16 – 18 Most of these patients were AChR positive and had refractory disease, which may account for the less impressive effect of rituximab.
#TABULATED STATISTICS MINITAB EXPRESS SERIES#
A systematic review and meta-analysis of case reports and case series have shown that rituximab is effective for MG patients refractory to immune therapies. Rituximab is a genetically engineered mouse/human IgG1-kappa chimeric monoclonal antibody directed against CD20 surface antigens on B-cells. Rituximab has been used off-label as an effective treatment for MG refractory to other immune therapies. 14, 15 This has led to a search for alternative therapies that can overcome these limitations. 5 Overall, the conventional treatment options for MG have many associated side effects and, in addition, resistance to treatment is reported in 10 %to 15% of patients. It also carries the risk of infection at the vascular access site and hypotension during treatment. It is also inconvenient, uncomfortable, cumbersome, and needs specific equipment and a specialized team. TPE is less expensive than IVIg but is still beyond the resources of many patients in developing countries. 12, 13 IVIg is prohibitively expensive for most patients in developing countries and the effect lasts only for a few weeks. 5, 13 Mycophenolate is known to be associated with leucopenia and an increased risk of infections. Azathioprine has the potential to cause bone marrow suppression and liver dysfunction in certain patients. 12, 13 Immunomodulators like azathioprine or mycophenolate take 3 to 4 months or longer to produce clinical improvement.
The long-term side effects of steroids include hyperglycemia, hypertension, hypokalemia, acneiform eruptions, cushingoid features, cataract, avascular necrosis, gastric ulcers, and opportunistic infections like tuberculosis. Steroids, though effective, have the potential to worsen myasthenic symptoms and precipitate MC, especially at higher doses, within the first 2 to 3 weeks of the initiation of therapy. Immunomodulation in MG is difficult as there are several challenges associated with the existing immunosuppressive treatments. Treatment of refractory MG is a challenge and often requires newer agents like rituximab or eculizumab. 9 Refractory MG patients have more frequent clinical exacerbations, more often need rescue treatments with IVIg or TPE and escalation of immunosuppressive drugs and are more vulnerable to side effects. A subgroup of patients, estimated to be about 10% to 20%, do not respond adequately to conventional immunosuppressants, develop adverse events or require continous treatment with IVIg or TPE and are termed refractory. 8 Intravenous immunoglobulin (IVIg) or therapeutic plasma exchange (TPE) is used for acute treatment of MC and also for moderate to severe worsening of myasthenia gravis. 3 – 7 Approximately 15% to 20% patients with MG experience at least 1 myasthenic crisis (MC) episode in their life. 1, 2 It is treated symptomatically with acetylcholinesterase inhibitors while the autoimmune attack is treated with conventional immunosuppressants like steroids, azathioprine, mycophenolate, cyclosporine, tacrolimus, and methotrexate. It is caused by antibody mediated attacks on the nicotinic acetylcholine receptors (AChR), muscle specific tyrosine kinase (MuSK), and various other novel targets like anti-lipoprotein-related protein 4 (LRP4). Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission.
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