Since previous studies showed an association of a shorter time to diagnosis with better remission, additional studies are needed to investigate if faster and more aggressive treatment approaches are beneficial in certain myasthenia gravis subgroups. an unmet need for new treatment options. Keywords: Myasthenia gravis, Outcome, Refractory disease, Treatment Introduction Myasthenia gravis is an autoimmune disease of the neuromuscular junction with a prevalence of around 16 per 100,000 [1]. Patients are grouped according to the age at onset, presence of a specific antibody, thymus pathology, and distribution of symptoms [2]. The majority of patients (approximately 80%) have antibodies against the nicotinic acetylcholine receptor (AChR), while in a small subset of patients Rabbit Polyclonal to GPR42 antibodies against muscle-specific receptor tyrosine SB269652 kinase (MuSK), lipoprotein-related protein 4 (LRP4) or other postsynaptic structures of the neuromuscular junction are detected. In about 5% of patients, no antibodies are found. Additionally, paraneoplastic disease can occur in patients with thymoma that leads to generalized thymoma-associated myasthenia gravis with the detection of AChR-antibodies in nearly all patients [3, 4]. The natural, untreated course of myasthenia gravis has been associated with a high mortality and a persistence of symptoms in most patients [5, 6], but the introduction of immunosuppressive treatments, thymectomy in selected patients, modern intensive care medicine as well as the availability of rescue treatments such as intravenous immunoglobulins (IVIG), plasma exchange therapy (PLEX) or immunoadsorption (IA) has greatly improved the outcome across all subgroups of patients [7]. However, approximately 10C15% of patients still show a poor response to available standard treatments and consequently continue to suffer from disabling symptoms. They also experience frequent disease exacerbations leading to a reduced quality of life and frequent admissions to hospitals and emergency departments [8C11]. In addition, the necessary treatment with high-dose immunosuppressive drugs is often associated with side effects, which negatively affects patients quality of life. So far, only a few studies have specifically addressed the characteristics of treatment-resistance myasthenia gravis patients [12C14]. It is also an open question which factors predispose patients to a refractory disease course with some observations suggesting an early onset, female gender, an association with thymoma or the presence of MuSK-antibodies as risk factors [13, 14]. Given the unmet clinical needs in treatment-refractory patients, a further characterization and definition of this subgroup is clearly warranted to recognize and select patients early for a targeted management with modern immunosuppressive drugs [15, 16]. The aim of this retrospective study was to evaluate the frequency of treatment-refractory disease courses among patients with generalized myasthenia gravis according to a strict definition and assess the clinical features of these patients. Methods Patients We retrospectively investigated charts of patients with onset of myasthenia gravis between 2000 and 2016, who were treated at our tertiary neuromuscular center at the Department of Neurology of SB269652 the Medical University of Vienna. We included only patients with sufficient follow-up data of at least 2?years and generalized myasthenia gravis within the first year after onset. Diagnostic criteria for myasthenia gravis consisted of typical myasthenic symptoms in combination with myasthenia gravis-related antibodies, or in seronegative patients either pathological repetitive nerve stimulation with a decrement over 10%, a positive edrophonium chloride test, or documented clinical improvement following pyridostigmine treatment. Disease severity was retrospectively assessed at documented time points using the criteria by the Myasthenia Gravis Foundation of America (MGFA) class [17]. Ethical approval was obtained from the Ethics Committee of the Medical University of Vienna. Outcome measures The primary outcome measure was the occurrence of treatment-refractory MG. We defined treatment-refractory myasthenia gravis at the SB269652 earliest 2?years after diagnosis as soon as the following conditions were met: Persistent moderate to severe myasthenic symptoms (i.e.,??MGFA class III) for the last 12?months test or MannCWhitney test for continuous variables and Chi-squared test for categorical variables. Multivariate logistic regression analyses were used to test for clinical variables associated with the occurrence of treatment-refractory myasthenia gravis. Covariates were selected according to clinical meaningful aspects. The following.