Tacrolimus and Sirolimus in Objective-C

Creating ECC200 in Objective-C Tacrolimus and Sirolimus

As in cyclosporine, these are two immunomodulating drugs developed for and used by the organ transplant community There has been limited experience with tacrolimus and essentially no published experiences with sirolimus in MG132,735 743 Tacrolimus has

similar toxicities to cyclosporine but has been reported to bene t some who have failed to respond or become refractory to the effects of cyclosporine Sirolimus has a different toxicity pro le than cyclosporine or tacrolimus, particularly in reference to renal function The authors limited and anecdotal experience suggests potential bene t in the setting of declining renal function in patients with severe disease refractory to other agents

The administration of IVIG may result in clinical improvement in some patients with MG95,98,748 754 Some studies have found that IVIG is equivalent to PEX in the treatment of patients,751 while other studies have suggested that PEX is more ef cacious754,755 A similar bene t of PEX over IVIG has been suggested to exist in the anti-MuSK population of patients with MG 37,73,85,86,88,94,132,735 IVIG has not been compared to standard immunosuppressive agents (eg, corticosteroids, azathioprine, and cyclosporine) in a doubleblind prospective fashion Of the two, the authors prefer PEX as opposed to IVIG for the treatment of myasthenic crisis IVIG is reserved for patients with generalized myasthenia in crises who are refractory to PEX or corticosteroids or as an agent to bolster patient strength in anticipation of thymectomy As the lifestyle burden imposed by the duration of IVIG infusions is signi cant, chronic IVIG use is often restricted to those whose disease has failed to respond adequately to corticosteroids, azathioprine, mycophenylate, or cyclosporine In these situations, IVIG (2 g/kg) in two to ve divided doses is given over an equal number of days Repeat infusions are given at monthly intervals for at least 3 months Treatment is subsequently individualized to identify the smallest dose at the longest intervals that provides the desired effect Some patient may need treatment (04 2 g/kg) every week, while others may go several months between IVIG courses All patients should have an IgA level checked prior to treatment, because those with low IgA levels may be at risk of anaphylaxis Patients should also have renal functions checked, especially those with diabetes mellitus, because of a risk of IVIG-induced renal failure Flu-like symptoms, headaches, myalgias, fever, chills, nausea, and vomiting, are common and occur in as many as half the patients receiving IVIG These symptoms can be reduced by premedication with low-dose corticosteroids, acetaminophens, and/or antihistamines and by lowering the infusion rate Rash, aseptic meningitis, and stroke may also complicate IVIG infusions

This agent has not been used as frequently for MG as it has been for autoimmune myopathies (eg, in ammatory myositis) Our experience suggests that methotrexate can be effective Its earlier onset of action provides an advantage over azathioprine It may be initiated orally at 75 mg/week given in three divided doses 12 hours apart The dose is gradually increased by 25 mg each week up to 25 mg/week as necessary The major side effects of methotrexate are alopecia, stomatitis, interstitial lung disease, teratogenicity, oncogenicity, risk of infection, and pulmonary brosis, along with bone marrow, renal, and liver toxicity Doses over 50 mg/week, rarely required or used for MG, require leukovorin rescue All patients are concomitantly treated with folate

There have been a few reports describing the use of cyclophosphamide in the treatment of all forms of acquired MG, including patients with MuSK antibodies744 747 Because of signi cant side effects (ie, gastrointestinal upset, bone marrow toxicity, alopecia, hemorrhagic cystitis, teratogenicity, sterilization, and increased risk of infections and secondary malignancies), most clinicians avoid cyclophosphamide for MG if at all possible Cyclophosphamide may be considered in patients with severe generalized MG refractory to other modes of immunotherapy There are a few general principles that apply to the use of long-term immunomodulatory treatment for MG or any other immune-mediated neuromuscular disease Most of these agents undoubtedly increase the risk of skin cancers Limitation of sun exposure and the liberal use of sun block are encouraged When these agents are used in transplant recipients, Pneumocystis carinii prophylaxis is often recommended The role of P carinii prophylaxis in patients with neuromuscular disease treated with immunomodulating therapy is less well de ned but should be considered, particularly in individuals receiving multiple agents Finally, the natural history of MG is not predictable in most patients It is reasonable, after a year or more of drug-induced remission, to consider a gradual wean from immunomodulating agents with the hope that a protracted remission has been obtained