Current efforts and historical perspectives on classification of idiopathic inflammatory myopathies.

PURPOSE OF REVIEW: The classification of idiopathic inflammatory myopathies is challenging due to the large number of clinical, serological, histopathological and genetic findings, as well as the latest findings and developments in the field of myositis research. The latest official classification criteria are the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies, which have been extensively reviewed in recent years for their applicability, sensitivity and specificity. RECENT FINDINGS: The sensitivity and specificity of the 2017 ACR/EULAR criteria are sometimes performing better, but usually at the same level as the previous criteria. A large number of further suggestions for amendments to the criteria have been made. In particular there is a need to revise the criteria with regard to the addition of new myositis-specific autoantibodies, newly defined subgroups (especially antisynthetase syndrome, immune medicated necrotizing myopathy and overlap myositis) and possibly the addition of further diagnostic procedures (for instance, muscle MRI or PET CT) to improve the accuracy and timeliness of the criteria. SUMMARY: Efforts to optimize the myositis classification criteria have been extensive in recent years and a new global interdisciplinary collaboration of clinicians is currently taking place based on the previous results with the aim of revising the 2017 EULAR/ACR classification criteria.

Performance of the 2017 EULAR/ACR Classification Criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a scoping review.

The 2017 EULAR/ACR classification criteria for adult/juvenile idiopathic inflammatory myopathies (IIM) were established using a data-driven approach by an international group of myositis experts to allow classification of IIM and its major subtypes. Since their publication, the performance of the criteria has been tested in multiple cohorts worldwide and significant limitations have been identified. Moreover, the understanding and classification of IIM have evolved since 2017. This scoping review was undertaken as part of a large international project to revise the EULAR/ACR criteria and aims to i) summarise the evidence from the current literature on the performance characteristics of the 2017 EULAR/ACR classification criteria in various cohorts and IIM subtypes, and ii) delineate the factors that need to be considered in the revision of the classification criteria. A systematic search of Medline (via PubMed), Cumulative Index to Nursing and Allied Health Literature, and conference abstract archives was conducted independently by three investigators for studies on the EULAR/ACR criteria published between October 2017 and January 2023. This scoping review of 19 articles and 13 abstracts revealed overall good performance characteristics of the EULAR/ACR criteria for IIM, yet deficiencies in lack of inclusion of certain IIM subtypes, such as immune mediated necrotising myopathy, amyopathic dermatomyositis, antisynthetase syndrome and overlap myositis. Published modifications that may improve the performance characteristics of the criteria for classification of IIM subtypes were also summarised. The results of this review suggest that a revision of the EULAR/ACR criteria is warranted.

Female sex and overweight are associated with a lower quality of life in patients with myasthenia gravis: a single center cohort study.

BACKGROUND: Myasthenia gravis (MG) affects individuals as a chronic autoimmune disease for many years. Commonly, chronic diseases significantly reduce the patients' quality of life. Aiming to improve the future quality of life in MG, this study assessed the factors impacting quality of life. As gender-specific medicine is becoming increasingly important, this study also focused on understanding gender differences in the outcome of MG. METHODS: The study is a combined monocentric, retrospective and prospective database analysis of patient records based on 2,370 presentations of 165 patients with clinically, serologically and/or electrophysiologically confirmed MG over an observation period of up to 47 years. The data collection included the following parameters: antibody status, disease severity, age, medication use, gender, and disease duration. In addition, a prospective survey was conducted on the quality of life using the Myasthenia gravis-specific 15-item Quality of Life scale (MG-QoL15) and on the activities of daily living using the MG-specific Activities of Daily Living scale (MG-ADL). RESULTS: Of the 165 patients, 85 were male (51.5%) and 80 were female (48.5%). The remaining baseline characteristics (e.g. age and antibody status) were consistent with other myasthenia gravis cohorts. A high body mass index (BMI) (p = 0.005) and a high disease severity (p < 0.001) were significantly associated with lower disease-specific quality of life. Additionally, the quality of life in women with MG was significantly reduced compared to male patients (19.7 vs. 13.0 points in the MG-QoL15, p = 0.024). Gender differences were also observable in terms of the period between initial manifestation and initial diagnosis and women were significantly more impaired in their activities of daily living (MG-ADL) than men (4.8 vs. 3.0 points, p = 0.032). CONCLUSION: Women with MG had significantly poorer disease specific quality of life compared to men as well as patients with a higher BMI. In order to improve the quality of life, gender-specific medicine and further investigation regarding a modification of the quality of life by lowering the BMI are essential and necessary. TRIAL REGISTRATION: Study approval by the Ethics Committee of the University Medical Center Göttingen was granted (number 6/5/18).

Treatment and outcomes in anti-HMG-CoA reductase-associated immune-mediated necrotising myopathy. Comparative analysis of a single-centre cohort and published data.

OBJECTIVES: Anti-hydroxy-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-associated myopathy was recognised as a new form of immune-mediated necrotising myopathy (IMNM) a decade ago. Due to the rarity of the disease, only limited data on clinical manifestations and therapeutic outcomes are available. METHODS: We retrospectively analysed a monocentric cohort of HMGCR-associated IMNM patients treated at the University Medical Centre Göttingen. Clinical, laboratory, and biopsy data, as well as treatment outcomes, were analysed. In addition, a literature search was performed on published HMGCR IMNM cohorts in Medline and Web of Science. RESULTS: We identified nine patients; five were female. The median age was 68 years (47-77). Six were statin-exposed and older than statin-naive patients (71 years [65-77] vs. 51 years [47-67]). All had muscle weakness, seven myalgias. Strength (MRC sum score) was 53/65 (46-61) at baseline and increased to 63/65 (50-65) with therapy. Creatine kinase (CK) levels decreased from a median level of 12837 U/L (range 6346-25011) to 624 U/L (35-1564 U/L). All received glucocorticoids (GC) and at least one immunosuppressive therapy. The literature review identified 26 studies comprising 691 patients. 57.9% were female, 61.3% statin exposed. 95.2% had weakness, 39.1% myalgia. Dysphagia affected 28.8%. 84.9% received GC and a median of 1.5 additional immunosuppressants. Compared to published data, our patients had higher baseline CK values (12837 [6346-25011] vs. 6951 [2539-10500], p<0.001), and we used azathioprine and intravenous immunoglobulins (p<0.001) more frequently but methotrexate and rituximab less frequently (p<0.001). CONCLUSIONS: HMGCR-associated IMNM is a rare subset of myositis. With systemic treatment, patients usually achieve partial or complete remission. Optimal treatment has not been established, but glucocorticoids, azathioprine, and methotrexate are generally effective with or without intravenous immunoglobulins.

Post-discharge adjustment of medication in geriatric patients : A prospective cohort study.

BACKGROUND: Little is known to what extent general practitioners (GP) change hospital discharge medications in older patients. OBJECTIVE: This prospective cohort study aimed to analyze medication changes at the interface between hospital and community in terms of quality, quantity and type of drugs. METHODS: A total of 121 out of 248 consecutively enrolled patients admitted to an acute geriatric hospital unit participated in the study. Medication regimens were recorded at admission and discharge and 4 weeks after hospital discharge the general practitioners in charge were contacted to provide the current medication charts. Changes in the extent of polypharmacy, in the type of drugs using anatomical therapeutic chemical classification (ATC) codes and potentially inappropriate medications (PIM) were analyzed. RESULTS: Medication charts could be obtained for 98 participants in primary care. Only 21% of these patients remained on the original discharge medication. Overall, the average number of medications rose from hospital admission (6.58 SD ± 3.45) to discharge (6.96 SD ± 3.49) and again post-discharge in general practice (7.22 SD ± 3.68). The rates of patients on excessive polypharmacy (≥10 drugs) and on PIM were only temporarily reduced during hospital stay. The GPs stopped anti-infective drugs (ATC-J) and prescribed more antirheumatic drugs (ATC-M). Although no significant net changes occurred in other ATC groups, a substantial number of drugs were interchanged regarding the subgroups. CONCLUSION: The study found that GPs extensively adjusted geriatric discharge medications. Whereas some changes may be necessary due to alterations in patients' state of health, a thorough communication between hospital doctors and GPs may level off different prescribing cultures and contribute to consistency in medication across sectors.

Antibody Therapies in Autoimmune Inflammatory Myopathies: Promising Treatment Options.

Inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM), necrotizing myopathy (NM), antisynthetase syndrome (ASS) and overlap myositis (OM), in short myositis, are rare diseases. All forms of myositis have progressive muscle weakness in common, with each subtype characterized by different autoantibody profiles, histological findings and extramuscular manifestations. Due to better understanding of the pathogenesis of the muscle inflammation in myositis, new molecular pathways for targeted therapy have been discovered. Current therapies aim at different components of the innate or the adaptive immune response. Additionally, non-inflammatory mechanisms in myositis have come into focus as possible treatment targets. The use of therapeutical antibodies in myositis has been examined in various clinical studies, several of them randomized controlled ones: Depletion of B-cells by rituximab has been established as treatment of refractory myositis. IVIG, an antibody therapy in the wider sense, has now been licensed for DM following a recent positive clinical trial. Negative study results were reported in randomized trials with infliximab, sifalimumab and bimagrumab. Studies on basiliximab and eculizumab are currently underway, and are expected to yield results in a couple of years. Despite some promising results of clinical studies with antibody therapy in myositis, further research is crucial to optimize the treatment for this debilitating disease and to find treatment alternatives for treatment-refractory patients.

Update on Myositis Therapy: From Today's Standards to Tomorrow's Possibilities.

Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.

Inflammatory myopathies: shedding light on promising agents and combination therapies in clinical trials.

INTRODUCTION: Due to new insights into the pathogenesis of inflammatory myopathies - in short myositis - and the urgent need for new treatment options in patients who are refractory to standard therapy, multiple novel drugs have been developed and studied in clinical trials. In light of this exciting development, a critical evaluation of the present data is necessary in order to identify the best pathway to future treatment of inflammatory myopathies. AREAS COVERED: This review focuses on the current evidence from clinical trials in myositis and encompasses dermatomyositis, polymyositis, necrotizing myopathy, antisynthetase-syndrome, overlap myositis, and inclusion body myositis. The results of studies on new therapeutic agents are summarized, in particular larger cohort studies and randomized trials from recent years. When such data were not available, earlier and smaller representative studies were included instead. EXPERT OPINION: Current studies in most myositis subtypes have shown positive effects of novel biologicals such as abatacept, sifalimumab, JAK-Inhibitors as well as known agents such as rituximab, but further studies are needed to confirm these observations. In inclusion body myositis, the eagerly awaited recent therapeutic trials have missed their primary endpoints, except for the phase 2 study with rapamycin, which has demonstrated significant improvements in secondary endpoints. Future trials will also need to focus on combination therapies of multiple immunomodulatory agents.

New insights into the treatment of myositis.

The myositis syndromes include polymyositis, dermatomyositis (DM), necrotizing myopathy, inclusion body myositis (IBM), antisynthetase syndrome and overlap syndromes with myositis. These syndromes mostly occur in middle-aged patients, while juvenile DM occurs in children and adolescents. Patients mostly show a subacute weakness and myalgia in the upper and lower limbs, the diagnosis is based upon these clinical findings in combination with muscle biopsy results and specific serum autoantibodies. In recent years, research achieved a better understanding about the molecular mechanism underlying the myositis syndromes, as well as disease progress and extramuscular organ manifestations, such as interstitial lung disease and association with neoplasias. Treatment mainly consists of glucocorticosteroids and immunosuppressants. IBM is usually refractory to treatments. This review provides an overview of the current standards of treatment and new treatment options like monoclonal antibodies and new molecular therapies and their first results from clinical trials.

Myalgia in myositis and myopathies.

Myalgia is a common symptom of various neuromuscular disorders: myalgia occurs in metabolic muscle diseases, inflammatory muscle diseases, dystrophic myopathies and myotonic muscle disorders. Myalgia leads to a significantly reduced quality of life. Other muscular symptoms that are present along with myalgia often provide the clue towards a diagnosis and include weakness, cramps and myotonia as well as the type of pain. In addition, extramuscular symptoms like an erythema in dermatomyositis can lead to the correct diagnosis. Basic diagnostic workup includes a detailed medical history, full neurologic assessment, laboratory tests, EMG and nerve conduction studies. Muscle imaging, genetic testing and muscle biopsy may be required to make a diagnosis. Whenever possible, treatment should aim to improve or correct the underlying cause for myalgia such as inflammation or hypothyroidism. Symptomatic therapy includes different avenues: Myotonia can be treated with mexiletine. Carbamazepine or phenytoin can be used in myotonic syndromes, particularly with muscle cramps. Pregabalin, gabapentin, or amitriptyline can be tried in conditions with myalgic pain. This review summarizes the symptoms, diagnostic strategies, and therapeutic approach in neuromuscular disorders that present with myalgia.