The Efficacy And Safety Of Methotrexate Plus Thalidomide In The Treatment Of Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease, the most common manifestations of which are symmetric polyarthralgia, joint swelling and dysfunction. The pathological characteristics of RA include chronic synovial inflammation and hyperplasia, pannus formation,in the end bone erosion, cartilage loss and joint destruction. If untreated, it would lead to joint deformity and disability.Current international combination programs are far from perfect, so further investigation is required to establish the most effective regimen and approach of combination therapy.Methotrexate(MTX)is one of the most widely used first choice DMARDs in the treatment of RA. A considerable number of RA patients discontinue MTX treatment because of gastrointestinal toxicity such as nausea and vomiting. Therefore, to alleviate gastrointestinal adverse reactions becomes a key factor for these patients.Thalidomide(THd) has antiinflammatory, immuno-modulatory, and antiangiogenic, sedation and antiemetic effects. The mechanism of that include inhibition of tumor necrosis factor-alpha (TNF-a)), IL, up-regulation the expression of VEGF, inhibition bFGF-induced angiogenesis, activation of frontal sleep center. It is now widely used to relieve postchemotherapy nausea and vomiting of tumor patients. THd has anti-TNF-a effect, MTX plus TNF-a antagonists in RA more effective than the single use of MTX. SO, could THd plus MTX more than MTX Validly. Could THd remission nausea and vomiting that caused by MTX. This study is aimed:(1) to compare the efficacy and safety of methotrexate alone and methotrexate plus thalidomide in the treatment of rheumatoid arthritis.(2)to study whether THd can alleviate the gastrointestinal adverse reactions induced by MTX.(3) To analyze the security of the two sets.MethodsThis was a cross-sectional study conducted over3-month period. A total of50patients with active RA from rheumatology outpatient department of The First Affiliated Hospital of Zhengzhou University. Patients were randomly assigned to receive either single MTX or therapeutic alliance with MTX and THd of25cases. The primary end point was the European League Against Rheumatism (EULAR) response criteria at12weeks, the Disease Activity Score in28points (DAS28), Nausea, vomiting complete remission rate. The secondary end points were Tender joint counts, swollen joint counts, erythrocyte sedimentation rate (ESR), health assessment questionnaire(HAQ), PGA (patients global assessment) improment and nausea, vomiting effective rate,the safety of Methotrexate plus Thalidomide group.Results1. Patients and study courseIn THd plus MTX group,5cases of patients with nausea and vomiting,18cases of patients with nausea and without vomiting; In MTX group,6cases of patients with nausea and vomiting,18cases of patients with nausea and without vomiting. Two cases of the THd plus MTX group exited for adverse drug reaction, one case of MTX group exited for gastrointestinal adverse reactions. In the end,47(94.0%) cases for effectiveness and safety evaluation.2. Efficacy Results(1) At week12, the EULAR moderate response rate of the THd plus MTX group and that of the MTX group were39.1%and37.5%respectively, without significant statistical difference(P>0.05). Low disease activity (DAS28<3.2) rate of the two groups were43.5%and41.7%respectively, with no significant statistical difference (P>0.05).(2) At week12, the improvement in tenderness joint count and HAQ score of the THd plus MTX group was significantly higher than that of the MTX group (P<0.05). The improvement in swollen joint count and VAS of the two groups no significant statistical difference (P>0.05).3. Nausea and vomiting alleviation(l)At week4, the nausea and vomiting effective rate78.3%of the MTX plus THd group was lower than MTX group (79.2%), with no statistical difference (.P>0.05); At week12, The nausea and vomiting effective rate91.3%of the MTX plus THd group was lower than MTX group (91.7%), with no statistical difference (P>0.05)；(2) At week4, the nausea and vomiting complete remission rate of the MTX plus THd group(34.8%)was significantly higher than MTX group(4.2%)(P<0.05); At week12, the nausea and vomiting complete remission rate of the MTX plus THd group(47.8%)was significantly higher than MTX group (8.3%)(P＜O.05);4. SafetyIn the THd plus MTX group, drowsiness6cases (26.1%), weakness4cases(17.4%), In the MTX group, no drowsiness and weakness, the drowsiness and weakness of THd plus MTX group were significantly higher than MTX group(P<0.05).In the THd plus MTX group, dizziness cases3(13.0%), elevated liver enzymes2cases (8.7%), edema of face and lower limbs2cases (8.7%), constipation2cases (8.7%), rash lcase(4.4%), and menstrualdisorder lcase(4.4%), no alopecie, no oral ulcers, no leucopenia.In the MTX group, elevated liver enzymes3cases(12.5%), oral ulcers case2cases(8.3%), rash2cases(8.3%), menstrual disorder2cases(8.3%), alopecie1case(4.2%), constipation lcase(4.2%), leucopenia lcase(4.2%), no dizziness and edma. The dizziness, elevated liver enzymes, constipation, rash, menstrualdisorder, alopecie, oral ulcers, leucopenia of the two group no statistical difference (P>0.05).Conclusion1. There is no significant improvement between combination with THd and MTX with MTX alone for the treatment of RA.2. THd could relieve nausea and vomiting caused by MTX.3. The combination therapy of MTX and THd has more adverse events than MTX alone in the treatment of rheumatoid arthritis.