRP disease activity score was significantly lower by 12.5% (p<0.001). After 28 days, the users had a DAS28 CRP disease activity score index difference. The difference between two groups is statistically significant. In the group that were treated with pentoxifylline in addition to methotrexate (p=0.001) the index was found to be 8.3% lower. For 28 days, the methotrexate group's disease activity according to the DAS28 CRP activity score significantly decreased by 14.3% from the baseline (p<0.001). For 28 days, the pentoxifylline + methotrexate group also achieved a statistically significant reduction in the index according to the DAS28 CRP activity score by 20.5% (p<0.001)The disease activity index for the two groups for 14 and 28 days is shown in the table.DAS28 CRP Index in the two groups of RA patientsGroups of patients and observation timeGroupGroupStatistical significant differences between the two groupsMethotrexate (n=50)Methotrexate + Pentoxifylline (n=51)Baseline3.11±0.053.13±0.05p=0.812For 14 days3.06±0.052.69±0.06p<0.001For 28 days2.71±0.042.48±0.06p=0.001ConclusionsThus, converting the monotherapy methotrexate to pentoxifylline will significantly reduce the activity of RA, while avoiding many of the adverse effects of the other combination therapies. This data requires further long-term research.Disclosure of InterestNone declared

Efeito de drogas sintéticas inibidoras do fator de necrose tumoral alfa na artrite reumatoide em ratos

“…As DMARDs atenuam sintomas clínicos e retardam a lesão articular em pacientes com AR (THOMPSON, et al, 2016;AGARWAL, 2011 (ATZENI et al, 2015;ATZENI et al, 2013;RAMIRO et al, 2014) e infecções oportunistas graves (ATZENI et al, 2015;CURTIS et al, 2011;BONGARTZ et al, 2006) em comparação com as tradicionais DMARDs utilizadas no tratamento da AR CURTIS et al, 2011;CURTIS et al, 2010;ASKLING et al, 2007), além de maior risco de ocorrência de neoplasias malignas (BONGARTZ et al, 2006). (SCOVILLE, 2001;KEESAL et al, 1999;SCOVILLE e READING, 1999;LEE et al, 1997;GUTIÉRREZ-RODRÍGUEZ et al, 1989; GUTIÉRREZ-RODRÍGUEZ, 1984) e outros 6 estudos clínicos com a PTX, sendo dois deles nos últimos 4 anos (BUBLIKOV et al, 2016;MOHAMMED et al, 2013;USHA et al, 2002;DUBOST et al, 1997;ISHII et al, 1997;MAKSYMOWYCH et al, 1995). A PTX (C 13 H 18 N 4 O 3 ), nomenclatura oficial IUPAC: 3,7-dimetil-1-(5oxohexil)purina-2,6-dione (National Center for Biotechnology Information, 2017a), parece suprimir a produção de TNF-α bloqueando a transcrição do gene desta citocina em macrófagos e leucócitos murinos e humanos (NEVES et al, 2015;ZHANG et al, 2010;KRETH et al, 2010;WEINBERG et al,1992;HAN et al,1991;THIEL et al,1991), além de aumentar os níveis intracelulares de adenosina 3',5'-monofosfato cíclico (AMPc) em macrófagos de ratos, inibindo a produção de TNF-α por essas células (CORRÊA, 2008;SZTRYMF et al, 2004).…”

“…A PTX tem mostrado eficácia sobre a artrite experimental em ratos (PAL et al, 2016b;MOHAMED et al, 2014;QUEIROZ-JUNIOR et al, 2013;SILVA et al, 2000) e camundongos (TISSI et al, 1999). Os estudos da PTX no tratamento de pacientes AR (BUBLIKOV et al, 2016;MOHAMMED et al, 2013;USHA et al, 2002;ISHII et al, 1997;MAKSYMOWYCH et al, 1995) sugerem um potencial efeito antirreumático (ISHII et al, 1997;USHA et al, 2002). Dentre as drogas propostas no presente estudo, até o momento a PTX é a que foi avaliada em maior número de pacientes (244) em estudos clínicos (BUBLIKOV et al, 2016;MOHAMMED et al, 2013;USHA et al, 2002;DUBOST et al, 1997;ISHII et al, 1997;MAKSYMOWYCH et al, 1995), nenhum desses estudos efetivamente conclusivo em recomendar o uso da PTX no tratamento da AR.…”

“…No contexto dos efeitos adversos dessas drogas, não há menção de algum para a PTX nos relatos disponíveis sobre seu emprego no tratamento na AR em modelos experimentais (PAL et al, 2016b;MOHAMED et al, 2014;QUEIROZ-JUNIOR et al, 2013;VALE et al, 2004;ABDEL-SALAM et al, 2003;SILVA et al, 2000;TISSI et al, 1999;SINGH et al, 1997) e clínicos (BUBLIKOV et al, 2016;MOHAMMED et al, 2013;USHA et al, 2002;DUBOST et al, 1997;ISHII et al, 1997;MAKSYMOWYCH et al, 1995). Quanto ao uso do ROL no tratamento da AR, os raros estudos se restringem a modelos experimentais em ratos e camundongos (PAL et al, 2016a;THABET et al, 2016;JIANG et al, 2015;KORHONEN et al, 2013;MCCANN et al, 2010;YAMAKI et al, 2007;YAMAKI et al, 2004;FRANCISCHI et al, 2000;LAEMONT et al, 1999;NYMAM et al, 1997;ROSS et al, 1997;SINGH et al, 1997;SEKUT et al, 1995) BRZUSTEWICZ e BRYL, 2015).…”

“…Pentoxifilina (PTX), rolipram (ROL), rupatadina (RUP) e talidomida (TAL) são fármacos sintéticos de baixo custo, já exaustivamente avaliados clinicamente, classicamente utilizados na terapêutica de outras doenças, potencialmente inibidores da produção de TNF-α e/ou de fatores relacionados e, com exceção da RUP, já parcialmente avaliados, em maior ou menor grau, quanto ao potencial antiartrítico (PAL et al, 2016a;PAL et al, 2016b;THABET et al, 2016;JIANG et al, 2015;KORHONEN et al, 2013;BUBLIKOV et al, 2016;MOHAMMED et al, 2013;MCCANN et al, 2010;YAMAKI et al, 2007;YAMAKI et al, 2004;USHA et al, 2002;SCOVILLE, 2001;FRANCISCHI et al, 2000;KEESAL et al, 1999;LAEMONT et al, 1999;SCOVILLE e READING, 1999;DUBOST et al, 1997;ISHII et al, 1997;LEE et al, 1997;NYMAM et al, 1997;ROSS et al, 1997;SINGH et al, 1997;MAKSYMOWYCH et al, 1995;SEKUT et al, 1995;GUTIÉRREZ-RODRÍGUEZ et al, 1989;GUTIÉRREZ-RODRÍGUEZ, 1984 (HUIZINGA et al, 1996). Por sua vez, apenas ROL e TAL já foram avaliadas individualmente em modelo experimental CIA, não havendo dados prévios sobre quantificação de aminopeptidase básica (APB), bem como de alaninatransaminase (ALT), aspartato-transaminase (AST) e densitometria óssea sob tratamento com PTX, ROL, RUP e TAL.…”