4/16/2018. Demystifying weakness: how to approach refractory myositis. Objectives. Disclosures. Off-label uses for medications will be discussed
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1 Demystifying weakness: how to approach refractory myositis Jemima Albayda, MD Assistant Professor Johns Hopkins Myositis center Disclosures Off-label uses for medications will be discussed Objectives To develop the approach for evaluation of myositis and its mimics Describe the management challenges in refractory myositis To enumerate new treatments for myositis 1
2 Use of Copyrighted Material Original or modified figures and tables from studies and articles are included in this talk with references provided This information is intended solely for use in an educational lecture setting Further distribution or use in other settings is strictly prohibited Framework for assessment Does the patient have myositis? If they have myositis, what organs are involved and active? What treatments have been tried/can be used? 2017 EULAR/ACR classification criteria for IIM Aim was to define minimum essential, easily available clinical and laboratory features to: 1) Distinguish IIM from mimics 2) Distinguish major subgroups of IIM Uses a weighted score; with and without muscle biopsy Total score corresponds to probability of having IIM Definite IIM: probability 90%, 7.5 ( 8.7 with muscle biopsy) Minimum score of 5.5; 6.7 with muscle bx to classify as IIM 2
3 Lundberg et al. Arthritis Rheumatol Dec;69(12): Does the patient have myositis? Typical skin rashes Subacute proximal weakness Elevated muscle enzymes EMG myopathic changes MRI evidence of acute edema Myositis specific antibody Other signs of immune-mediated phenomena Response to medications Compatible muscle biopsy Features suggestive of nonautoimmune myopathy Positive family history of muscle weakness Slow progressive evolution of weakness over months to years Presence of facial or extraocular muscle weakness Scapular winging Presence of distal weakness greater than or equal to proximal weakness Presence of asymmetric weakness Lack of myositis autoantibodies Lack of systemic manifestations of autoimmune disorders Curr Rheumatol Rep Oct;17(10):63 3
4 Major mimics to consider Metabolic myopathies McArdle s, Pompe s Muscular dystrophies FSHD, dysferlinopathy Mitochondrial myopathies Endocrine myopathies Thyroid, parathyroid, DM Curr Rheumatol Rep Oct;17(10):63 Considerations for treatment of IIM Specific organ involvement Severity of presentation Known antibody Distinction of activity versus damage Therapeutic Strategies Use medications that target involved organs Treatment with steroids is variable Consider the severity of presentation and how quickly medications take effect Consider comorbidities If cannot taper steroids readily, should optimize background therapy 4
5 TREATMENT OPTIONS Methotrexate 20-25mg/wk Azathioprine 2mg/kg/day Mycophenolate mofetil 2-3g daily IVIG- 2g/kg divided over 3-5 days every 4 weeks Rituximab- 1g on day 0 and 1 g on day 14 *Hydroxychloroquine TREATMENT OPTIONS Tacrolimus Cyclosporine Cyclophosphamide TNF inhibitors Plasmapheresis Acthar Recent Studies for Refractory disease Infliximab- 2/6 patients achieved DOI Abatacept- 8/19 patients achieved DOI ACTH gel- 7/10 patients achieved DOI Semin Arthritis Rheum Oct 16. pii: S (17) Ann Rheum Dis Jan;77(1): Ann Rheum Dis Dec 13. pii:annrheumdis
6 Treatments being investigated Tofacitinib Abatacept Tocilizumab Anabasum- a Cannabinoid receptor type 2 agonist Some practical tips If with ILD, we generally start with azathioprine or mycophenolate When with cancer, Rituximab and IVIG are safest Aside from steroids, IVIG works fastest Must use therapeutic doses of medications and allow time to take effect Often need combined treatments: methotrexate+azathioprine; rituximab + methotrexate; IVIG and rituximab Treatment challenge: Statin-induced myositis Stop the statin once confirmed Steroids usually started, together with another immunosuppressant Steroids can be avoided if with other comorbidities If mild, can use oral immunosuppression If very weak, we usually start IVIG Rituximab is also an option 6
7 Case Example 62 year old man presented with chronic muscle weakness of over ten years duration, treated with steroids at one time with improvement. 4/5 strength in the arm abductors and 5/5 strength elsewhere There was mild scapular winging and abdominal laxity EMG showed a mild irritable myopathy with early polyneuropathy with predominantly axonal features. Biopsy of the deltoid showed degenerating and regenerating fibers CPK was 482 Case Example 62 year old man presented with chronic muscle weakness of over ten years duration, treated with steroids at one time with improvement. 4/5 strength in the arm abductors and 5/5 strength elsewhere There was mild scapular winging and abdominal laxity EMG showed a mild irritable myopathy with early polyneuropathy with predominantly axonal features. Biopsy of the deltoid showed degenerating and regenerating fibers CPK was 482 FSHD as well as myotonic dystrophy were considered and ruled out by genetic testing. The myositis panel was negative for known antibodies. Case Example He was then treated with steroids However on follow-up, he had symptoms of heart failure with a nadir ejection fraction of 20-25%, findings of cardiomyopathy, and atrial and ventricular arrhythmias. endomyocardial biopsy showing a single foci of perivascular lymphocytes consistent with myocarditis. Azathioprine added, and eventually Rituximab THIS PATIENT HAD ANTIMITOCHONDRIAL AB ASSOCIATED MYOSITIS 7
8 Conclusions Treatment of myositis is challenging given lack of consensus guidelines and heterogeneity of disease Use of immunosuppressive/immunomodulatory agents is mostly guided by organ involvement and severity Many agents are in use and beneficial in myositis Exercise is integral part of treatment Questions? Thank you for your attention Johns Hopkins Myositis Center 8
9 References Aggarwal R, et al. Efficacy and safety of adrenocorticotropic hormone gel in refractory dermatomyositis and polymyositis. Ann Rheum Dis Dec 13. pii:annrheumdis Lundberg et al EULAR/ACR Classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Arthritis Rheumatol Dec;69(12): Michelle EH, Mammen AM. Myositis Mimics. Curr Rheumatol Rep Oct; 17(10)63. Mammen AM. Which nonautoimmune myopathies are most frequently misdiagnosed as myositis? Curr Opin Rheumatol 2017, 29: Schiffenbauer A, et al. A randomized, double-blind, placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis. Semin Arthritis Rheum Oct 16. pii:s (17) Tjarnlund A, et al. Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase Iib treatment delayed-start trial. Ann Rheum Dis Jan;77(1):
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