Latest Advances in Connective Tissue Disorders
Simon Bowman, PhD, FRCP, Vijay Rao, MRCP
Ther Adv Musculoskel Dis. 2013;5(4):234-249.
Polymyositis and dermatomyositis (DM) are the two major forms of idiopathic inflammatory myopathies (IIMs) [Miller, 2012]. Inclusion body myositis (IBM) is a third important subgroup of IIM. IBM is associated histologically with fewer inflammatory changes and with the presence of basophilic granular inclusions, rimmed vacuoles and eosinophilic cytoplasmic inclusions. Involvement of the long flexors of the hands and a particularly high risk of falls might suggest IBM. DM has also been linked to malignancy, particularly in older patients [Callen, 1994].
Corticosteroids are the usual first-line therapy, for example, prednisolone 1 mg/kg/day initially at least for 4–12 weeks and then tapered after a month by 10–20% of the daily dose monthly to the lowest possible maintenance dose. There are small, randomized trials of conventional disease-modifying antirheumatic drugs, such as methotrexate, azathioprine, ciclosporin, tacrolimus, cyclophosphamide or mycophenolate [Gordon et al. 2012; Aggarwal and Oddis, 2012] (http://www.controlled-trials.com/ISRCTN40085050), demonstrating only modest effects. IBM is less likely to respond and in a patient who is not responding to immunosuppressant therapy the diagnosis of IBM should be carefully considered, if need be with a second muscle biopsy. Motor neurone disease is another differential to consider.
In patients resistant to corticosteroids, IVIG has been identified as a promising second-line therapy [Wang et al. 2012]. Dastmalchi and colleagues reported on a 14-week open-label trial with infliximab in 13 refractory patients showing no benefits but more adverse events [Dastmalchi et al. 2008]. In addition, some biological therapies, particularly rituximab, may have a role, although larger studies are needed [Dalakas, 2010]. The Rituximab in Myositis (RIM) study presented in ACR 2011 failed to meet the primary and secondary end points but a large number of patients met the International Myositis Assessment and Clinical Studies Group (IMACS) definition of improvement.
Myositis is associated with long-term disability in 80% of patients and has a standardized mortality ratio three times higher than the general population [Marie, 2012]. Screening early and often for ILD in particular with lung function tests and HRCT is advisable.
One of the challenges with rare diseases is the difficulty of validating assessment tools that can be used to assess improvement in clinical trials. International collaborations such as IMACS and the Paediatric Rheumatology International Trials Organisation have been working to develop individual measures and have also proposed preliminary definitions of improvement [Rider et al. 2011; Miller, 2012].
In the absence of major therapeutic advances the key recent development in myositis has been the use of novel autoantibodies to classify patients and as potential prognostic indicators (Table 1).