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Clinical Rheumatology Apr 2022Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis.... (Review)
Review
INTRODUCTION
Myasthenia gravis is an autoimmune disease affecting the neuromuscular junction, often associated with other autoimmune diseases, including rheumatoid arthritis. Patients with rheumatoid arthritis present an increased prevalence of myasthenia gravis compared to the general population. While these two diseases share some therapeutic options, such as glucocorticoids, methotrexate, and rituximab, there are no guidelines for treating concomitant disease. We aim to review the available evidence and to discuss the efficacy and safety of the therapeutic options in patients with rheumatoid arthritis associated with myasthenia gravis.
METHOD
We described three patients with rheumatoid arthritis associated with myasthenia gravis and we performed a systematic review of the associated literature.
RESULTS
A 48-year-old man and two women (48 and 55 years old) with concomitant diagnoses of active rheumatoid arthritis and well-controlled myasthenia gravis are described. They were treated with methotrexate, leflunomide, upadacitinib, and adalimumab. None of them experienced changes in their myasthenic symptoms. We found 9 additional cases from our literature review. Methotrexate, rituximab, upadacitinib, diphenyl sulfone, auranofin, and loxoprofen sodium did not show an impact on the seven patients with previously well-controlled myasthenia. Glucocorticoids, methotrexate, and rituximab proved effective in active myasthenia gravis and arthritis. Conflicting data emerged for Tumor-necrosis factor inhibitors.
CONCLUSIONS
Although the available evidence remains scarce, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options. The role of tumor-necrosis factor inhibitors remains uncertain. Eventually, Janus Kinase inhibitors are a novel interesting option for these patients. Key Points • To date, the only evidence on the treatment of patients with rheumatoid arthritis and concomitant myasthenia gravis derives from case reports. • Based on the review of the available case reports and on the cases we described, we consider glucocorticoids, methotrexate, and rituximab as safe and effective options, while the role of Tumor-necrosis factor inhibitors remains uncertain. • Based on the cases we described, Janus Kinase inhibitors are a novel interesting option for patients with concomitant rheumatoid arthritis and myasthenia gravis.
Topics: Adalimumab; Arthritis, Rheumatoid; Female; Humans; Janus Kinase Inhibitors; Male; Methotrexate; Middle Aged; Myasthenia Gravis
PubMed: 35031874
DOI: 10.1007/s10067-022-06062-w -
The Cochrane Database of Systematic... 2000Auranofin is an oral gold compound used for the treatment of rheumatoid arthritis RA. The use of auranofin has declined in the past few years, perhaps due in part to... (Review)
Review
BACKGROUND
Auranofin is an oral gold compound used for the treatment of rheumatoid arthritis RA. The use of auranofin has declined in the past few years, perhaps due in part to conflicting results from different studies.
OBJECTIVES
To estimate the short-term efficacy and toxicity of auranofin for the treatment of (RA) SEARCH STRATEGY: We searched MEDLINE and EMBASE up to December 1998, the Cochrane Controlled Trials Register (CCTR) version 4, 1998, and the Cochrane Musculoskeletal Group Specialized Register. A hand search was also done of the reference lists of the trials retrieved from the electronic search.
SELECTION CRITERIA
All randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing auranofin against placebo in patients with RA DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using a validated assessment tool (Jadad 1996). Rheumatoid arthritis outcome measures were extracted from the publications for the 6-month endpoint. The pooled analysis was performed using standardized mean differences (SMDs) for joint counts, pain and global assessments. The weighted mean difference (WMD) was used for ESR. Toxicity was evaluated with pooled odds ratios for withdrawals and adverse reactions. A chi-square test was used to assess heterogeneity among trials. In the presence of heterogeneity, random effects models were used. Otherwise, the data was pooled assuming fixed effects.
MAIN RESULTS
A statistically significant benefit was observed for auranofin when compared to placebo for tender joint scores, pain, patient and physician global assessments and ESR. The SMD between treatment and placebo was -0.39 (95% CI -0.54, -0.25) for tender joint scores, -0.08 (95% CI -0.22, -0.07) for swollen joint scores, and the WMD was -4.68 (95% CI -6.59, -2.77) for pain scores and -9.85mm (95% CI -16.46, -3.25) for ESR. Withdrawals from adverse reactions were 1.5 times higher in the auranofin group OR = 1.52 (95% CI 0.94, 2.46) but this result was not statistically significant. Patients receiving placebo were three times more likely to discontinue treatment because of lack of efficacy than patients receiving auranofin: OR=0.31 (95% CI: 0.21, 0.44).
REVIEWER'S CONCLUSIONS
Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Auranofin; Humans
PubMed: 10796461
DOI: 10.1002/14651858.CD002048 -
The Cochrane Database of Systematic... 2000To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. (Review)
Review
OBJECTIVES
To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis.
SEARCH STRATEGY
We searched Medline up to 1995, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings and contacting drug companies. All languages were included in the initial search.
SELECTION CRITERIA
All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. The main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include Acute Phase Reactants, Disability, Pain, Patient Global Assessment, Physician Global Assessment, Swollen joint count, Tender joint count and radiographic changes of joints in any trial of 1 year or longer [Tugwell 1993], and the change in pooled disease index. Only English trials were included in the review.
DATA COLLECTION AND ANALYSIS
Data were independently extracted from the published reports by two of the reviewers. An independent blinded quality assessment was also performed.
MAIN RESULTS
Nineteen randomized trials were identified of which eleven were included in the quantitative analysis with data from 777 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.43 DI units, 95% CI 0. 28-0.59). There was insufficient data to examine toxicity.
REVIEWER'S CONCLUSIONS
Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Auranofin; Azathioprine; Dermatologic Agents; Etretinate; Fumarates; Humans; Immunosuppressive Agents; Methotrexate; Sulfasalazine
PubMed: 10796328
DOI: 10.1002/14651858.CD000212 -
The Cochrane Database of Systematic... 2001Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side... (Review)
Review
BACKGROUND
Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Gold compounds are immunosuppressive agents and have benefits in the treatment of a number of inflammatory disorders. They have therefore been identified as an potentially useful agents in the treatment of chronic severe asthma both in terms of possible efficacy and as steroid sparing agents.
OBJECTIVES
The objective of this review was to assess the effects of adding gold to oral steroids in the treatment of chronic steroid dependent asthmatics.
SEARCH STRATEGY
The Cochrane Airways Group trials register and reference lists of identified articles were searched.
SELECTION CRITERIA
Randomised trials looking at the addition of gold compared to placebo in adult steroid dependent asthmatics.
DATA COLLECTION AND ANALYSIS
Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information.
MAIN RESULTS
Three trials fulfilled the criteria for inclusion in the review and a total of 376 patients were recruited into these studies. Data from 311 patients could be analysed. There was a small but significant treatment effect for gold in terms of steroid dose reduction (Peto Odds Ratio 0.51, 95% confidence intervals 0.31,0.83). No meta-analysis could be done for measures of lung function although overall there were few changes suggesting a positive benefit for gold. There were trends suggestive of adverse effects but no significant changes for gold treated patients with respect to proteinuria (Peto Odds Ratio 1.4, 95% confidence intervals 0.6, 3.3) dermatitis/eczema Peto Odds Ratio 2.1, 95% confidence intervals 0.9, 4.7).
REVIEWER'S CONCLUSIONS
The changes seen in these trials are small and probably of limited clinical significance. Given the side effects of gold and necessity for monitoring the use of gold as a steroid sparing agent in asthma cannot be recommended.
Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Auranofin; Aurothioglucose; Humans; Randomized Controlled Trials as Topic
PubMed: 11406053
DOI: 10.1002/14651858.CD002985