The Impact of Autoantibody Profiles on Treatment Response in Idiopathic Inflammatory Myopathies

213th ENMC International Workshop: Outcome measures and clinical trial readiness in idiopathic inflammatory myopathies, Heemskerk, The Netherlands, 18–20 September 2015

Background:Idiopathic inflammatory myopathies (IIM) are a heterogenous disease group. Due to its heterogenicity, treatment of IIM is not simple, as it involves a holistic strategy taking care of the various...

To determine whether rituximab (RTX) is effective in 'treatment-naïve' idiopathic inflammatory myopathies (IIM), and whether there could be differential treatment responses between 'treatment-naïve' and treatment 'refractory' IIM. Data were obtained from a prospectively maintained database comprising patients with IIM treated with RTX. Patient details were obtained at baseline, 3- and 6-months intervals, and at subsequent follow-up visits. Treatment response was categorized as improved, worsening or stable based on Manual Muscle Testing 8 (MMT8) scores, patient global and physician global improvement for skin and joint symptoms improvement, and spirometry at 6 months. The time to clinical improvement and remission were noted and survival analysis curves were constructed. Sixty patients with IIM (including 18 with anti-signal recognition particle myopathy) were included, of whom 33 who received RTX were treatment naïve. The remaining 27 were started on RTX for refractory myopathy. The mean age was 39 years (s.d. 12.58) in the 'treatment-naïve' group and 43 years (s.d. 12.12) in the 'refractory' group. At 6 months of follow-up, 48/55 (87%) patients showed response, 31/31 (100%) in 'treatment-naïve' and 17/24 (70%) in 'refractory' cases, P = 0.006*. In the refractory group, seven (29%) had stable disease. The mean changes in MMT8 were significantly more in the 'treatment-naïve' group [13.41 (s.d. 7.31)] compared with 'refractory' IIM [8.33 (s.d. 7.92)] (P = 0.017*). The majority of patients were able to reduce the dose to <5 mg/day before 6 months. No major adverse events were reported over the median follow-up of 24 (interquartile range 36) months. RTX is effective and safe across the spectrum of IIM. Early use in disease is associated with better outcomes.

In our study, CAM in ASS were more prevalent compared to literature data. CAM were independently associated with age, fever and low CPK levels. CAM patients had higher mortality. Careful...

Idiopathic inflammatory myopathies (IIM) are a group of rare autoimmune diseases characterized by muscle weakness. IIMs are characterized by heterogeneity of manifestations and include several variants, each of which has peculiarities related to pathogenesis and autoantibody profile, clinical presentation, prognosis and response to therapy. In this context, the importance of early diagnosis and correct interpretation of clinical, laboratory and instrumental data is becoming increasingly important in order to recognize the phenotype of IIM in time.An important tool for the assessment of muscle damage is magnetic resonance imaging (MRI), which provides detailed anatomical and topographical information about muscles and adjacent soft tissues. The characteristics of the MRI of the muscles in different IIM phenotypes have not been sufficiently investigated.Objective: to evaluate and compare magnetic resonance (MR) signs of muscle damage in patients with dermatomyositis (DM) and sporadic inclusion body myositis (SIBM).Material and methods. The prospective study included 30 patients with IIM, including 15 with DM and 15 with SIBM. The diagnosis was based on the 2017 EULAR/ACR classification criteria. MRI of the thigh and calf muscles was performed using a Philips Multiva 1.5 TESLA (Philips, the Netherlands), and the intensity of muscle tissue edema and fatty replacement were assessed using a 4-point scale, as well as the total score and aggregated score by muscle groups according to the topographic and anatomical structure.Results and discussion. The total edema score was statistically significantly higher in DM than in SIBM (p&lt;0.001). In contrast, the total fatty replacement score and the aggregated score of all thigh muscle groups (anterior, p&gt;&lt;0.001; posterior, p=0.03; medial, p=0.02) were significantly higher in SIBM than in DM. In contrast to DM, all patients with SIBM had two additional MR signs: "distal gradient" and the "undulating fascia" symptom. No statistically significant differences were found between the compared IIM variants in the assessment of the total and aggregated edema score of calf muscle. At the same time, when assessing fatty replacement, the total and aggregated score in the anterior, posterior and lateral muscle groups were significantly higher in SIBM than in DM. Thus, the leading MR sign in DM was edema mainly in the anteromedial and posterior muscle groups of the thighs (due to the semitendinosus and semimembranosus muscles) and the anteroposterior calf muscle group. In SIBM, fatty replacement predominates in the anterior muscle group of the thighs and in the anterolateral and posterior calf muscle groups. Conclusion. The MR features of two clinically distinct variants of IIM, DM and SIBM are demonstrated, which reflect the heterogeneity of this disease group. MRI may be an informative method to identify MR patterns within the IIM group. Keywords: magnetic resonance imaging; diagnostics; inflammatory myopathies&gt; &lt; 0.001). In contrast, the total fatty replacement score and the aggregated score of all thigh muscle groups (anterior, p &lt; 0.001; posterior, p=0.03; medial, p=0.02) were significantly higher in SIBM than in DM. In contrast to DM, all patients with SIBM had two additional MR signs: "distal gradient" and the "undulating fascia" symptom. No statistically significant differences were found between the compared IIM variants in the assessment of the total and aggregated edema score of calf muscle. At the same time, when assessing fatty replacement, the total and aggregated score in the anterior, posterior and lateral muscle groups were significantly higher in SIBM than in DM. Thus, the leading MR sign in DM was edema mainly in the anteromedial and posterior muscle groups of the thighs (due to the semitendinosus and semimembranosus muscles) and the anteroposterior calf muscle group. In SIBM, fatty replacement predominates in the anterior muscle group of the thighs and in the anterolateral and posterior calf muscle groups.Conclusion. The MR features of two clinically distinct variants of IIM, DM and SIBM are demonstrated, which reflect the heterogeneity of this disease group. MRI may be an informative method to identify MR patterns within the IIM group.

PNEUMONIA MASQUERADING AS ANTI-SYNTHETASE SYNDROME

Idiopathic inflammatory myopathies (IIMs) are a group of acquired muscle diseases with muscle inflammation, weakness, and other extra-muscular manifestations. IIMs can significantly impact the quality of life, and management of IIMs often requires a multi-disciplinary approach. Imaging biomarkers have become an integral part of the management of IIMs. Magnetic resonance imaging (MRI), muscle ultrasound, electrical impedance myography (EIM), and positron emission tomography (PET) are the most widely used imaging technologies in IIMs. They can help make the diagnosis and assess the burden of muscle damage and treatment response. MRI is the most widely used imaging biomarker of IIMs and can assess a large volume of muscle tissue but is limited by availability and cost. Muscle ultrasound and EIM are easy to administer and can even be performed in the clinical setting, but they need further validation. These technologies may complement muscle strength testing and laboratory studies and provide an objective assessment of muscle health in IIMs. Furthermore, this is a rapidly progressing field, and new advances are going to equip care providers with a better objective assessment of IIMS and eventually improve patient management. This review discusses the current state and future direction of imaging biomarkers in IIMs.

The idiopathic inflammatory myopathies (IIMs) are chronic disorders characterized by inflammation in skeletal muscle but also in other organs such as the skin, lungs, joints, gastrointestinal tract, and heart. The effect of immunosuppressive treatment varies between individual patients and between organ manifestations within the same individual. Many patients respond poorly to first-line treatment with glucocorticoids and other immunosuppressive agents such as methotrexate or azathioprine, with symptoms persisting in the muscles, skin, and lungs, leading to refractory disease. Management of refractory IIM is a clinical challenge, and a systematic approach is proposed to better understand the lack of treatment response, in order to guide disease management. The first step in the management of refractory IIM is to recognize whether remaining symptoms are caused by persistent inflammation in the affected tissue or whether the symptoms may be attributable to damage preceding inflammation. Thus, a second diagnostic examination is recommended. Second, in particular for patients with remaining muscle weakness, it is important to ascertain whether the diagnosis of myositis is correct or whether another underlying muscle disorder could explain the symptoms. Third, with confirmation of remaining inflammation in the tissues, a strategy to change treatment needs to be undertaken. Few controlled trials are available to guide our treatment strategies. Furthermore, different subgroups of patients may benefit from different therapies, and different organ manifestations may respond to different therapies. In this context, subgrouping of patients with IIM based on autoantibody profile may be helpful, as there are emerging data from open studies and case series to support the notion of a varying treatment response in different autoantibody-defined subgroups of IIM patients.

BackgroundLittle is known about mortality in idiopathic inflammatory myopathies (IIM) compared to the general population, especially the risk development since diagnosis. In a recently published study, the 5-, and 10-year...

ObjectiveTo develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.MethodsCandidate variables were assembled from published criteria and expert opinion using consensus...

Idiopathic inflammatory myopathies (IIM), also known as myositis, are a heterogeneous group of autoimmune disorders with varying clinical manifestations, treatment responses and prognoses. Muscle weakness is usually the classical clinical manifestation but other organs can be affected, including the skin, joints, lungs, heart and gastrointestinal tract, and they can even result in the predominant manifestations, supporting that IIM are systemic inflammatory disorders. Different myositis-specific auto-antibodies have been identified and, on the basis of clinical, histopathological and serological features, IIM can be classified into several subgroups - dermatomyositis (including amyopathic dermatomyositis), antisynthetase syndrome, immune-mediated necrotizing myopathy, inclusion body myositis, polymyositis and overlap myositis. The prognoses, treatment responses and organ manifestations vary among these groups, implicating different pathophysiological mechanisms in each subtype. A deeper understanding of the molecular pathways underlying the pathogenesis and identifying the auto-antigens of the immune reactions in these subgroups is crucial to improving outcomes. New, more homogeneous subgroups defined by auto-antibodies may help define disease mechanisms and will also be important in future clinical trials for the development of targeted therapies and in identifying biomarkers to guide treatment decisions for the individual patient.

BackgroundThere are uncertainties regarding the occurrence of idiopathic inflammatory myopathies (IIM) after infection by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus2(CoV2) or in recipients of Coronavirus disease-19 (Covid-19) vaccines.ObjectivesHerein, the main objective...

BackgroundVarious inflammatory markers have been suggested for detecting idiopathic inflammatory myopathies (IIMs); however, their diagnostic utility remains inconclusive.ObjectivesMuscle tissues from patients diagnosed with IIMs from January 2001 to March 2017...

G.P.65 Epidemiological study of malignancy-associated myositis in Japan

Idiopathic inflammatory myopathies (IIM) are a group of chronic rheumatic diseases that can affect multiple systems; the risk of ischemic stroke in patients with IIM remains controversial. We aimed to systematically evaluate the risk of ischemic stroke in IIMs. The PubMed, Embase, and Cochrane library were searched for relevant studies. Pooled relative risk (RR) with a 95% confidence interval (CI) was calculated as effect size to evaluate the risk of ischemic stroke in patients with IIM. Random effects model was chosen when I2 > 50%. We pooled all studies in a first total analysis to assess the risk of ischemic stroke in IIM. Subgroup analyses were conducted based on the subtypes of IIM (dermatomyositis) and country. Sensitivity analysis was performed to identify the heterogeneity sources. A total of 6 studies with 5,114 IIM cases and 14,516,099 controls were included, and the results demonstrated that IIMs were associated with an increased risk of ischemic stroke (RR = 2.41, 95% CI: 1.31, 4.45). Subgroup analysis indicated that patients with dermatomyositis (DM) had a 49% excess risk of ischemic stroke than controls; Asian patients with IIM had an increased risk of ischemic stroke, although not for American patients. IIMs, especially patients with DM, are associated with an increased risk of ischemic stroke. Appropriate intervention may be taken into account for patients with IIM, especially when accompanied by other traditional risk factors of ischemic stroke. Key Points • This study evaluated the risk of ischemic stroke in patients with IIMs. • Generally, IIMs are associated with an increased risk of ischemic stroke. • Patients with DM had a 49% excess risk of ischemic stroke than controls. • Subgroup analysis showed that Asian patients with IIMs were at increased risk of ischemic stroke, but not Americans.