Neuromuscular Junction Disorders
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Azathioprine (AZA): Interferes with B- and T-cell proliferation by inhibiting purine synthesis.Used for corticosteroid sparing.Full benefit of treatment may not be reached until >1 year.Initiated at 50 mg daily or twice daily and increased by 50 mg per week until maintenance dose of 2–3 mg/kg/day.Major side effects are hepatotoxicity and leukopenia. Therefore, liver function tests and white blood cell count should be monitored. A flu-like reaction may appear a few weeks after initiation (or in some cases much later), which may be severe and associated with neutropenia. AZA must be promptly discontinued.Risk for certain malignancies, particularly hematopoietic malignancies, may increase in long-term treatment with AZA.
Other Immunosuppressive Agents in Vitiligo
Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan in Comprehensive Textbook on Vitiligo, 2020
Azathioprine is an immunosuppressive agent which is widely used in autoimmune disorders. It has a good safety profile and is also more cost effective. Its use in vitiligo is limited. It has been tried as combination therapy with oral PUVA and compared with oral PUVA therapy alone. Azathioprine was given at a dose of 0.6–0.75 mg/kg (max dose 50 mg per dose). After a follow-up for 4 months, 58.4% body surface repigmentation was seen in the azathioprine and PUVA therapy combination group, while only 28.4% repigmentation was seen in the PUVA therapy only group. Repigmentation of the acral areas was better in the azathioprine only group while perifollicular repigmentation was earlier in the azathioprine and PUVA combination group. Two patients developed gastric upset while on azathioprine. This was the only side effect seen [11].
Pregnancy in SLE
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
Treatment of lupus glomerulonephritis during pregnancy differs in some details from its treatment in a nonpregnant patient. Because of increased drug metabolism during pregnancy higher doses of prednisone may be necessary. Because of drug effects on the fetus, the usual pharmacopoeia is limited. Prednisone does not cross the placenta and may be used in full doses.49,50 Fluorinated corticosteroids (dexamethasone, betamethasone) do cross the placenta and should not be used51 as they may affect the baby’s immunologic responses.52 The effect of bolus intravenous “pulse” methylprednisolone on the fetus is unknown; it does reach the fetus.53 It should not be used in pregnant patients if other options are available. Although many normal children have been born of mothers taking azathioprine, it is appropriate to be conservative about use of this drug in pregnancy.54-58 Cyclophosphamide is highly teratogenic; it is contraindicated both orally and intravenously in pregnant women.
Clinical pearls and promising therapies in myositis
Published in Expert Review of Clinical Immunology, 2023
Caoilfhionn M. Connolly, Julie J. Paik
Systemic glucocorticoids with concurrent steroid-sparing agent represent the first-line approach for ASyS. The choice of steroid-sparing agent is determined by the severity of lung involvement, as well as other disease manifestations. MMF is used preferentially in patients with moderate-to-severe ILD as the first-line agent [20]. Azathioprine is an alternative agent with demonstrated efficacy [21]. Calcineurin inhibitors are also commonly used in patients with ASyS-ILD although some clinicians reserve this for progressive/refractory cases. A small retrospective study demonstrated stability/improvement in forced vital capacity (FVC) among 13/15 patients with ASyS following treatment with CNI [75]. All patients should be encouraged to engage in daily aerobic exercise, referred to pulmonary rehabilitation where possible, and should be educated on the importance of weight optimization, infection prevention through vaccination as well as smoking cessation (where applicable).
Biological therapies in patients with liver disease: are they really lifesavers?
Published in Expert Opinion on Biological Therapy, 2022
Giovanni Vitale, Stefano Gitto, Claudia Campani, Laura Turco, Anna Baldan, Fabio Marra, Maria Cristina Morelli
In other case reports and case series, rituximab was able to induce complete remission: two children with refractory autoimmune hepatitis received rituximab at the dosage of 375 mg/m2 weekly for four doses while persistent normalization of transaminases was maintained with small doses of prednisone and with azathioprine (1 mg/kg/day); to obtain remission, rituximab was administered at same dose every 4 months and every 6 months in each patient, respectively [27]. In another case series, six patients with AIH resistant to azathioprine and prednisone were treated with two infusions of 1000 mg of rituximab 2 weeks apart: patients remained on stable doses of azathioprine and prednisone for at least 3 months before rituximab infusion. Prednisone was administrated at the same doses throughout the 3-month follow-up period. The dose of azathioprine was stable for at least 3 months and was unchanged in the follow-up period. After week 24 of follow-up, aspartate aminotransferase and immunoglobulin G levels had significantly improved, and the prednisone was stopped in three of four subjects, without flaring after steroid withdrawal. Finally, inflammation grade at liver histology improved in all four subjects at week 48 [28].
An update on the pharmacological management of autoimmune hepatitis
Published in Expert Opinion on Pharmacotherapy, 2021
Yooyun Chung, Mussarat N Rahim, Jonathon J Graham, Yoh Zen, Michael A Heneghan
At least 10–20% of the patients will have insufficient response or intolerance to first-line therapy. Insufficient response is defined as incomplete biochemical remission after 6 months of treatment. In the first instance, measuring the azathioprine metabolites, 6-TGN and 6-MMP, will guide dose optimization or adjunctive therapy with allopurinol. Low 6-TGN and low 6-MMP levels can be ameliorated by increasing the azathioprine dose. Low 6-TGN and high 6-MMP levels can be optimized with use of allopurinol (100 mg/day) to reduce 6-MMP production. This strategy requires the azathioprine dose to be reduced by 75% to prevent toxicity from increased 6-TGN production [31]. Low 6-TGN and 6-MMP levels despite dose adjustments may indicate noncompliance to thiopurine treatment. Azathioprine side effects include gastrointestinal symptoms. If a patient is intolerant of azathioprine, changing to MP is a reasonable first step as it is as effective as azathioprine and can be better tolerated in the context of gastrointestinal side effects [32].
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