Months Of Methotrexate Treatment Research Articles

Serum adenosine deaminase in patients with rheumatoid arthritis treated with methotrexate.

Objective:Recently, adenosine deaminase (ADA) is introduced as helpful marker in diagnosis, prognosis, and monitoring of treatment in rheumatoid arthritis (RA). The aim of this study was to determine the efficacy of the serum ADA in diagnosis, prognosis, and monitoring of treatment with methotrexate (MTX) in RA.Methods:This was a self-controlled clinical trial conducted in university hospitals of Isfahan, Iran. The serum level of ADA, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were measured for 70 patients with active RA (Disease Activity Score-28 [DAS28] > 3/2). After three months of MTX treatment and disease remission (DAS28 < 2.6) these markers were measured again. ANCOVA multiregression and paired t-test were used to compare and evaluate the mean level and correlation of ADA, ESR, IgM-RF, and DAS before and after RA remission.Findings:The mean value for ADA activity was significantly higher than the normal one compared with other studies. Significant decreases were seen in values of ADA, ESR, RF, visual analogue scale (VAS), and DAS after remission. Also, the correlation coefficient between the values of ADA with ESR and DAS were statistically significant in baseline. Moreover, the statistically significant correlation between ADA and ESR, VAS, and DAS were seen after remission. No correlation was found in the case of the dosage of MTX with the value of ADA.Conclusion:It was concluded that ADA may be considered useful as a marker in diagnosis, prognosis, and monitoring of treatment with Methotrexate in RA.

Updated JIA Treatment Recommendations

Source: Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011; 63(4): 465– 482; doi: 10.1002/acr.20460Over the past 12 years, treatment options for juvenile idiopathic arthritis (JIA) have increased due to the introduction of a new class of medicines, the biologics such as tumor necrosis factor (TNF) alpha inhibitor. This expansion of JIA therapeutic options has made feasible the first evidence-based treatment recommendations for a pediatric rheumatic disease.1 These guidelines were developed after a systematic review of 221 articles by a large, interdisciplinary team convened by the American College of Rheumatology.Five JIA treatment groups were defined: systemic arthritis patients with active systemic features (ie, fever, rash) but no active arthritis; systemic arthritis patients lacking active systemic features but having active arthritis; patients with no more than four active joints; patients with at least five active joints; and patients with active sacroiliac joint involvement.For each group, stepwise recommendations were made based upon the level of disease activity (low, moderate, or high) and the presence of poor prognostic features. Active joints were defined as joints with swelling or limited range of motion and pain or tenderness. For patients with no more than four active joints of any activity level, intra-articular glucocorticoid injections (IAC) with triamcinolone hexacetonide were recommended as initial treatment. Patients with low activity and no poor prognostic factors can be started on a nonsteroidal anti-inflammatory drug (NSAID), but then should receive IAC if they continue to have activity after two months, while patients with high activity and a poor prognostic feature should be started on methotrexate immediately. Poor prognostic features were defined as radiographic damage (ie, bone erosion), hip or cervical spine arthritis, or ankle or wrist arthritis associated with marked or prolonged elevated inflammatory marker (ie, erythrocyte sedimentation rate, C-reactive protein).For patients with at least five active joints, initial treatment with NSAIDs alone was considered inappropriate beyond two months. Initial treatment with methotrexate was recommended for all high activity patients, and for moderate activity patients who have a poor prognostic feature. Methotrexate was also recommended for low activity patients with a poor prognostic feature following one month of NSAID and for moderate activity patients without features of poor prognosis after one to two months of NSAIDs. If a patient continues to have moderate or high disease activity after three months of methotrexate treatment, the addition of a TNF alpha inhibitor was recommended; this was also recommended for low disease activity patients after six months of methotrexate treatment. Patients who continue to have active disease could be changed to a different TNF alpha inhibitor or switched to abatacept, an anti-T cell agent.Systemic arthritis patients can be treated with NSAIDs alone during their initial evaluation, but those with active fever and physician global assessment of very high disease activity should be treated with systemic glucocorticoids and possibly the biologic anakinra. Methotrexate was considered inappropriate for initial management of these patients, but considered appropriate for systemic patients with active arthritis following no more than one month of NSAIDs.These recommendations are a useful reference for pediatricians, but are not intended to serve as a treatment protocol. Treatment still needs to be individualized based upon specific patient features, and initiated and managed by a physician familiar with treating JIA.

Predictors of response to methotrexate in early DMARD naïve rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial

ObjectiveTo identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA).MethodsIn the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and...

Relapse Rate of Uveitis Post-Methotrexate Treatment in Juvenile Idiopathic Arthritis

To evaluate the efficacy of methotrexate (MTX) and the effect of its withdrawal on relapse rate of uveitis associated with juvenile idiopathic arthritis (JIA). Retrospective case series. Data of 22 pediatric JIA patients who were being treated with MTX for active uveitis were studied retrospectively. Relapse rate after the withdrawal of MTX was established. Anterior chamber (AC) inflammation, topical steroid use during the first year of MTX treatment, and associations of relapses after the withdrawal were evaluated statistically. Duration of MTX treatment and its withdrawal was determined individually in collaboration with a rheumatologist with an intention to continue the treatment for at least 1 year and to withdraw in case of inactivity of uveitis and arthritis. Inactivity of uveitis was defined as the presence of ≤0.5+ cells in the AC. Eighteen patients (18/22; 82%) showed improvement of their uveitis with a significant decrease in activity of AC inflammation after a minimal period of 3 months of MTX treatment. A topical steroid-sparing effect was observed when MTX was administered for a period of 3 to 9 months. MTX was discontinued because of inactive uveitis in 13 patients. In 9 patients (8/13; 69%) a relapse of uveitis was observed after a mean time of 7.5 months (± SD 7.3). Six patients (6/13; 46%) had a relapse within the first year after the withdrawal. Relapse-free survival after withdrawal of MTX was significantly longer in patients who had been treated with MTX for more than 3 years (P = .009), children who were older than 8 years at the moment of withdrawal (P = .003), and patients who had an inactivity of uveitis of longer than 2 years before withdrawal of MTX (P = .033). Longer inactivity under MTX therapy was independently protective for relapses after the withdrawal (hazard ratio = 0.07; 95% confidence interval 0.01-0.86; P = .038), which means that 1-year increase of duration of inactive uveitis before the withdrawal of MTX results in a decrease of hazard for new relapse of 93%. A high number of patients with inactive uveitis relapse quickly after the withdrawal of MTX. Our results suggest that a longer period of inactivity prior to withdrawal and a longer treatment period with MTX reduce the chance of relapse after withdrawal.

Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis

ObjectiveTo examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naïve patients with psoriatic arthritis (PsA).MethodsData on 430 patients with PsA participating in an ongoing longitudinal observational...

Serum Osteopontin as a Predictive Marker of Responsiveness to Methotrexate in Juvenile Idiopathic Arthritis

To evaluate if serum concentrations of osteopontin (OPN) at baseline in patients with juvenile idiopathic arthritis (JIA) represent a potential predictor of responsiveness to methotrexate (MTX). At diagnosis, 60 children with active JIA received MTX in addition to nonsteroidal antiinflammatory drugs. After 12 months of MTX treatment, 30 patients were defined as responders; the 30 nonresponders received anti-tumor necrosis factor-alpha therapy (etanercept) in addition to MTX; this group was then enrolled for an additional 12-month study period. No patient had received steroids within 6 weeks before entering the study. Fifty healthy children matched for sex and age acted as controls. OPN serum levels were measured at baseline, before MTX, and then at 6 and 12 months. In the nonresponder patients, OPN was evaluated again after 6 and 12 months of etanercept treatment. At baseline, OPN values were significantly higher (p = 0.0003) in JIA patients than in controls, with no significant differences among the different JIA subtypes. At baseline, OPN levels were lower in responders than in nonresponder patients (14.16 +/- 10.1 microg/ml vs 33.2 +/- 18.1 microg/ml, respectively). After 12 months of MTX treatment, OPN levels were significantly reduced in comparison to baseline in both responder and nonresponder groups (p = 0.0017, p = 0.0048, respectively). In nonresponders, etanercept significantly reduced OPN levels at 6 and 12-month followup in comparison to baseline (p = 0.002, p = 0.008, respectively). No significant differences were found among OPN levels and disease activity. Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.

IL-1B and IL-1RN Gene Polymorphisms in Rheumatoid Arthritis: Relationship with Protein Plasma Levels and Response to Therapy

To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy. We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR). None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy. The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.

Experience with the use of low-dose methotrexate for inflammatory bowel disease.

Thiopurine drugs (azathioprine and 6-mercaptopurine) are well established in the treatment of patients with inflammatory bowel disease. However, some patients are intolerant or resistant to thiopurine drugs and their management remains a challenge. Several studies have suggested methotrexate is effective for the induction and maintenance of remission in Crohn's disease. This study was conducted because the overall data on clinical efficacy of methotrexate in inflammatory bowel disease remain limited and there are no data regarding fistulating Crohn's disease or concomitant use of methotrexate with thiopurine drugs in inflammatory bowel disease. This study was a retrospective review of medical notes. Clinical response was defined as sustained withdrawal of oral steroids or fistula improvement. New episodes of steroid therapy, infliximab or surgery during the first 6 months were considered as failure to achieve clinical response. Seventy-two patients were studied (66 Crohn's disease and six ulcerative colitis). The mean dose of methotrexate used was 18.2 mg/week. Clinical response was achieved in 22 of 54 patients (40.7%) who completed 6 months of methotrexate treatment. For patients with Crohn's disease, fistula improvement was achieved in eight of 18 (44.4%) patients compared with 11 of 30 (36.7%) receiving methotrexate for steroid withdrawal. Clinical response was achieved in six of 15 patients (40%) treated with methotrexate and azathioprine at the same time compared with 16 of 39 patients (41%) treated with methotrexate alone. Methotrexate is reasonably effective in clinical practice as a steroid sparing agent in inflammatory bowel disease. The efficacy in fistulating Crohn's disease justifies its use as an immunomodulator in these patients. Combined azathioprine and methotrexate treatment appears to offer no advantage over methotrexate alone.