The Value Of Methotrexate Plus Low Dose Glucocorticoid In Rheumatoid Arthritis Individuals’ Target Control

Background and objectivesRheumatoid arthritis(RA) is a systemic autoimmune disease characterized by achronic polyarticular synovial inflammation. Chronic articular inflammation may leadto irreversible joint damage. So, RA has traditionally been associated with asubstantial burden of disease, loss of work productivity and increased mortality. Theprevalence of RA was0．5％-1．0％in the world and0．32％-0．36％in China.Theexact pathogenesis of RA is still unknown to us, It can not be completely cured, butefficiently controlled the disease activity as early as possible is essential to alleviatethe disability and deformity. MTX is considered as the anchor drug among thedisease-modifying antirheumatic agents (DMARDs). MTX is critical in RA, notonly to relieve symptoms of joint pain and swelling but also to protect againstlong-term sequelae such as joint destruction, deformity and disability. And it isinternationally accepted as first choice in the management of RA. MTX plays acentral role when used alone or combined with other DMARDS. But different dosageand mode of administration, the different pharmacokinetics of MTX in differentperson,the individual’s response to treatment is different. There is no exacttherapeutic strategy about MTX in the management of RA to date. Once multinational recommendations for the use of methotrexate in RA point out：Oral methotrexateshould be started at10to15mg/week, with escalation of5mg every2to4weeks upto20to30mg/week, depending on clinical response and tolerability; parenteraladministration should be considered in the case of inadequate clinical response orintolerance.But this recommendation is based on the studies from non–Asian human，can be only used as reference.IF giving patients who still retain midde/high diseaseactivity state after receiving MTX15mg/week treatment for12weeks MTX25mg/week subcutaneous injection,how many patients can achieve remission/lowdisease activity.There is still no conclusion about the question.Our study aims toevaluate the effect of different dosage of MTX on response to RA.MethodMTX-naive patients with a diagnosis of RA according to the2010ACR/EULAR classification criteria were eligible for the study. Patients were prescribedwith15mg/week MTX、5mg/week folic acid and low dose prednisine(≤10mg/d)orally. The activity of disease and adverse drug reaction were collected at4、12week.The Patients who still retain middle/high disease activity state after receivingMTX15mg/week treatment for12weeks were prescribed with MTX25mg/weeksubcutaneous injection. The activity of disease and adverse drug reaction werecollected at week24.The primary assessment criterion was the DAS28-ESR evaluation system.Depending on the primary outcome measure, remission was defined as DAS28-ESR＜2.6, target control was defined as DAS28-ESR score match with remission or lowdisease activity.The secondary assessment criteria were American College ofRheumatology(ARA）、DAS28-based European League against Rheumatism responsecriteria、clinical disease activity index（CDAI）、simple disease activity index（SDAI）.ResultsA total of103patients were enrolled in the trial.94patients were included in theanalysis of clinical efficacy and safety at last. At week4, the frequency of patientswho met DAS28-ESR remission/low disease activity/middle and high disease activity were29.8%/10.6%/59.6%respectively. At week12, the frequency of DAS28-ESRremission/low disease activity/middle and high disease activity were43.6%/13.8%/42.6%respectively. The patients who still retain middle/high diseaseactivity state after receiving MTX15mg/week treatment for12weeks wereprescribed with MTX25mg/week subcutaneous injection,At week24, the frequencyof patients who met DAS28-ESR remission/low disease activity/middle and highdisease activity were15%/17.5%/67.5%respectively.71.3%of the patients with RAwho receiving MTX15mg/week to25mg/week(orally or subcutaneous injection)treatment can meet the standard of target control.The patients who Starting with15mg/week MTX orally, the common adverse drug reactions were gastrointestinalreaction and hepatotoxicity, when MTX is increased to25mg/week,the frequency ofgastrointestinal reaction is decreasing,but the frequency of hepatotoxicity isincreasing. there was not severe adverse reaction during the study.Conclusions1. For the patients with RA who still retain middle/high disease activity stateafter receiving MTX15mg/week plus low dose glucocorticoidtreatment,increasing MTX dosage and changing administration can make apart of the patient meet the standard of target control.2.71.3%of the patients with RA who receiving MTX15mg/week to25mg/week plus low dose glucocorticoid treatment can meet the standard oftarget control.this therapeutic schedule should be recommended in RAtreatment.