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ID PMID Title PublicationDate abstract
17469100 The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma 2007 May OBJECTIVE: To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup. METHODS: Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates. RESULTS: Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma. CONCLUSION: In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.
18412314 Low-dose prednisolone in rheumatoid arthritis: adverse effects of various disease modifyin 2008 Jun OBJECTIVE: To assess the incidence and severity of disease modifying antirheumatic drug (DMARD)-induced adverse effects (AE) in patients with rheumatoid arthritis (RA) taking/not taking glucocorticoids (GC). More specifically, we tested whether GC can prolong the survival time of DMARD in patients receiving combination therapy. METHODS: In a retrospective study of 154 patients with RA, data were examined for DMARD therapy and duration of low-dose GC ((3/4) 7.5 mg prednisone equivalent/day). Patients were followed for 2-62 months, and AE were graded following WHO criteria. RESULTS: GC therapy significantly increased the duration of therapy with sulfasalazine (SSZ) from 10.4 +/- 2.3 to 22.5 +/- 1.9 months and for methotrexate (MTX) from 21.8 +/- 2.9 to 43.3 +/- 2.7 months. Stratifying the withdrawal of DMARD for occurrence of AE and loss of efficacy revealed that GC comedication significantly increased the time until AE for users of MTX (3.0 +/- 0.6 vs 18.8 +/- 1.3 mo; p < 0.05), hydroxychloroquine (HCQ; 34.5 +/- 4.6 vs 54.4 +/- 5.1 mo; p < 0.05), and gold (6.6 +/- 0.9 vs 10.5 +/- 0.9 mo; p < 0.05). In patients taking SSZ the time until cessation due to loss of efficacy increased significantly under GC comedication (16.8 +/- 1.2 vs 31.3 +/- 2.9 mo; p < 0.05). However, in patients taking azathioprine (AZA) the duration of therapy decreased from 44.4 +/- 2.6 to 22.3 +/- 1.6 months under GC due to both time until AE and loss of efficacy. Patients under comedication of MTX + GC, HCQ + GC, and AZA + GC experienced significantly more AE compared to the respective DMARD monotherapy. A highly significant reduction was observed in the frequency of erosive RA in patients with GC comedication (n = 30; 49.1%) compared to patients without low-dose GC (n = 81, 80.4%; OR 4.05, 95% CI 1.91-8.66, p < 0.0001). CONCLUSION: Low-dose GC retard radiological progression of RA and exhibit a differential effect on survival of DMARD and degree of AE due to DMARD. Further studies are warranted to address safety and interactions of chronic low-dose GC in RA patients treated with DMARD.
16906380 Infectious myositis involving the piriformis in a patient with rheumatoid arthritis. 2006 A 49-year-old Japanese woman treated with oral corticosteroids, methotrexate, and infliximab for malignant rheumatoid arthritis was admitted because of fever and low back pain. The white blood cell count and C-reactive protein concentration were elevated. Lumbar and pelvic computed tomography showed enlargement of the piriformis muscle including a hypodense area consistent with gas formation. The patient was treated successfully for infectious myositis with intravenous antibiotics.
18975321 Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. 2008 Nov OBJECTIVE: There is evidence supporting a therapeutic range for methotrexate polyglutamate (MTXGlu) concentrations in the treatment of rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of MTXGlu1-5 is required for optimal timing of blood sampling. The aim of this study was to determine the time to steady state and the half-life of accumulation of red blood cell (RBC) MTXGlu1-5 in patients with RA commencing oral MTX, and the time for RBC MTXGlu1-5 to become undetectable and the half-life of elimination of RBC MTXGlu1-5 in patients ceasing treatment with oral MTX. METHODS: Ten patients beginning treatment and 10 patients stopping treatment with low-dose oral MTX were recruited. Blood samples were initially collected weekly, with gradual extension to monthly collection over the study period. RBC MTXGlu1-5 concentrations were assayed by high-performance liquid chromatography. Results were analyzed using a first-order exponential method. RESULTS: The median times to reach steady state in RBCs (defined as 90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of accumulation for RBC MTXGlu1-5 ranged from 1.9 weeks to 45.2 weeks. The median times for MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4 weeks, respectively, for MTXGlu1, MTXGlu2, MTXGlu3, MTXGlu4, and MTXGlu5. The median half-life of elimination for RBC MTXGlu1-5 ranged from 1.2 weeks to 4.3 weeks. CONCLUSION: There is wide interpatient variability of RBC MTXGlu1-5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu1-5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.
17478472 The efficacy of inhibiting tumour necrosis factor alpha and interleukin 1 in patients with 2007 Jul OBJECTIVE: New treatments that inhibit the cytokines tumour necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1) in the treatment of rheumatoid arthritis have proven clinical effect against placebo and methotrexate (MTX) in several clinical trials in early and late-stage disease and different severity groups. Since there are no head-to-head randomized controlled trials directly comparing the currently available treatments, etanercept, adalimumab, infliximab or anakinra, we perform a meta-analysis that adjusts for differences between study characteristics, and allows indirect comparisons between treatments. METHODS: Thirteen trials of cytokine antagonists were included from a systematic review of the literature. They reported the primary outcome of American College of Rheumatology (ACR) response criteria at 6 months or beyond. Meta-analytical methods are used to quantify relative treatment effects, using the log odds ratio of an ACR20 or ACR50 response at 6 months, whilst adjusting for study-level variables. RESULTS: In each of the trials, cytokine treatment was efficacious in comparison with placebo or MTX. For each treatment, the inclusion of MTX in combination improved the response. After adjustment for study-level variables, we found TNFalpha antagonists to be more efficacious compared with anakinra (P < 0.05). Indirect comparisons between the three TNFalpha antagonists indicated no difference in efficacy. Sensitivity analysis using a different statistical model structure confirmed these results. CONCLUSION: When the outcome of interest is the probability of an ACR20 or ACR50 response at 6 months we found: (i) treatment with the IL-1 antagonist anakinra is better than placebo; (ii) for each treatment, the use of combination MTX improves the probability of response; (iii) treatment with any of the TNFalpha antagonists is better than with the IL-1 antagonist anakinra; and (iv) all drugs in the TNFalpha antagonist class are no different from each other.
16385520 The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination t 2006 Jan OBJECTIVE: To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. METHODS: This was a 2-year, multicenter, double-blind, active comparator-controlled study of 799 RA patients with active disease of < 3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co-primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score. RESULTS: Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P < or = 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28-joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups. CONCLUSION: In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.
17037405 [Gastropleural fistula due to perforated gastric ulcer]. 2006 Sep A 65-year-old woman, who had been taking non-steroidal anti-inflammatory drugs (NSAIDs), prednisolone and methotrexate for rheumatiod arthritis, was admitted to our hospital with a sudden onset of left-back and chest pain and breathlessness. A chest radiograph and computed tomography revealed a left-side pneumothorax and pleural effusion. Chest tube was inserted for drainage and the fluid was formed to contain food residuum. Contrast radiography demonstrated escape of soluble contrast medium into the left pleural space. A thoracotomy and transdiaphragmatic revealed a gastropleural fistula. It was repaired and the gastric origin was resected. Pathologic evaluation revealed evidence of chronic peptic ulceration, but no malignant change. Gastropleural fistula due to peptic ulcer without esophageal herniation, malignancy, or traumatic injury is extremely unusual. The cause of the focal adhesion of the gastric ulcer and diaphragm, fistula formation was not certain but was probably related to the ingestion of NSAIDs in combination with prednisolone and other immunosuppressive agents. Although gastropleural fistula is rare, the prognosis in such patients related to early diagnosis and surgical intervention, emphasizing the importance of including this condition when making a differential diagnosis.
16583466 A phase I study assessing the safety, clinical response, and pharmacokinetics of an experi 2006 May OBJECTIVE: To assess safety, clinical response, and pharmacokinetics of subcutaneous (SC) and intramuscular (IM) doses of an experimental formulation of infliximab [including experimental SC doses following administration of commercially-formulated intravenous (IV) infliximab] in patients with rheumatoid arthritis (RA) refractory to methotrexate. METHODS: In this randomized, open-label, 3-stage design, 43 subjects were enrolled in 7 dose groups. In Stage I, 15 subjects received single SC doses of 0.5, 1.5, or 3.0 mg/kg. In Stage II, 21 subjects received one of 3 regimens: 100 mg SC every 2 weeks (3 injections); 3 mg/kg commercially-formulated IV infliximab every 2 weeks (2 infusions) followed by 100 mg SC every 2 weeks (3 injections); or 100 mg IM every 2 weeks (3 injections). In Stage III, 7 subjects received 100 mg SC every 4 weeks (3 injections). RESULTS: No treatment-related serious adverse events were observed, and there were no serious injection site reactions. A low-titer infliximab antibody response was detected in 27% of subjects receiving single SC doses, 5% receiving multiple SC doses, and 43% receiving IM doses. SC administration yielded roughly dose-proportional increases in Cmax and AUC. American College of Rheumatology 20% response (ACR20) was achieved 2 weeks after the last injection by 86.7% of subjects receiving single SC doses, 85.7% receiving SC doses every 2 weeks, 85.7% receiving both IV and SC doses, 57.1% receiving multiple IM doses, and 80.0% receiving SC doses every 4 weeks. CONCLUSION: SC and IM treatment with this experimental infliximab formulation was well tolerated and was associated with a favorable ACR response.
16639484 [A comparison between the Simplified Disease Activity Index (SDAI) and the Disease Activit 2006 Jan OBJECTIVE: To compare the SDAI values to DAS28 scores in RA patients undergoing different DMARD regimens. METHODS: The SDAI is an unweighted numerical sum of five outcome parameters: tender and swollen joint count (based on 28-joint assessment), patient and physician global assessment of disease activity (visual analogue scale: 0-10 cm) and level of C-reactive protein (mg/dl). 80 patients (F/M 68/12; age between 20-68 years, median 52) with active rheumatoid arthritis were prospectively enrolled in the study. The patients were randomly assigned to one of four groups according to the therapeutic regimens: group I: Methotrexate (MTX) 15 mg/weekly + salazopyrin 2 g/daily; group II: MTX 15 mg/weekly + infliximab 3 mg/Kg at time 0, 2, 4 and every 8 weeks; group III: MTX 15 mg/weekly + etanercept 25 mg/twice weekly; group IV: MTX 15 mg/weekly + adalimumab 40 mg/every other week. SDAI and DAS28 were determined at baseline and after 6 months in each patient. Mean changes in SDAI values were compared to those detected in DAS 28 at baseline and after 6 months. RESULTS: SDAI and DAS 28 were found to be significantly correlated at baseline. Moreover, changes in SDAI over time paralleled those in DAS, and were found to be significantly correlated. CONCLUSIONS: SDAI is a valid measure of response to treatment in RA patients undergoing different therapeutic regimens.
18498922 Decreased external home help use with improved clinical status in rheumatoid arthritis: an 2008 Apr OBJECTIVES: The aims of this study were to examine the relationship between external home help (EHH) use (ie, help provided by someone other than family or friends) and clinical response and patient-reported outcomes in patients with rheumatoid arthritis (RA), and to determine whether abatacept treatment in addition to methotrexate reduces the need for EHH. METHODS: EHH use was recorded monthly in the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 12-month, randomized, double-blind, placebo-controlled trial of abatacept in patients with active RA also receiving methotrexate. Clinical response was defined using American College of Rheumatology (ACR) criteria, European League Against Rheumatism (EULAR) criteria, and Disease Activity Scale (DAS)-28 score. Patient-reported outcomes included the Health Assessment Questionnaire (HAQ), 100-mm visual analog scales (VASs) for pain and fatigue, and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) for health-related quality of life. Analysis of covariance and regression analysis were performed to investigate the relationship between change in EHH use and both clinical response and patient-reported outcomes. RESULTS: Of 590 patients enrolled in the study, 232 (39.3%) were receiving EHH at baseline (mean age, 50.2 years; 88% female; 85% white; mean duration of RA, 8.8 years; mean [SD] EHH use, 15.6 [11.3] days). The level of EHH use was consistently higher with poorer scores on the HAQ, pain and fatigue VASs, DAS28, and SF-36. At 12 months, the mean reduction from baseline in EHH use was significantly greater in patients with ACR-50 or ACR-70 clinical response, EULAR good or moderate response, DAS28 remission, and clinically meaningful improvements in patient-reported outcomes. On multiple regression analysis, change in SF-36 Physical Functioning subscale score was the most important contributor to change in EHH after adjustment for other variables. The mean reduction from baseline in EHH use was significantly greater with abatacept compared with placebo over the study period (all, P<0.001). CONCLUSIONS: In this exploratory analysis of data from patients with active RA from the AIM trial, EHH use was decreased significantly with improvements in clinical response, disease activity, and patient-reported outcomes. Treatment with abatacept in addition to methotrexate was associated with significantly decreased EHH use, suggesting that abatacept may have been associated with improved function and increased physical independence in these patients with RA.
18771364 Anti-TNF-alpha immunotherapy is associated with increased gingival inflammation without cl 2008 Sep BACKGROUND: Because periodontitis presents many similarities with rheumatoid arthritis (RA) with regard to tumor necrosis factor-alpha (TNF-alpha)-induced bone resorption, the benefits of TNF-alpha blockade in RA prompted us to determine its efficacy in treating coexisting periodontitis. METHODS: Periodontal status was evaluated in 40 subjects with RA who were divided into two groups: Group I contained 20 subjects who had received infliximab every 6 weeks for > or =22 months at the time of periodontal evaluation. The 20 subjects in group II were evaluated before their first infusion with infliximab. Nine subjects in group II had periodontitis. These subjects were reevaluated after they received nine infusions of infliximab. RESULTS: Infliximab tended to aggravate gingival inflammation as indicated by differences in the modified gingival and papillary bleeding indices between subjects in groups I and II with coexisting periodontitis before and after treatment. Methotrexate had no effect on periodontal status. Although the plaque index revealed that bacterial infection persisted, the probing depth was equal in groups I and II and equivalent before and after treatment in subjects with periodontitis, whereas attachment loss was decreased after infliximab treatment. CONCLUSIONS: Inflammation and destruction constitute two interrelated yet separate components of periodontitis in patients with RA. Therefore, TNF-alpha blockade could be beneficial in the treatment of periodontitis.
18607581 Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of 2008 Nov OBJECTIVE: Methotrexate (MTX) is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 A80G), P-glycoprotein (MDR1 G2677T>A/C and C3435T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TS 2R-->3R), methionine synthase (MS A2756G) and methionine synthase reductase (MTRR A66G) modify MTX transport and metabolic effects and may influence the treatment response. METHODS: A genotyping approach was used to determine the studied polymorphisms in 213 RA patients. RESULTS: We observed that 56 (26.3%) patients discontinued MTX treatment due to poor response and/or toxicity. RFC1 A80G and MDR1 C3435T polymorphisms increased the risk for overall MTX toxicity (P = 0.039, OR = 3.574, 95% CI = 1.065-11.993 and P = 0.032, OR = 7.801, 95% CI = 1.194-50.960 respectively), while MTHFR A1298C polymorphism had a protective effect on overall MTX toxicity (P = 0.027, OR = 0.170, 95% CI = 0.035-0.820). CONCLUSION: Our results suggest that genetic polymorphisms in the folate metabolic pathway and MTX transporters modify the toxicity but not the efficacy of MTX treatment.
18590608 Abatacept in biologic-naïve patients and TNF inadequate responders: clinical data in focu 2008 Aug BACKGROUND: Advances in the understanding of rheumatoid arthritis (RA) immunopathogenesis support the hypothesis for a 'window of opportunity' for therapeutic intervention in RA and the need for rapid and effective treatment strategies, with the ultimate goal of alleviating symptoms and halting progressive joint damage. Biologic therapies targeting pro-inflammatory cytokines have significantly improved the outlook for patients with RA; however, some patients still experience inadequate treatment responses. Recently, therapeutic agents targeting alternative pathways have been developed. One such therapy--abatacept--targets T-cell activation and is approved in the United States for treatment of moderate-to-severe RA and juvenile idiopathic arthritis. OBJECTIVE: To overview the efficacy and safety of abatacept in the treatment of adult patients with active RA and an inadequate response to methotrexate (MTX) or tumor necrosis factor (TNF) antagonists. SEARCH METHODOLOGY: A comprehensive literature search was performed using the National Library of Medicine (MEDLINE), EMBASE and BIOSIS databases (restricted to articles in the English language posted between January 2000 and February 2007). The search terms 'CTLA-4Ig', 'abatacept' and 'ORENCIA' were used, and data from randomized clinical trials were summarized. RESULTS: Abatacept provided clinically meaningful improvements in the signs and symptoms of RA in both MTX and TNF antagonist inadequate responders in Phase II and III studies. Health-related quality of life was also improved with abatacept, which demonstrated an acceptable safety and tolerability profile in both patient populations. Additionally, when assessed in patients with an inadequate response to MTX, abatacept inhibited structural damage progression. CONCLUSION: Although longer-term data are required and differing study designs preclude direct comparisons with other RA therapies, results of clinical trials to date suggest that abatacept has an acceptable safety profile and is an effective treatment option for patients with RA, whether treating biologic-naïve patients or those who have already had an inadequate response to TNF antagonists.
16536638 Long-term experience with etanercept in the treatment of rheumatoid arthritis in elderly a 2006 BACKGROUND: The impact of long-term therapy for rheumatoid arthritis (RA) in elderly (> or = 65 years of age) and younger (< 65 years of age) patients, especially on patient-reported outcomes, has not been well studied. We evaluated patient-reported outcomes in elderly patients treated with etanercept, in contrast to outcomes in younger patients, using data from multiple controlled and open-label extension studies of patients with early RA (ERA; < or = 3 years) and late RA (LRA; disease-modifying antirheumatic drug [DMARD]-refractory RA). METHODS: This post hoc analysis included adult patients with RA enrolled in controlled, double-blind studies (up to 2 years) and subsequent open-label extension studies (up to 4 years). Patients were evaluated according to age at baseline of the original study. Patients may have received etanercept, placebo or methotrexate during the blinded treatment phases, but all patients had been receiving etanercept 25 mg twice weekly for at least 4 years. Both ERA and LRA extension studies are ongoing. Patient-reported outcome assessments included improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI), proportions of patients achieving an improvement in HAQ-DI > or = 0.22 points, patients exhibiting worsening of HAQ-DI and patients achieving an HAQ-DI score of 0. RESULTS: Elderly patients, with either ERA or LRA, had significantly worse baseline mean HAQ-DI scores than younger patients (p < 0.05, Student's t-test) in most studies, indicating greater disability. Improvement in HAQ-DI was greatest during the first 3 months after starting etanercept treatment in the controlled phase and appeared to be sustained over 3-6 months in patients with early or DMARD-refractory RA. Across the various controlled trials, mean improvements from baseline in HAQ-DI ranged from 0.39 to 0.92 points in elderly patients and from 0.57 to 1.00 points in younger patients. Patients with ERA and LRA, regardless of age group, maintained their improvement in HAQ-DI throughout the open-label extension trials for up to a total of 6 years of etanercept therapy. Change from baseline in HAQ-DI was moderately correlated with 28-joint Disease Activity Score within each age group across the multiple trials. CONCLUSION: Both elderly and younger patients with RA treated with etanercept exhibited similar and rapid improvements in functional status during controlled studies, and these improvements were sustained during open-label extension trials.
16736520 Comparison of the response to infliximab or etanercept monotherapy with the response to co 2006 Jun OBJECTIVE: To compare outcome at 6 months in unselected "real-world" patients with rheumatoid arthritis treated with etanercept or infliximab as either monotherapy, cotherapy with methotrexate (MTX), or cotherapy with another disease-modifying antirheumatic drug (DMARD). METHODS: A total of 2,711 subjects starting treatment with their first biologic agent (1,453 infliximab and 1,258 etanercept) were followed up for 6 months. Outcome was assessed using the European League Against Rheumatism (EULAR) response criteria. Ordinal regression was used to model the response in the MTX and other DMARD cotherapy groups relative to the monotherapy group separately for the 2 anti-tumor necrosis factor alpha agents, after adjusting for baseline differences. RESULTS: Etanercept-treated patients had an increased likelihood of achieving a higher EULAR response category with cotherapy with MTX (odds ratio [OR] 2.0, 95% confidence interval [95% CI] 1.5-2.7) and with another DMARD (OR 1.2, 95% CI 0.9-1.6) as compared with monotherapy. For infliximab-treated patients, the likelihoods were 1.4 (95% CI 0.9-2.0) for MTX and 1.3 (95% CI 0.8-2.1) for other DMARDs versus monotherapy. Cotherapy with MTX or another DMARD produced significantly higher rates of remission with etanercept (12% and 11%, respectively) as compared with etanercept monotherapy (5%). Infliximab-treated patients showed similar remission rates in the MTX and other DMARD cotherapy groups (8% and 5%, respectively) as in the monotherapy group (7%). CONCLUSION: In this study of real-world patients, the use of MTX and, to a lesser extent, other DMARDs as cotherapy with etanercept was associated with a higher likelihood of response. Although the infliximab guidelines suggest that MTX be used as cotherapy, in clinical practice, both monotherapy and cotherapy with DMARDs other than MTX are used. These data suggest that either of the latter strategies may be useful in patients who are intolerant to MTX.
17235556 Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha 2007 May Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still under survey. The purpose of this study was to evaluate and compare the efficacy of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in reducing disease activity in RA. Seventy-eight patients with active RA underwent a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF-alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2, 6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with RA resistant to MTX were included in groups receiving LEF or a biologic agent. During follow-up, patients' characteristics, disease characteristics, and clinical and laboratory data were registered. RA activity was evaluated using the ESR, tender and swollen joint counts, the duration of morning stiffness, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70 criteria. All groups revealed statistically significant improvement in all disease activity parameters measured. The percentage improvements were similar in groups treated with MTX and LEF and--except for VAS--significantly greater in the group treated with a biologic agent. Disease activity assessed by DAS 28 decreased significantly in all groups: the results were comparable in groups treated with MTX and LEF and significantly more prominent in the group treated with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted, respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83 and 50% in a biologic agent group. The study revealed equal effectiveness of MTX and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a TNF-alpha blocker combined with MTX was higher than that of each conventional DMARDs, especially with regard to ACR 70 criteria (considerable improvement after treatment). LEF was equally effective as MTX in patients unable to continue MTX treatment due to the drug's ineffectiveness.
16609887 Protective effects of thymoquinone and methotrexate on the renal injury in collagen-induce 2006 Nov The goal of this investigation was to study the protective effects of thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in rats. On day 0 under ether anesthesia, the experimental groups were immunized with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and emulsified in Freund's incomplete adjuvant. Control rats were gavaged with vehicle, whereas CII was administered intradermally. In addition, arthritis treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3 weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a week for 3 weeks starting on day 0). A significant decrease in the incidence and severity of arthritis by clinical and radiographic assessments was found in recipients of therapy, compared with that of controls. The MTX treatment significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in arthritic rats. Likewise, TQ treatment was also able to reduce significantly (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The histopathologic abnormalities are consistent with the hydropic epithelial cell degenerations and moderate tubular dilatation in the some proximal and distal tubules. The severity of the degenerative changes in most of the shrunken glomerules and vascular congestion were also observed in arthritic animals. Preventive treatment of TQ and especially MTX significantly inhibited kidney dysfunction and this histopathologic alterations. These studies indicate that TQ can be used similar to MTX as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.
18645332 Rituximab is useful in the treatment of Felty's syndrome. 2008 Jul Felty's syndrome is regarded as a severe variant of rheumatoid arthritis (RA) that develops in less than 1% of patients with RA. It consists of a triad of RA, splenomegaly, and leukopenia, which tends to develop after a long course of RA. Treatment of neutropenia is mainly comprised of disease-modifying antirheumatic drugs including methotrexate, hydroxychloroquine, auronofin, penicillamine, glucocorticoids, and granulocyte monocyte colony stimulating factor. Recently, there has been a growing interest in the biologic agent rituximab in the treatment of Felty's syndrome. To our knowledge, only one previous case of rituximab being beneficial in the treatment of Felty's syndrome has been reported. We report the case of a 60-year-old man with Felty's syndrome in whom treatment with rituximab led to a sustained neutrophil response and marked symptomatic improvement in the form of decrease in the size of rheumatoid nodules and better pain control.
18603660 Adjunctive anakinra in patients with active rheumatoid arthritis despite methotrexate, or 2008 Sep OBJECTIVE: To assess the efficacy and safety of anakinra (ANK) as an add-on therapy in RA patients with inadequate response to monotherapy with non-biological DMARDs. METHODS: A 48-week comparative, prospective study of patients with active RA [mean 28-joint disease activity score (DAS28): 6.81], despite MTX (n = 48), or LEF (n = 42), or CSA (n = 38) treatment, in whom ANK (100 mg/daily SC) was given with corticosteroid cream topical application. RESULTS: At 24 and 48 weeks the patient percentages meeting the ACR20 response criteria were 57 and 73%, respectively, 33 and 41% met ACR50, while 15 and 23% met ACR70. Significant improvements in number of swollen and tender joints, HAQ, pain, global disease assessment, CRP and haemoglobin from baseline to 24 and 48 weeks were evident. DAS28 decreased at 24 weeks (- 1.68; 95% CI - 1.46, - 1.90; P < 0.0001), as well as at study end (- 2.24; 95% CI - 2.01, - 2.47; P < 0.0001). Subgroup analysis revealed a significantly weaker response in terms of pain and DAS28 in patients treated with concomitant CSA. The most common ANK-related adverse event was injection-site reaction (29%), being less frequent in male patients, as well as in patients treated with CSA. There were 17 withdrawals, 6 of them due to inefficacy. No opportunistic infections or new safety signals were observed. CONCLUSION: Considering the limitations of an open-label study, addition of ANK appears to be an effective and well-tolerated treatment option for many RA patients with inadequate responses to non-biologic DMARDs in clinical practice.
17558834 Systemic immunomodulatory therapy in severe dry eye secondary to inflammation. 2007 Mar PURPOSE: To report four patients with unusually severe acute keratitis sicca secondary to lacrimal tissue and ocular surface inflammation who eventually required systemic immunosuppressive therapy. METHODS: Observational case series of four patients with extremely severe acute dry eye syndrome who were profoundly disabled by pain and photophobia (to the extent of staying in dark rooms) despite aggressive conventional therapy. Clinical data including visual acuities, other treatments administered for dry eye, systemic medical conditions, Schirmer and rose bengal staining results, degree of conjunctival injection, and medications were recorded. All four patients were treated with systemic immunomodulatory therapy. RESULTS: All four patients were female with a mean age at presentation of 40 years (range 22-58 years), and all had systemic autoimmune diseases: systemic lupus erythematosus (SLE) and Sjogren's syndrome (n = 2), Sjogren's syndrome (n = 1), rheumatoid arthritis (RA) and psoriasis (n = 1). Schirmer test values at onset ranged from 0 to 2 mm. All patients had failed aggressive lubrication, topical cyclosporine, lid care, and punctual plugs. In two patients, serum tears and hyphrecation punctal occlusion were tried without success. Various systemic immunosuppressive agents were used to control inflammation of the lacrimal glands: methotrexate and cyclosporine A (patient 1), cyclosporine A (patient 2), prednisone (patient 3), and methotrexate and infliximab (patient 4). Treatment with systemic immunomodulatory agents resulted in resolution of the acute inflammatory assault on the lacrimal glands and control of signs and symptoms of keratoconjunctivitis sicca in all four patients, and visual acuities improved in all of them. Post-treatment Schirmer values ranged from 7 to 10 mm. CONCLUSION: Systemic immunosuppressive agents may be required in the treatment of recalcitrant primary and secondary Sjogren's syndrome caused by systemic autoimmune conditions. We show that systemic immunomodulatory therapy leads to significantly improved tear production and resolution of the keratoconjunctivitis in these rare but severe cases.