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ID PMID Title PublicationDate abstract
20504106 The efficacy and safety of golimumab in the treatment of arthritis. 2010 Jul IMPORTANCE OF THE FIELD: Twenty-five years ago, rheumatoid arthritis (RA) was a relentless disease, treated symptomatically because of the lack of effective, well tolerated medications which could halt disease in most patients. The introduction of methotrexate, sulfasalazine and leflunomide, and aggressive treatment, changed the prognosis of RA in the 1990s. Biologic therapies have dramatically changed the long-term prognosis of patients with rheumatoid and psoriatic arthritis and ankylosing spondylitis. AREAS COVERED IN THIS REVIEW: Unfortunately, no one single agent is fully effective in every patient. For this reason, another agent, golimumab (GLM), a TNF-alpha inhibitor (TNF-I) was developed. The basis of this review is all peer-reviewed manuscripts on GLM in the treatment of RA, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) found in Pub Med. and Medline from 2000 to 2010 and abstracts presented at the major rheumatology congresses within the past five years. WHAT THE READER WILL GAIN: This review describes the efficacy and safety of GLM and should enable an understanding of the benefit-risk profile of GLM in the treatment of RA, PsA and AS. TAKE HOME MESSAGE: GLM is effective and has a safety profile similar to other TNF-I in the treatment of RA, AS and PsA.
19062243 [Pneumocystis pneumonia among patients with systemic diseases]. 2009 Feb The termPneumocystis carinii is now reserved for the animal form of the disease, for humans Pneumocystis jiroveci is appropriated. Incidence of pneumocystis pneumonia (PCP) among patients with systemic rheumatic diseases varies from 0.2% for rheumatoid arthritis to up 12% for Wegener's granulomatosis. Clinical and radiological presentation of pneumocystis pneumonia among non-VIH patients is often difficult to diagnose and the installation can be abrupt. Most of cases of PCP occur during the first 3 months following the beginning of immunosuppressant agents. Mortality during PCP is high with an average of 40% of death, rising 60% in case of mechanical ventilation. Prophylaxis of PCP is needed (without support by randomised studies) for patients with Wegener's granulomatosis, in case of cyclophosphamide or high-dose of methotrexate use except for rheumatoid patients, if a simultaneous treatment by corticosteroids and immunosuppressant agent is required, if a prolonged corticosteroid treatment (> 2 months) is used with dose of prednisone-equivalent > 16mg per day or > 20mg per day > 1month associated with one or more risk factors of PCP among advanced age, denutrition or deep lymphopenia. The best prophylaxis of PCP is cotrimoxazole.
19579967 The efficacy of disease modifying anti-rheumatic drugs in rheumatoid arthritis in local pa 2009 Feb 15 The primary objective of the study is to assess the efficacy of the 'Disease Modifying AntiRheumatic Drugs (DMARDs) on the disease activity in Rheumatoid Arthritis (RA) in the local patients of Karachi. The secondary objective is to evaluate whether the combination of two concurrent DMARDs (Combination Therapy) is superior to a single DMARD (Mono-therapy). This is an open labeled retrospective case series. One hundred and five consecutive patients fulfilling 1987 ACR criteria for the diagnosis of RA were initially selected from the case notes of out patients department. Sixty nine patients fulfilled the inclusion criteria and were finally recruited for analysis. Details of the Tender Joint Count (TJC), Swolen Joint Count (SJC), Patient Global Assessment (PGA) and ESR were obtained at six weeks, three months, six months and one year. Out of the 69 patients studied 48 were in the mono-therapy group and 21 in the combination therapy group. Methotrexate (MTX) was the most commonly used single DMARD (75%) as well as the most frequent component of the combination groups (85%). The TJC, SJC and PGA analyses of all patients show that DMARDs are effective agents for clinically controlling RA activity. The speed of their beneficial effect is slow and unlike analgesics and NSAIDS, may take up to six weeks to start working. The 6 week responses showed 32.49% improvement in TJC, 33.19% improvement in SJC and 59% better responses in PGA. This response continued to show further improvement and at six months when TJC improved by 63.41%, SJC by 53.21% and PGA with 81% better responses. After 6 months the response reached a plateau but nevertheless maintained until 1 year with improvements in TJC by 66.23%, SJC by 56.48% and PGA with 88.23% better responses. The changes in ESR did not go parallel with the other three outcome measures. The mean baseline ESR of 56 reduced to 44 at 6 weeks but rose again gradually to 54 at 1 year. The sub-group analysis did not show the overall superiority of combination therapy over mono-therapy. DMARDs are effective in controlling disease activity in RA. Their effect starts slowly over 6 week and may take up to 6 months to show full benefits. The beneficial effect was maintained for at least 1 year. Sub-group analysis did not show any advantage of combination therapy over mono-therapy in this series of patients. Methotrexote being the most frequently used DMARDs in both groups and being most cost effective agent seems to be the most useful drug in RA in the developing world.
20476867 Tacrolimus for the treatment of active rheumatoid arthritis: a systematic review and meta- 2010 Aug OBJECTIVE: The aim of this study was to assess the efficacy and safety of tacrolimus in patients with active rheumatoid arthritis (RA). METHODS: We surveyed randomized controlled trials (RCTs) and open-label studies that examined the efficacy and toxicity of tacrolimus in disease-modifying anti-rheumatic drug (DMARD)--and methotrexate (MTX)-resistant or -intolerant patients with active RA patients using Medline, the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. The results are presented as risk ratios (RRs), weighted mean differences (WMDs), or standardized mean differences (SMDs). Open-label studies were included in the systematic review. RESULTS: The four RCTs included 1014 DMARD-resistant or -intolerant patients with DMARD-resistant or -intolerant RA. Median follow-up duration was 6 (range 4-6) months. American College of Rheumatology 20, 50, and 70% (ACR20, ACR50, and ACR70) response rates were significantly higher in the tacrolimus 3 mg/day group (n = 390) than in the controls (n = 402) [primary efficacy outcome, ACR50; risk ratio (RR) 2.583, 95% confidence interval (CI) 1.095-6.092, p = 0.030], and efficacies in the tacrolimus 1.5-2 mg/day group showed a similar pattern. Patients treated with tacrolimus withdrew from treatment because of adverse events (n = 222) (primary safety outcome, withdrawals due to adverse events; RR 1.475, 95% CI 0.895-2.187, p = 0.053) more frequently than controls (n = 231), although this was not significant. All four open-label studies found that tacrolimus was safe, well-tolerated, and provided clinical benefits. CONCLUSIONS: Tacrolimus, at dosages of 1.5-3 mg/day, was found to be effective in DMARD-resistant or -intolerant patients with active RA.
20482403 Rituximab treatment for persistent scleritis associated with rheumatoid arthritis. 2010 Jun PURPOSE: To report a clinical case of a patient with severe scleritis associated with rheumatoid arthritis (RA) refractive to conventional treatment that was treated effectively with rituximab. METHODS AND RESULTS: A 55-year-old man with RA, on etanercept and oral methotrexate, was referred with diagnosis of acute stromal keratitis, anterior uveitis, and anterior nodular scleritis in his right eye. Cyclophosphamide induced complete regression of acute stromal keratitis and anterior uveitis, but scleritis was still active and persistent. After two 1000-mg infusions of rituximab, scleritis regressed completely and is still in remission 9 months after the second rituximab infusion, without any concomitant use of oral steroids. CONCLUSION: Rituximab may be a treatment alternative in severe scleritis that is refractive to conventional therapy. Considering its safety profile, further studies are needed to refine its mechanism of action, optimal indications, and dosing in ocular inflammation.
20085505 Methotrexate compliance among patients with rheumatoid arthritis: the influence of disease 2010 May OBJECTIVE: To assess methotrexate (MTX) compliance among rheumatoid arthritis (RA) patients. METHODS: Using prescription data, we conducted a 10-year longitudinal study among RA patients who were first-time MTX users. MTX compliance was expressed as the continuous measure of medication gaps (CMG), that is the proportion of treatment gaps compared with the total observation period stratified by age, sex, C-reactive protein (CRP), haemoglobin, co-morbidity, concurrent medication, and disease duration. Multiple linear regression analysis was used to assess the influence of disease activity, disease duration, and co-morbidity on compliance. RESULTS: A total of 941 RA patients redeemed 7501 MTX prescriptions during our study period. Overall, the patients had gaps in 12.3% of the observation period corresponding to a mean period not covered with MTX of 1.5 months/year if all participants were followed for 1 year. Patients with CRP > 32 mg/L had a lower mean CMG than patients with CRP < 8 mg/L [adjusted CMG difference -0.04, 95% confidence interval (CI) -0.07 to - 0.02]. Patients with a disease duration < 1 year had a lower mean CMG than patients with a disease duration between 1 and 5 years (adjusted CMG difference 0.01, 95% CI -0.01 to 0.04). Patients with a diagnosis of ulcer/mild liver disease had a higher mean CMG than patients without this diagnosis (adjusted CMG difference 0.04, 95% CI 0.004-0.084). CONCLUSION: MTX compliance was generally high among RA patients. Compliance decreased with increasing disease duration, low to moderate disease activity, and the presence of a diagnosis of ulcer/mild liver disease.
19247593 [A novel treatment option in rheumatoid arthritis: abatacept, a selective modulator of T-c 2009 Abatacept is the first drug in a new class of disease-modifying anti-rheumatic drugs known as selective modulators of T-cell costimulation. The efficacy of abatacept in the treatment of rheumatoid arthritis (RA) has been shown in several clinical phase II and phase III trials, wherein abatacept was used in monotherapy, either in combination with methotrexate (MTX) after MTX-failure, in combination with MTX after failure of anti-TNF-alpha therapy or in combination with TNF-alpha blockers. In addition, the combination of abatacept/MTX was directly compared with infliximab/MTX. Current data on abatacept demonstrate an encouraging safety profile of this drug. The number of adverse events in patients on abatacept is comparable to that in patients treated with other biologics. Severe infections, however, are more common in abatacept-treated patients than in placebo-treated patients. Opportunistic infections are rare in patients with abatacept and the frequency of malignancies is not higher than expected in RA-patients. Additional studies are now warranted to get more information on rare adverse events and long-term unwanted effects.
20488885 Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo 2010 Sep OBJECTIVES: This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. METHODS: Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. RESULTS: At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. CONCLUSIONS: Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.
20390116 [Italian consensus on the recommendations about the use of methotrexate for the treatment 2010 Jan OBJECTIVE: To develop a set of national evidence-based recommendations for the use of Methotrexate (MTX) in daily clinical practice. METHODS: A panel of 37 Italian Rheumatologists reviewed 10 international recommendations formulated during the "3E (Evidence, Expertise, Exchange) initiative" for the year 2007-8, following a systematic literature search in Medline, Embase, Cochrane Library, and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts and the revision of selected papers and the appraisal of Oxford levels of evidence. Moreover, the same panel by the same methodology formulated further 5 recommendations on topics previously selected by Italian representatives to 3E initiative. The agreement about the set of proposed recommendations was stated by a consensus process and the potential impact on clinical practice was assessed. RESULTS: International Recommendations were analysed and changed when appropriate. In addition, 5 national recommendations were developed by identifying 6371 references, selecting and evaluating the 29 ones satisfying Evidence Based Medicine principles. CONCLUSIONS: A set of 15 national recommendations for the use of MTX in daily clinical practice was developed. These recommendations are evidence-based and integrate the expertise of a large panel of Italian rheumatologists.
19565475 The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: R 2009 Jul OBJECTIVE: To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response. METHODS: Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks. RESULTS: By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms. CONCLUSION: Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.
20195397 Description of the efficacy and safety of three new biologics in the treatment of rheumato 2010 Mar English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab. All three drugs were effective in methotrexate-naïve, methotrexate-incomplete responders, and tumor-necrosis-factor-failure rheumatoid arthritis patients. Of the three, only abatacept has been tested in a head-to-head trial with infliximab, in which it was found to be equivalent to infliximab. Golimumab resulted in a more modest improvement than the others in methotrexate-naïve patients, although no direct comparisons among the three drugs were possible or appropriate. Descriptive analysis of adverse events showed that patients receiving abatacept, golimumab, and tocilizumab were subject to more adverse events than controls overall, as expected. In the abatacept studies, a few cases of tuberculosis, more cardiovascular events and gastrointestinal bleedings and more basal cell carcinoma were seen. Golimumab was associated with more skin rashes and pneumonia, while tocilizumab was associated with increased lipids, more liver-function abnormalities, and neutropenia. These new medications are useful additions to the rheumatologic armamentarium and represent greater convenience (golimumab) or different mechanisms of action (abatacept and tocilizumab) than tumor-necrosis-factor inhibitors for treating rheumatoid arthritis. As expected, some adverse events occur when using these drugs and patients need to be watched carefully.
20091667 Golimumab for rheumatoid arthritis. 2010 Jan 20 BACKGROUND: Golimumab is a humanized inhibitor of Tumor necrosis factor-alpha, recently approved by the Food and Drug Administration (FDA) for the treatment of Rheumatoid arthritis (RA). OBJECTIVES: The objective of this systematic review was to compare the efficacy and safety of golimumab (alone or in combination with DMARDs or biologics) to placebo (alone or in combination with DMARDs or biologics) in randomized or quasi-randomized clinical trials in adults with RA. SEARCH STRATEGY: An expert librarian searched six databases for any clinical trials of golimumab in RA, including the Cochrane Central Register of Controlled Trials (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials databases. SELECTION CRITERIA: Studies were included if they used golimumab in adults with RA, were randomized or quasi-randomized and provided clinical outcomes. DATA COLLECTION AND ANALYSIS: Two review authors (JS, SN) independently reviewed all titles and abstracts, selected appropriate studies for full review and reviewed the full-text articles for the final selection of included studies. For each study, they independently abstracted study characteristics, safety and efficacy data and performed risk of bias assessment. Disagreements were resolved by consensus. For continuous measures, we calculated mean differences or standardized mean differences and for categorical measures, relative risks. 95% confidence intervals were calculated. MAIN RESULTS: Four RCTs with 1,231 patients treated with golimumab and 483 patients treated with placebo were included. Of these, 436 were treated with the FDA-approved dose of golimumab 50 mg every four weeks. Compared to patients treated with placebo+methotrexate, patients treated with the FDA-approved dose of golimumab+methotrexate were 2.6 times more likely to reach ACR50 (95% confidence interval (CI) 1.3 to 4.9; P=0.005 and NNT= 5, 95% confidence interval 2 to 20), no more likely to have any adverse event (relative risk 1.1, 95% Cl 0.9 to 1.2; P=0.44), and 0.5 times as likely to have overall withdrawals (95% Cl 0.3 to 0.8; P=0.005). Golimumab-treated patients were significantly more likely to achieve remission, low disease activity and improvement in functional ability compared to placebo (all statistically significant). No significant differences were noted between golimumab and placebo regarding serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events and inefficacy and deaths. No radiographic data were reported. AUTHORS' CONCLUSIONS: With an overall high grade of evidence, at the FDA-approved dose, golimumab is significantly more efficacious than placebo in treatment of patients with active RA , when used in combination with methotrexate. The short-term safety profile, based on short-term RCTs, is reasonable with no differences in total adverse events, serious infections, cancer, tuberculosis or deaths. Long-term surveillance studies are needed for safety assessment.
19054823 Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy wit 2009 Jul OBJECTIVE: To evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis. METHOD: A systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy. RESULTS: A total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations. CONCLUSION: In DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.
20950126 The number needed to treat for second-generation biologics when treating established rheum 2011 Jan OBJECTIVE: To evaluate the number needed to treat (NNT) and the number needed to harm (NNH) of the second-generation biologics abatacept, certolizumab, golimumab, rituximab, and tocilizumab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX). METHODS: A systematic literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane Register of Controlled Trials was conducted up to 1 November 2009. We selected any published randomized, double-blind, MTX-controlled study including RA patients with a mean disease duration of at least 5 years before entering a pivotal trial on second-generation biological therapy. Studies eligible for inclusion involved patients, who had previously shown inadequate response to conventional disease-modifying anti-rheumatic drug (DMARD) therapy. Pre-specified binary outcomes were extracted with a preference for 1-year data (6-month data were used if no data were available for 1 year). Two reviewers independently extracted the data necessary to estimate the absolute measures in a non-responder intention-to-treat (ITT) analysis. RESULTS: Five randomized controlled trials, one for each of the drugs, were selected and data extracted according to published data at endpoint for American College of Rheumatology 50% (ACR50)-responding patients, and withdrawals due to adverse events. NNT ranged from four to six treated patients to achieve one ACR50 response, while withdrawals due to adverse events were few and non-significant compared to the placebo group, except for rituximab administered as 1000 mg. CONCLUSION: Comparable efficacy was shown by the five biological agents studied, with few adverse events. However, for rituximab, tocilizumab, and golimumab, only 6-month data were available, hampering the external validity with regard to long-term efficacy and tolerability. A low dose (500 mg) of rituximab may be as effective as the recommended dose of 1000 mg.
19847432 The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL 2010 Nov Objective of the study is to assess the effects of adalimumab and MTX therapy on peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10). Peripheral blood samples were taken for laboratory evaluation at week 0 and week 12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+) cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers were included as normal controls. Results showed that (1) DAS28 in both groups improved at week 12 compared to week 0 (3.9 ± 1.3 vs. 6.4 ± 1.4 and 3.2 ± 0.9 vs. 5.2 ± 0.9, respectively). (2) The percentage and MFI of peripheral CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to normal controls (1.64 ± 0.97% vs. 0.75 ± 0.20%, p < 0.01; and 29.8 ± 9.7 vs. 19.8 ± 4.6, p < 0.05, respectively), and positively correlated with ESR and DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after treatment (from 1.60 ± 0.78% to 1.28 ± 0.41%, and from 17.15 ± 14.53 pg/ml to 6.97 ± 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression in active RA patients was significantly lower comparing to normal controls, and negatively correlated with ESR. Baseline Th17 percentage of RA patients negatively correlated with DAS28 improvement after treatment. In conclusion, adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6 level in RA patients. Baseline Th17 level negatively predicts the effect of adalimumb/MTX treatment.
20039396 Humoral responses after influenza vaccination are severely reduced in patients with rheuma 2010 Jan OBJECTIVE: For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. METHODS: Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity. RESULTS: Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination. CONCLUSION: Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.
20714691 Adverse effects of low dose methotrexate in rheumatoid arthritis patients. A hospital-base 2010 Aug OBJECTIVE: To evaluate the side effects of methotrexate (MTX) in rheumatoid arthritis (RA) patients and to evaluate the possible predisposing variables. METHODS: A retrospective analysis conducted for all patients diagnosed with RA and treated with MTX over 3-years (January 2006 to December 2008) at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Frequency of MTX side effects and the predictive variables were recorded and analyzed statistically. RESULTS: Out of 116 RA patients, 71 patients used MTX. The most frequent side effect was gastrointestinal (GIT) disturbance in 31%, followed by central nervous system symptoms in 18%, hepatotoxicity in 14%, stomatitis and alopecia in 10% each, macrocytosis 7%, fever, malar rash and pancytopenia in 4%, and MTX-induced lung injury with increase in the size of rheumatoid nodule in 1% of patients. By Logistic regression analysis, renal impairment was the most significant variable increasing the risk of the side effects (OR=7.14, p<0.05). Other associated variables were male-gender, non-Saudi nationality, smoking, steroids use, hypoalbuminemia, and the presence of extra-articular manifestations. CONCLUSION: Methotrexate is the most commonly drug used in the treatment of RA. Gastrointestinal disturbances were the most common side effect while lung involvement was the least. The impact of each clinical variable on MTX side effects requires paying more attention on the disease management as not all variables can be considered as risk factors.
20112376 Methotrexate polyglutamate concentrations are not associated with disease control in rheum 2010 Feb OBJECTIVE: There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlu(n) concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment. METHODS: A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed. RESULTS: The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu(5). RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu(n) concentration and adverse effects. CONCLUSION: In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu(n) concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlu(n) concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu(n) concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu(n) concentrations in patients receiving long-term treatment with MTX.
19826823 Scoring evaluation for histopathological features of synovium in patients with rheumatoid 2010 Jan The present study was performed to evaluate the synovium in patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor alpha agents (anti-TNFalpha). Synovial tissue specimens were obtained during total knee arthroplasty (TKA) from 42 RA patients (12 men, 30 women). Twenty-one RA patients were given anti-TNFalpha agents (infliximab, n = 12; etanercept, n = 9), while the remaining 21 RA patients were given no such agents.The histopathological findings were compared between specimens from these groups using the histological scoring system reported by Rooney, which consists of six items:degree of synovial hyperplasia, fibrosis, number of blood vessels, perivascular lymphocyte infiltration, focal aggregates of lymphocytes, and diffuse infiltrates of lymphocytes.Clinical laboratory data including C-reactive protein(CRP), matrix metalloproteinase-3 (MMP-3), and disease activity scores including a 28-joint count (DAS28), disease duration, methotrexate (MTX) dose, and glucocorticoid dose were also assessed before surgery. There were no significant differences in total score between anti-TNFalpha and no anti-TNFalpha groups. However, significant differences were observed in scores of synoviocyte hyperplasia and perivascular infiltrates of lymphocytes between the groups. These results suggested that these agents have a suppressive effect on cell proliferation in the lining layer and on perivascular lymphocyte infiltration. However, further studies are necessary to elucidate the mechanisms of these effects.
19458163 Methotrexate in combination with sulfasalazine is more effective in rheumatoid arthritis p 2009 Jul OBJECTIVES: For pharmacological reasons, the effect of the combination of MTX and SSZ may be different in RA patients who are naïve to these drugs compared to patients with an insufficient response to one of them. Therefore, we compared the results of randomized controlled trials (RCTs) on the combination of MTX and SSZ in naïve patients and in patients with an insufficient response to SSZ. METHODS: A systematic literature search was performed to identify RCTs that compared the MTX-SSZ combination to either drug alone. The databases MEDLINE and the Cochrane Clinical Trials registry were searched from 1966 up to April 2007. The efficacy of the single therapeutic agents or their combination was assessed using the mean change in the disease activity score (DAS) and the ACR improvement criteria. RESULTS: Four RCTs were identified to compare the efficacy of the combination MTX-SSZ to the efficacy of either drug alone. Two parallel trials were performed with patients naïve to both drugs and two add-on trials were performed in SSZ failures. In the trials with naïve patients, the mean DAS changes for the combination MTX and SSZ pointed to a sub-additive efficacy. In the trials with patients who previously failed to SSZ, the mean DAS changes for the combination MTX and SSZ indicated additive efficacy. CONCLUSIONS: In RA, addition of MTX to SSZ is a therapeutic option in SSZ failures, whereas combination of MTX and SSZ in DMARD-naïve patients has no added value.