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ID PMID Title PublicationDate abstract
19027090 Anti-TNFalpha therapy in a cohort of rheumatoid arthritis patients: clinical outcomes. 2009 Jan OBJECTIVE: To assess the effectiveness of anti-TNFalpha agents by analysing the principal clinical outcomes in patients with active rheumatoid arthritis (RA). METHODS: 1010 patients who received no clinical benefit from previous treatment with methotrexate and/or other DMARDs, were subsequently treated with one or more of the anti-TNFalpha agents. RESULTS: After the first six months of anti-TNFalpha therapy, 29% of the patients showed a good and 47% a moderate European League Against Rheumatism (EULAR) response, and this positive result was maintained after two years of follow-up. Their median Disease Activity Score based on the erythrocyte sedimentation rate and the evaluation of 28 joints (DAS28) decreased from 5.94 at baseline to 4 after six months (p<0.001; Delta 1.94), and further significant responses were also observed after 12, 18 and 24 months; their median 36-month DAS28 score reflected mild disease activity. The median Health Assessment Questionnaire (HAQ) score fell from 1.34 at baseline to 1 after six months of therapy (Delta 0.34; p<0.05), and a further significant reduction was observed during the second and third year of follow up. CONCLUSIONS: Especially when combined with DMARDs, anti-TNFalpha drugs can induce a good clinical response regardless of the particular molecule used, whereas their combination with steroids does not seem to improve disease outcomes at any time during follow-up.
19234364 The efficacy and mechanism action of RvCSd, a new herbal agent, on immune suppression and 2009 Feb The aim of the present study is to investigate the potential therapeutic action of RvCSd, an oriental herbal mixture, in an experimental model of rheumatoid arthritis (RA). DBA/1J mice were immunized with type II collagen. After a second collagen immunization, mice were treated with RvCSd or methotrexate (MTX) orally once a day for 35 days, and the incidence, clinical score, and joint histopathology were evaluated. The inflammatory response cytokines and cartilage protection effect were determined by measuring the levels in the joints and sera. The Th1/Th2-mediated auto-reactive response was evaluated by determining the proliferative response and cytokines of drained spleen cells stimulated with type II collagen. RvCSd treatment significantly reduced the incidence and severity of CIA, markedly abrogating joint swelling, synovial hyperplasia, and cartilage destruction. RvCSd significantly inhibited the production of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6, IL-2, interferon (IFN)-gamma, and matrix metalloproteinases (MMP)-1 and up-regulated anti-inflammatory cytokines IL-4, IL-10, and metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, RvCSd has therapeutic effects exerted through inhibition of inflammatory and Th1 responses, regulation of MMP/TIMP, and induction of regulatory T cells in CIA; these effects make RvCSd an outstanding candidate for use as an immune suppressive and cartilage protective medicine in RA patients.
19326186 Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a redu 2009 The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-alpha used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4-8, 12-16, and 20-24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12-16 and 20-24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12-16 and in five patients (50%) at weeks 20-24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics.
19012363 Cost-effectiveness of sequential therapy with tumor necrosis factor antagonists in early r 2009 Jan OBJECTIVE: To estimate the comparative lifetime cost-effectiveness of sequenced therapy with tumor necrosis factor (TNF) antagonists as the initial therapeutic intervention for patients with early rheumatoid arthritis (RA). METHODS: Because patients with RA switch regimens many times throughout the course of disease, sequenced therapeutic interventions were modeled, continuing until the last effective agent failed or death occurred. The model used published clinical outcomes from short-term, randomized controlled trials. Direct treatment costs and costs of lost productivity were modeled for each of 5 alternative treatment sequences. Incremental cost-effectiveness ratios are expressed as quality-adjusted lifeyears (QALY) gained. RESULTS: Treatment sequences that included TNF antagonists produced a greater number of QALY than conventional disease modifying antirheumatic drug regimens alone. The cost-effectiveness of sequenced therapy initiated with adalimumab plus methotrexate (MTX) extendedly dominated both infliximab-plus-MTX-initiated and etanercept sequences. The cost of adalimumab plus MTX per QALY was US $47,157 excluding productivity losses, and $19,663 including productivity losses. A supplementary sequence that incorporated adalimumab-plus-MTX-initiated first-line therapy followed by another TNF antagonist as second-line therapy was modeled; this sequence resulted in additional QALY gained and extendedly dominated all single-TNF strategies. CONCLUSION: Of the 3 single-TNF antagonist sequences, the adalimumab-plus-MTX-initiated sequence was cost-effective in producing the greatest number of QALY. Multiple TNF strategies, such as the supplementary sequence modeled in this analysis, may be cost-effective in producing even greater health gain.
19604445 Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no association with re 2009 May OBJECTIVE: MTHFR is an enzyme involved in the folate pathway. It has been suggested that common polymorphisms in its gene (C677T and A1298C) could be related to different methotrexate (MTX) response and toxicity in rheumatoid arthritis (RA) patients. Agreement has not been found yet and there is no data on rheumatic Italian patients. The aim of this study is to determine if a genetic screening can help in planning the treatment in these patients. METHODS: We enrolled 84 Northern Italian patients affected by RA (n=79), psoriatic arthritis (n=4) and ankylosing spondylitis (n=1), who received MTX. Subjects who achieved at least ACR20 response in 6 months and maintained it during the following 6 months were defined as "responders"; those who did not obtain a disease control after 6 months of MTX were classified as "non responders". Patients who experienced MTX adverse events were defined "with toxicity", those who did not, as "without toxicity". Genotypes were determined by polymerase chain reaction. RESULTS: Genotype frequency was consistent with that reported in a healthy population from Italy. We did not find any statistically significant difference in genotype/allele distribution between the groups. In patients receiving folic acid supplementation MTX toxicity was recorded only in 18 cases (24%), while all the 8 patients not receiving it experienced MTX adverse events (p=0.00). CONCLUSION: In our study we did not find any association between MTHFR genotype/allele and MTX response or toxicity. At the moment there is not sufficient evidence for MTHFR screening in patients who are candidate for MTX.
21085019 Observational cross-sectional study revealing less aggressive treatment in Japanese elderl 2010 Dec BACKGROUND: Elderly patients with rheumatoid arthritis (RA) have more aging-related complications than nonelderly patients with RA. OBJECTIVES: The objective of the study was to investigate the treatment status of elderly patients with RA. METHODS: Between January and March 2008, 969 patients with RA were enrolled in this observational cross-sectional study. Prescription of disease-modifying antirheumatic drugs (DMARDs) and corticosteroids and laboratory data related to RA, including matrix metalloproteinase 3, rheumatoid factor, and anti-cyclic citrullinated peptide antibody levels, were compared between the elderly and the nonelderly patients. RESULTS: Fewer DMARDs were prescribed to the elderly patients (1.40 [SD, 0.57] vs. 1.51 [SD, 0.61]; P = 0.029). Furthermore, a lower percentage of patients received methotrexate (MTX) (47.2% vs. 56.9%; P = 0.0001), a lower average dosage of MTX was administered (5.46 [SD, 1.66] mg/wk vs. 5.96 [SD, 1.77] mg/wk; P = 0.0001), and fewer biologic DMARDs were used (1.46% vs. 5.59% for infliximab, P = 0.0008; 0.58% vs. 3.19% for etanercept, P = 0.0038) in the elderly group. The laboratory data suggested that the disease status was uncontrolled to a greater extent, and complications were more common in the elderly group. CONCLUSION: Elderly patients with RA receive less aggressive treatment than nonelderly patients with RA, despite laboratory evidence for poorly controlled disease status among the elderly. The use of a less aggressive regimen could be attributed to the higher prevalence of complications and problems. Therefore, the elderly with RA should be considered a different patient population from the viewpoint of treatment and be administered specialized medical care.
19066176 Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneou 2009 Jun OBJECTIVE: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. RESULTS: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. CONCLUSION: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.
19665644 Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to m 2009 Aug 8 BACKGROUND: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. METHODS: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration <1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. FINDINGS: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1.59 [95% CI 1.10-2.30], p=0.0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. INTERPRETATION: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. FUNDING: Swedish Rheumatism Association, Schering-Plough.
20149325 Risk and management of liver toxicity during methotrexate treatment in rheumatoid and psor 2009 Nov OBJECTIVES: To systematically review the literature on liver toxicity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients treated with methotrexate (MTX), as an evidence base for generating clinical practice recommendations for the management of MTX and the indication for a liver biopsy (LB) in case of elevated liver enzymes (LE). METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, Cochrane Library and ACR/EULAR meeting abstracts. Data on the incidence of elevated LE, subsequent adjustments in MTX therapy and the prevalence of fibrosis/cirrhosis in pre-MTX and post-MTX LB were pooled. RESULTS: Forty-seven out of 426 identified references were included in the systematic review. For RA, the incidence rate of elevated LE in the first three years of MTX use was 13/100 patient-years with a cumulative incidence of 31%. MTX was permanently discontinued in 7%, paused or reduced in 26% and continued without any adjustment in 67% of patients with an abnormal test. After 4 years of MTX use, LB showed in 15.3% of the (unrelated) cases mild fibrosis, in 1.3% severe fibrosis and in 0.5% cirrhosis, while pre-MTX biopsies showed 9%, 0.3% and 0.3% abnormalities, respectively. For PsA, evidence is limited. Additional studies suggest that cumulative MTX dose and serial LE elevations among other risk factors are related to liver pathology. CONCLUSIONS: This review suggests that LE elevations during MTX therapy are a frequent but transient problem, that serial abnormal LE tests might be associated with liver pathology, but that cirrhosis is relatively rare. It is, however, not clear from the literature how therapy should be adjusted in case of elevated LE and to what extent MTX independently attributes to liver toxicity.
19953907 [Efficacy and safety of infliximab in patients with rheumatoid arthritis]. 2009 Jul 21 OBJECTIVE: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA). METHODS: Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated. RESULTS: After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy. CONCLUSION: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.
19626390 Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately 2009 Clinical squeal of the treatment of rheumatoid arthritis patients with methotrexate (MTX) according to the Japanese government recommended dose of 8 mg/week was evaluated prospectively. A total of 176 patients with active RA attending Konan Kakogawa Hospital and Kobe University Hospital were enrolled. Patients' profile at the start of study was Class 2.0 +/- 1.1 and X-ray stage 2.6 +/- 1.0. The effects of MTX treatment were evaluated by the American College of Rheumatology (ACR) core set, disease activity score of 28 joints (DAS28), and European League Against Rheumatism (EULAR) response criteria. A modified Sharp method was used to evaluate the radiographs. The improvement in the clinical signs and symptoms of the ACR core set was maintained for a 24-month period (p < 0.05). The ACR20/50/70 and DAS28 were also improved at the 12- and 24-month assessments. However, 82 of 130 patients (63.5%) were found to be nonresponders at 24 months of MTX therapy, as evaluated by EULAR response criteria. The X-ray study showed that joint destruction progressed despite the treatment. Thus, long-term MTX treatment performed in accordance with the Japanese 8 mg/week regimen appears to be favorable in terms of the signs and symptoms of RA; however, it is clearly insufficient for and cannot halt the progression of rheumatic joint destruction.
21044436 Long-term safety of methotrexate in the treatment of rheumatoid arthritis. 2010 Sep Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so. The safety profile of MTX has been studied over 25 years with very few clinically important adverse events in the weekly low-doses used for RA treatment. The importance of MTX in earlier and more aggressive management of RA patients cannot be overstated. MTX courses show some of the longest continuation rates reported in clinical medicine, due to both effectiveness and safety. The safety profile of MTX indicates that it is among the safest of any mediation used for the treatment of any arthritis. Better information on the effectiveness and safety of weekly-low dose MTX should be communicated to all health professionals involved in the management of RA patients.
19663190 [Combined basic therapy of rheumatoid arthritis with methotrexate and plaquenil]. 2009 AIM: To compare efficacy of basic RA treatment with methotrexate+plaquenil and basic monotherapy with methotrexate. MATERIAL AND METHODS: Two groups of rheumatoid arthritis (RA) patients were studied: group 1 (n = 82) received combined basic treatment with methotrexate (7.5 mg/week) in combination with plaquenil (0.2 ?mg/day); group 2 (n = 60) received methotrexate monotherapy according to the same scheme; all the patients received also diclofenak in a dose 100 mg/day; low-dose glucocorticosteroids were given to 36 and 24 patients, respectively. To improve methotrexate tolerance, all the patients took folic acid (1-2 mg/day 5 days a week). Efficacy of the treatment was evaluated by regression and final value of inflammation activity. RESULTS: 6-month treatment produced in groups 1 and 2 good effect in 27.6 and 21.4%, satisfactory effect--in 65.5 and 66.6% patients, respectively. No effect was seen in 6.8 and 11.9% patients, respectively. A good effect was achieved in group 1 in 73.3 +/- 5.4 days; in group 2--in 93.7 +/- 5.9 days (p < 0.05). In 12 months good and satisfactory effects persisted. Side effects occurred with the same frequency in both groups primarily in those who did not take folic acid. CONCLUSION: Combined basic therapy of RA with methotrexate and plaquenil was more effective than monotherapy with methotrexate because it produced good effects more frequently and earlier while no response was seen less often.
19539849 Methotrexate-related lymphoproliferative disorder with extensive vascular involvement in a 2009 Jul We describe the development of a cutaneous lymphoproliferative disorder in a patient with rheumatoid arthritis who was treated with methotrexate. Skin manifestations were characterized by thrombophlebitis-like lesions and ulcerated nodules. Histologic examination revealed large polymorphic atypical cells including Reed-Sternberg-like cells expressing CD20 and CD30 in the dermis and subcutaneous tissues. Tumor cells infiltrated the walls of dermal arterioles, subcutaneous arteries, and veins, leading to the destruction of vascular structures. Activation of Epstein-Barr virus was detected. Skin lesions improved remarkably after the discontinuation of methotrexate. This case illustrates the rare occurrence of cutaneous vascular involvement in methotrexate-related lymphoproliferative disorder that did not require any specific chemotherapy.
19015207 Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis 2009 Jun BACKGROUND: Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. OBJECTIVE: To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). METHODS: An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. RESULTS: Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p< or =0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and -0.4, respectively, versus 1.2 for placebo (rank analysis p< or =0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were -0.50 and -0.50, respectively, versus -0.14 for placebo (p< or =0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. CONCLUSION: Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. TRIAL REGISTRATION NUMBER: NCT00175877.
19804686 Rituximab for the treatment of rheumatoid arthritis. 2009 Sep This paper presents a summary of the evidence review group's critical review of the evidence for the clinical effectiveness and cost-effectiveness of rituximab for the treatment of severe rheumatoid arthritis (RA) following failure of previous therapy, including one or more tumour necrosis factor-alpha inhibitors (TNFi), compared with current standards of care, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's clinical evidence came from one randomised, placebo-controlled, double-blind trial (REFLEX--Random Evaluation of Long-term Efficacy of Rituximab in Rheumatoid Arthritis) comparing rituximab plus methotrexate (MTX) with placebo plus MTX in 517 patients with long-standing refractory RA. Rituximab plus MTX was more effective than placebo plus MTX across a range of primary and secondary outcome measures, e.g. American College of Rheumatology (ACR) responses, Health Assessment Questionnaire (HAQ). However, this evidence cannot be used directly to address the manufacturer's analysis of the decision problem because, in the REFLEX trial, rituximab was not compared with a relevant comparator (e.g. leflunomide or second or third TNFi). Long-term efficacy data for retreatment with rituximab are favourable, with an estimated mean time to retreatment of 307 days (n = 164). Evidence from a further five trials is presented as the basis for indirect comparisons with other disease-modifying antirheumatic drugs (DMARDs); however, it is not clear that all relevant clinical studies have been included in the indirect comparison exercise, the rationale for the choice of indirect comparison method adopted is unclear and the indirect comparison method used to adjust the ACR responses only uses a single value for the reference placebo. The submitted microsimulation Markov model was based upon the REFLEX trial. For the 'NICE-recommended' scenario and the 'sequential TNFi' scenario, the original submission reports incremental cost-effectiveness ratios (ICERs) of 14,690 pounds and 11,601 pounds per quality-adjusted life-year (QALY) gained respectively. After model assumptions were adjusted to more realistic estimates by the ERG, the ICERs for the NICE-recommended scenario and the sequential use of TNFi range from 37,002 pounds to 80,198 pounds per QALY gained and from 28,553 pounds to 65,558 pounds per QALY gained respectively. The guidance issued by NICE in August 2007 states that rituximab in combination with methotrexate is recommended as an option for the treatment of adults with severe active rheumatoid arthritis who have had an inadequate response to or intolerance of other DMARDs including treatment with at least one TNFi therapy.
19644623 Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arth 2009 Jul INTRODUCTION: Disease-modifying anti-rheumatic drugs (DMARDs) currently form the mainstay of treatment of rheumatoid arthritis (RA). We aimed to evaluate the retention rates of "therapeutic segments" of DMARDs in patients with RA. METHODS: This was a cross-sectional study of RA patients with at least one year of follow-up. A therapeutic segment is said to begin when one DMARD combination is instituted and it ends with a subsequent change. The disability index for each patient was calculated using a modified health assessment questionnaire. Retention rates were calculated using the Kaplan Meier survival analysis. RESULTS: 375 DMARD courses in 102 patients were analysed. 99 courses were being continued at the time of the study and hence were censored for the purposes of analysis. The respective median (interquartile range [IQR]) retention period for segments containing methotrexate (MTX), sulfasalazine, hydroxychloroquine and leflunomide was 28 (15-45), 12 (3-20), 18 (9-24), 15 (4-32) months. The log-rank statistical test indicated that MTX was retained longer singly (median [IQR] 43 [32-70] months) than in combination (median [IQR] 19 [10-24] months) (p-value is 0.001). The commonest reason for the discontinuation of the DMARD segment was the disease "slipping out" of control (51.1 percent) followed by adverse effects (24.3 percent). Treatment termination on account of disease control was encountered in 16.3 percent of courses only. As many as 63 percent of single DMARD segments were changed because of disease "slip out" as compared to 41 percent of combination DMARD segments. Adverse effects were a more frequent cause of termination of the combination segments (32 vs. 15 percent). CONCLUSION: MTX, used singly, had the highest retention rates among all the DMARDs used in RA patients. Disease "slip out" and adverse effects frequently required a change of the therapeutic segment.
19445880 [Methotrexate-associated lymphoproliferative disorder presenting as oral ulcers in a patie 2009 Mar Methotrexate-associated lymphoproliferative disorders are a heterogeneous group of lymphoid proliferations or lymphomas that develop in patients with autoimmune diseases treated using methotrexate. These lymphoproliferative disorders are often associated with Epstein-Barr virus infection and occasionally regress after the withdrawal of methotrexate therapy. The lymphoproliferative disorder in this case was diffuse large B-cell lymphoma, unusually presenting as oral ulcers in a 79-year-old woman on treatment with methotrexate for longstanding rheumatoid arthritis. Latent membrane protein 1 positivity was detected by immunohistochemistry and Epstein-Barr-virus encoded small RNA positivity by chromogenic in situ hybridization. Clonality was confirmed by immunohistochemistry (kappa light-chain restriction), polymerase chain reaction (monoclonal immunoglobulin H gene rearrangement), and capillary electrophoresis (GeneScan). Staging procedures were negative. Withdrawal of methotrexate therapy led to complete remission within 6 weeks, and the patient is alive and disease-free 18 months after the diagnosis was made. The oral cavity is not often involved in the initial presentation of methotrexate-associated lymphoproliferative disorders, and presentation with intraoral ulcers is very rare. We have performed a review of the literature on methotrexate-associated lymphoproliferative disorders presenting as ulcers in the oral cavity.
21044441 Folate supplementation during methotrexate therapy for rheumatoid arthritis. 2010 Sep Methotrexate (MTX), an antifolate, is an anchor drug for the treatment of rheumatoid arthritis (RA). Both folic acid (FA) and folinic acid (FLN) supplements have been shown to reduce the toxicity of MTX when used in RA therapy. The effect of folate supplementation on MTX efficacy still needs to be studied. FA supplementation has been found to have a beneficial effect on homocysteine (hcy) metabolism and may prevent the formation of the less effective metabolite 7-hydroxy-MTX. The cost of FA supplements is substantially less than the cost of FLN supplements. This article reviews clinical trials related to folate supplementation during MTX therapy for RA.
19626391 Impact of trough serum level on radiographic and clinical response to infliximab plus meth 2009 This study is a prospective, randomized, double-blind study to compare the efficacy and safety of 10 mg/kg infliximab with those of 3 mg/kg infliximab treatment in methotrexate-refractory rheumatoid arthritis patients. After the patients received 3 mg/kg infliximab infusion at weeks 0, 2, and 6, they were randomly assigned to be administered 3, 6 or 10 mg/kg infliximab every 8 weeks from week 14 to 46. Mean American College of Rheumatology improvement (ACR-N) at week 54, the primary endpoint, was 51.3% and 58.3% for the 3 mg/kg and 10 mg/kg groups, respectively, with a statistically significant difference. Treatment with 10 mg/kg was found to be remarkably beneficial in patients who had not responded to three infusions with 3 mg/kg at week 10. The median changes in the modified Sharp score were 0.0 in the two groups. There were no significant differences in the incidences of adverse events between the groups. In patients who achieved better clinical response or greater inhibition of progression of joint damage, trough serum infliximab level was significantly higher than in patients who did not. The magnitudes of both efficacies were correlated with the trough serum infliximab level (ClinicalTrials.gov number: NCT00691028).