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      Myasthenia gravis exacerbation after discontinuing mycophenolate : A single-center cohort study

      , , ,
      Neurology
      Ovid Technologies (Wolters Kluwer Health)

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          Abstract

          <div class="section"> <a class="named-anchor" id="d9784823e919"> <!-- named anchor --> </a> <h5 class="section-title" id="d9784823e920">Objective:</h5> <p id="d9784823e922">To determine whether discontinuation or marked reduction of mycophenolate mofetil (MMF) in patients with myasthenia gravis (MG) causes MG exacerbations. </p> </div><div class="section"> <a class="named-anchor" id="d9784823e924"> <!-- named anchor --> </a> <h5 class="section-title" id="d9784823e925">Methods:</h5> <p id="d9784823e927">We identified 88 patients with MG who took MMF during the 5-year period 2007–2011 at our MG clinic. We then performed detailed chart reviews and recorded all MG exacerbations and their relationship to MMF and other treatment changes. We also recorded demographic data and disease characteristics (including antibody status and Myasthenia Gravis Foundation of America status). </p> </div><div class="section"> <a class="named-anchor" id="d9784823e929"> <!-- named anchor --> </a> <h5 class="section-title" id="d9784823e930">Results:</h5> <p id="d9784823e932">There were 14 patients who had an MG exacerbation during the study period. Of these, 13 had discontinued MMF therapy, with a median time until exacerbation of 16 weeks after discontinuation (9 patients) or marked dose reduction (4 patients) of MMF therapy (exacerbation in the absence of change in any other component of the immunosuppressive regimen). Using the cluster option in a Cox regression analysis, the MMF coefficient was −5.32, with a standard error of 1.05 and a <i>p</i> value of 0.0002, corresponding to an estimated hazard ratio of 204. </p> </div><div class="section"> <a class="named-anchor" id="d9784823e937"> <!-- named anchor --> </a> <h5 class="section-title" id="d9784823e938">Conclusions:</h5> <p id="d9784823e940">This retrospective cohort study suggests that discontinuation/marked reduction of MMF therapy may increase the risk of MG exacerbation many fold, supporting the hypothesis that MMF plays a role in the maintenance of MG remission/minimal manifestation status. </p> </div><div class="section"> <a class="named-anchor" id="d9784823e942"> <!-- named anchor --> </a> <h5 class="section-title" id="d9784823e943">Classification of evidence:</h5> <p id="d9784823e945">This study provides Class IV evidence that in patients with MG taking MMF, discontinuation or marked reduction of MMF causes MG exacerbation. </p> </div>

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          Most cited references10

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          An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis.

          This prospective, randomized, double-blind, placebo-controlled, phase III trial assessed the efficacy, safety, and tolerability of mycophenolate mofetil (MMF) as a steroid-sparing agent in patients with myasthenia gravis (MG). Patients with acetylcholine receptor antibody-positive class II-IVa MG (MG Foundation of America [MGFA] criteria) taking corticosteroids for at least 4 weeks were randomized to MMF (2 g/day) or placebo for 36 weeks. The primary endpoint was a composite measure defined as achievement of minimal manifestations or pharmacologic remission (MGFA post-intervention status), with reduction of corticosteroid dose on a set schedule. Secondary endpoints included disease severity, quality-of-life scores, and safety. A total of 44% of MMF-treated (n = 88) and 39% of placebo-receiving (n = 88) patients achieved the primary endpoint (p = 0.541). Improvements in mean quantitative MG, MG activities of daily living, and 36-item Short-Form health survey scores were similar in both groups. Numbers of adverse events were similar in both groups. The most commonly reported adverse events in the MMF-treated group were headache (12.5%) and worsening of MG (11.4%), and in the placebo group, worsening of MG (20.5%) and diarrhea (10.2%). Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.
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            A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis.

            (2008)
            To test the hypothesis that mycophenolate mofetil (MMF) with prednisone provides better control of myasthenic weakness than prednisone alone in the initial management of generalized myasthenia gravis (MG). Eighty immunosuppression naïve subjects with mild to moderate generalized, acetylcholine receptor positive MG at 13 centers were randomized to 2.5 g/day MMF plus 20 mg/day prednisone (n = 41) or placebo plus 20 mg/day prednisone (n = 39) and followed in a double-blind fashion for 12 weeks. Subjects over 18 years of age were included if judged to be candidates for immunosuppression; excluded were those with thymoma or severe oropharyngeal or respiratory muscle weakness. The primary measure of efficacy was change in the quantitative MG (QMG) score from baseline to week 12. Study completers could take open-label MMF for an additional 24 weeks, while prednisone was reduced to the minimally effective dosage. The mean change in QMG score was similar in the treated (-4.4 +/- 5.1) and placebo (-3.6 +/- 5.0) groups (p = 0.71). The dosage of prednisone was reduced by a similar amount in both groups during the open-label phase. Subjects tolerated the study drug well, without unexpected adverse events. This study demonstrated no benefit of mycophenolate mofetil (MMF) with 20 mg/day prednisone compared to 20 mg/day of prednisone alone after 12 weeks. This may be due to greater than predicted benefit from the prednisone dosage used, the short duration of the study, or the absence of any benefit of MMF in this population of patients with myasthenia gravis.
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              Mycophenolate mofetil in AChR-antibody-positive myasthenia gravis: outcomes in 102 patients.

              Two recent randomized, controlled trials failed to demonstrate a benefit of mycophenolate mofetil (MMF) over prednisone in the treatment of myasthenia gravis (MG). We reviewed our experience with MMF in MG to determine whether these trials may have been unsuccessful because of their short duration and the unpredicted benefit of prednisone. We reviewed outcomes and prednisone dosage for all our acetylcholine-receptor (AChR)-antibody positive MG patients treated with MMF alone or with prednisone for at least 3 months. The percentage of patients with a desirable outcome (MG-specific Manual Muscle Test score 24 months had a desirable outcome. Prednisone dose decreased after 12 months; after 25 months, 54.5% of patients took no prednisone and 75% took <7.5 mg/day. This retrospective analysis provides class IV evidence that MMF begins to improve AChR-positive MG after 6 months, both with prednisone and as monotherapy.
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                Author and article information

                Journal
                Neurology
                Neurology
                Ovid Technologies (Wolters Kluwer Health)
                0028-3878
                1526-632X
                March 21 2016
                March 22 2016
                March 22 2016
                February 05 2016
                : 86
                : 12
                : 1159-1163
                Article
                10.1212/WNL.0000000000002405
                4820129
                26850977
                f824e87b-a26c-44b3-a6f7-39fca17dd2eb
                © 2016
                History

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