Objective To evaluate the efficacy and safety of Leflunomide (LEF) in the treatment of Rheumatoid Arthritis (RA), so as to provide scientific proof for applying LEF in China. Methods Randomized controlled trials (RCTs) about the effect of LEF on patients with RA from January 1989 to January 2011 were searched from the following databases, CNKI, WanFang Data, MEDLINE, EMbase and CBM. After two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted the data and assessed the quality, the data were analyzed by RevMan 5.0 software. Results Among 3247 patients in 16 included RCTs, 1711 patients were in the LEF group, while the other 1536 patients were in the Methotrexate (MXT) group. The results of meta-analyses showed there was no significant difference in the efficacy between LEF and MXT (RR=1.03, 95%CI 0.94 to 1.11, Pgt;0.05), but a significant difference was found in the side reaction (RR=0.67, 95%CI 0.49 to 0.94, Plt;0.05). Conclusion Based on the current studies, Leflunomide is as effective as the commonly-used Methotrexate in the treatment of rheumatiod arthritis at present, much safer than Methotrexate, and thought as a safe and effective SAARD. For the quality restrictions of the included studies, more double blind RCTs with high quality are required to further assess the effects.
Objectives To systematically review the efficacy and safety of certolizumab pegol (CZP) plus methotrexate (MTX) for active rheumatoid arthritis. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) on CZP plus MTX vs. MTX plus placebo for active rheumatoid arthritis from inception to May, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, data were analyzed by using Stata 11.0 software. Results Seven RCTs were included. The results of meta-analysis showed the CZP plus MTX group was superior to MTX plus placebo group in ACR20 (CZP400 mg: RR=2.86, 95%CI 1.70 to 4.79, P<0.001; CZP200 mg: RR=3.76, 95%CI 2.59, 5.46, P<0.001), ACR50 (CZP400 mg: RR=3.91, 95%CI 2.10 to 7.27, P<0.001; CZP200 mg: RR=4.86, 95%CI 3.20 to 7.39, P<0.001), and ACR70 (CZP400 mg: RR=5.65, 95%CI 1.99 to 16.06, P=0.001; CZP200 mg: RR=10.08, 95%CI 5.11 to 19.89, P<0.001). The CZP plus MTX group was also superior to MTX plus placebo group in swollen joint counts (SMD=–12.72, 95%CI –15.39 to –10.06,P<0.001), tender joint counts (SMD=–11.54, 95%CI –13.97 to –9.11,P<0.001), doctor's global assessment of disease activity (SMD=–11.78, 95%CI –13.81 to –9.75,P<0.001), patient's global assessment of disease activity (SMD=–9.62, 95%CI –11.09 to –8.15,P<0.001), and patient's assessment of pain (SMD=–9.10, 95%CI –10.91 to –7.30,P<0.001) and HAQ (SMD=–7.74, 95%CI –8.99, –6.49,P<0.001), respectively. However, the incidence of adverse events in CZP plus MTX group was higher than that in MTX plus placebo group. Conclusions CZP plus MTX is superior to MTX plus placebo for treatment of active rheumatoid arthritis but with higher adverse events. Due to limited quantity and quality of the included studies, the above conclusions are still needed to be verified by more high-quality studies.
ObjectiveTo compare the cost-effectiveness of etanercept combined with methotrexate to methotrexate plus placebo in the treatment of rheumatoid arthritis and to provide references for clinical practice.MethodsDecision tree model was developed to estimate the cost-effectiveness from the perspective of the health care system by TreeAge Pro 2016 software. The cost-effectiveness of the two treatments were compared by incremental analysis, and the robustness of the results were analyzed by sensitivity analysis.ResultsThe cost of etanercept combined methotrexate group in one year duration was ¥212 692, the effective rate (ACR50) was 66.4%; the cost of methotrexate combined with placebo group in one year duration was ¥572, the effective rate (ACR50) was 40.6%. The incremental cost-effectiveness ratio of two groups was ¥818 000/person, and the sensitivity analysis showed that the results were robust.ConclusionEtanercept combined methotrexate is significant more effective than methotrexat. But the cost of etanercept combined methotrexate is too high to afford and is not economical compared to methotrexate.
ObjectiveTo evaluate the safety and efficacy of the intravitreal methotrexate treatment in patients with primary vitreoretinal lymphoma (PVRL). MethodsRetrospective non-comparative interventional case series. Fourteen patients (26 eyes) with biopsy-proven PVRL were included in the study. All patients received examination of Snellen chart visual acuity, fundus color photography and optical coherence tomography (OCT). Among the 24 eyes with recordable visual acuity, 17 eyes has initial visual acuity≥0.1 (0.45±0.20) and 7 eyes with initial visual acuity ranged from light perception to hand movement. The vitreous opacities and (or) subretinal yellowish-white lesions and retinal pigment epitheliumuplift were observed in all eyes. All eyes were treated with intravitreal methotrexate (4000 μg/ml, 0.1 ml) injections according to a induction-consolidation-maintenance regimen. For 26 treated eyes, each received an average of (11.5±6.3) injections. Twenty eyes had finished theintraocular chemotherapy, while 6 eyes had not. Eight of 20 eyes were clinically confirmed free of tumor cells by diagnostic vitrectomy, 12 eyes were still with tumor cell involvement.The follow-up was ranged from 2 to 48 months, the mean time was 18 months. The examination of BCVA, fundus color photography and OCT were performed. No tumor cell was defined as clinical remission. Visual acuity was scored as improved or declined obviously (improved or declined 2 lines) or mild improved or declined (changed within 2 lines). ResultsTwenty eyes achieved clinical remission after (3.5±3.6) injections, 12 eyes of 20 eyes with tumor cell involvement before chemotherapy achieved clinical remission after (5.8±3.0) injections. The mean visual acuity of seventeen eyes with initial visual acuity 0.1 in induction phase and at the end of treatment were 0.36±0.23 and 0.56±0.20, respectively. Compared with before treatment, the visual acuity was mild declined in induction phase (t=1.541, P>0.05), but mild improved at the end of treatment (t=2.639, P<0.05). The visual acuity at the end of treatment in 7 eyes with initial visual acuity<0.1 was ranged from no light perception to 0.1. Of 14 patients, 2 patients have been fatal because of brain lesions progression at 42 and 48 months after diagnosis of primary central nervous system lymphoma. No ocular recurrence was noted during the follow-up in 20 eyes who finished intraocular chemotherapy. ConclusionsPVRL patients can achieve clinical remission after (3.5±3.6) injections by intravitreal chemotherapy of methotrexate, and the visual acuity improved mildly. No ocular recurrence was found during follow-up.
ObjectiveTo evaluate the effect of time-related administration of methotrexate (MTX) on neural cell apoptosis in rats after spinal cord injury (SCI) so as to investigate its potential neuroprotective mechanism and appropriate administration time. MethodA total of 120 male Sprague Dawley rats, 247-286 g in weight, were randomly divided into 4 groups (n=30) :sham group (group A), control group (group B), MTX treating group (group C), and MTX prophylaxis group (group D). The SCI model was established in the rats of groups B, C, and D by improved Allen method, and just laminectomy was performed in group A. MTX (0.5 mg/kg) was administered with tail vein injection at 1, 6, 12, 18, and 24 hours after injury in group C, and at 30 minutes before injury and at 6, 12, 18, and 24 hours after injury in group D; the equivalence saline was injected at 1, 6, 12, 18, and 24 hours after injury in groups A and B. Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neural function at 1, 3, 7, 14, and 21 days after injury, HE staining to observe histological changes, immunohistochemical staining and TUNEL method to measure the expression of Caspase-3 and neural cells apoptosis, respectively. ResultsTen rats died during the experiment in groups B, C, and D; 25 rats in each group were included into the experiments at last. BBB score of group A was significantly higher than that of groups B, C, and D at all time points after injury (P<0.05) . BBB score of groups C and D were significantly higher than that of group B at 3, 7, 14, and 21 days (P<0.05) , and BBB score of group D was significantly higher than that of group C at 3, 7, and 14 days (P<0.05) . The histological observation showed normal structure of spinal cord at all time points after injury in group A. While the degree of SCI in group D was lighter than that in groups B and C, and group C was lighter than group B. At 14 days after injury, the degree of SCI in groups B, C, and D tend to keep the same. The number of Caspase-3 and TUNEL positive cells of groups B, C, and D was significantly more than that of group A at all time points after injury (P<0.05) , group B was significantly more than groups C and D (P<0.05) . The number of Caspase-3 positive cells of group C was significantly more than that of group D at 3, 7, and 14 days (P<0.05) . While the number of TUNEL positive cells of group C was significantly more than that of group D at 3 and 7 days (P<0.05) . And the number of Caspase-3 positive cells and TUNEL positive cells was positively correlated in groups B, C, and D (P<0.05) at 1, 3, 7, 14, and 21 days after injury. ConclusionsLow-dose MTX may effectively reduce the degree of the secondary injury of spinal cord by reducing the nerve cell apoptosis. Better effect can be obtained when MTX is used as prevent method than as a way of treatment.
We reported one case of MTX-induced aplastic anemia and reviewed related literature to investigate the mechanism of action of MTX, and summarize the clinical feature, diagnostic criteria, risk factor, and interventions. These were hoped to arouse the attention of clinicians and clinical pharmacists, in order to effectively prevent, diagnose, and treat MTX-induced aplastic anemia.
ObjectivesTo analyze patients’ values and preferences on individualized medication of high-dose methotrexate so as to support the development of the practice guideline for clinical medication of high-dose methotrexate.MethodsA multicenter cross-sectional study involving patients with osteosarcoma or hematological malignancy in 7 hospitals was conducted by questionnaires to evaluate the perception and willingness on detection of gene polymorphisms (MTHFR C677T, MTHFR A1298C, ABCB1 C3435T and RFC1 G80A) related to methotrexate (MTX) and therapeutic drug monitoring (TDM) of MTX. SPSS24.0 software was used to analyze the data.ResultsA total of 124 patients were involved, including 40 (32.26%) with osteosarcoma and 84 (67.74%) with hematological malignancy. 106 (85.48%) and 117 (94.35%) patients agreed on detection of gene polymorphisms and TDM, respectively. There was a significant difference on preference towards TDM between patients with risk factors for MTX and patients in which risk factors for MTX were not discovered (76.19% vs. 95.08%, P=0.003). The ranking of factors that contributed to the two decision-making was consistent (P<0.01), and specific orders of factors were identical. The clinical efficacy was the primary factor (mean rank 3.45 for detection of genetic polymorphisms and 3.52 for TDM), followed by safety (mean rank 3.01 and 3.16, respectively) and comfort (mean rank 1.73 and 1.79, respectively). Cost (mean rank 1.39 and 1.31, respectively) was the least important factor.ConclusionsThe preferences of patients toward detection of gene polymorphisms and TDM were generally similar, with well acceptance. No significant differences were found on the preferences toward detection of gene polymorphisms. However, patients with or without risk factors for MTX may differ significantly when making decisions on TDM, which may impact on clinical decision-making of clinicians and clinical pharmacists. The perception and willingness of patients should be considered adequately during the development of clinical practice guidelines and clinical practice.
Objective To investigate the effectiveness, safety and cost-effectiveness of leflunomide for rheumatoid arthritis, and formulate an evidence-based treatment plan for a patient with rheumatoid arthritis. Methods We searched the ACP Journal Club, The Cochrane Library (Issue 2, 2007) and MEDLINE (1990 to 2007), and critically appraised the available evidence. Results The available Level A (high quality) evidence showed that the efficacy and adverse events of leflunomide were comparable to those of methotrexate. The total cost of treating patients with leflunomide was significantly higher when compared to methotrexate. The combination of leflunomide and methotrexate in patients with active rheumatoid arthritis unresponsive to methotrexate monotherapy was less costly and more effective than the strategy excluding leflunomide. Given the current evidence, together with our clinical experience and the patient’s preference, methotrexate was administered to the patient. There was an inadequate response after 6 months of treatment. And then, adding leflunomide to methotrexate attained a remarkable response 3 months later. The patient is still being followed up. Conclusion treatment with leflunomide and methotrexate in RA patients can improve the clinical outcomes. Long-term efficacy and toxicity remain to be established.