Table 3 Recommendations for the treatment of systemic autoimmune myopathies

1. What are the general and educational recommendations for SAM?

The education of individuals with SAM, as well as their families and/or caregivers, is of great importance, since they are looking for environmental adaptations and implementation of rehabilitation programs aiming to maintain/improve the patient’s quality of life. Physical therapy and occupational therapy play a prominent role in the rehabilitation and therapeutic process of patients with SAM (degree of recommendation B)

2. What are some precautions before immunosuppression in patients with SAM?

Immunosuppressive drugs are associated with an increased risk for infections. Therefore, obtaining a thorough medical history with extensive investigation of family history and by directing personnel to obtain information related to the patient’s immunization schedule and infections or other diseases that occur with immunosuppression is of key importance. In general, the risk of these infections is related to the total dose and duration of immunosuppressive drug. The patient’s vaccination status should be evaluated and documented at the first moment after diagnosis of the condition that guides the immunosuppressive drug and the recommended vaccines should be administered as soon as possible. If possible, the delayed vaccine should be given prior to the start of the immunosuppressive drug. Vaccines composed of live attenuated viruses should be administered at least four weeks before the start of the immunosuppressive drug (degree of recommendation B, C, D)

3. What treatment is recommended in the initial phase of SAM?

The administration of GC via oral route is the first-line treatment in cases of SAM (degree of recommendation C). Immunosuppressive drugs with methotrexate, azathioprine and cyclosporine may be associated with a reduction in GC doses (degree of recommendation B)

4. Which drug treatments are recommended for refractory SAM cases?

Evidence suggests that the treatment of refractory cases of SAM with intravenous immunoglobulin, tacrolimus, cyclosporine, cyclophosphamide, azathioprine, methotrexate, abatacept, tocilizumab and rituximab, as monotherapy or in combination, appear to improve muscle strength, CK levels and lung function. However, more controlled studies with greater numbers of patients for evaluation (degree of recommendation B) of efficacy and tolerability are needed. Anti-TNFα agents are not recommended (degree of recommendation C)

5. What initial dose of glucocorticoids should be used and for how long in patients with SAM?

Despite the lack of controlled studies, evidence indicates that first-line treatment should be the administration of GC, starting doses of prednisone or its equivalent potency range from 0.5 to 1.0 mg/kg/day given on a fractional basis, daily or on alternate days. In severe cases, MP pulse therapy should be considered (1 g/day for three consecutive days followed by a regimen with oral GC). Duration and need for association with other immunosuppressive agents are determined by the response of the disease to therapy (degree of recommendation B)

6. How long should SAM patients receive immunosuppressive / immunomodulatory drugs after discontinuation of GC?

There is no established timeframe that determines how long treatment with immunosuppressive/immunomodulatory drugs should be maintained after GC are discontinued. Follow-up evaluations of these individuals should be scheduled according to clinical evolution and changes observed during treatment monitoring (degree of recommendation B)

7. What is the evidence on the benefit of immunosuppressive / immunomodulatory drugs association (association versus exchange) in SAM?

Evidence points to the benefit of the association of immunosuppressive/immunomodulatory drugs in patients with SAM, especially in cases of adverse events with the use of GC in monotherapy, the “sparing” effect of GC, or precautions against the failure to obtain a complete clinical response. Agents such as intravenous immunoglobulin, mycophenolate mofetil, cyclosporine, azathioprine and methotrexate, used alone or in combination appear to contribute to improvement in muscle strength, CK levels and lung function, with no significant difference in efficacy between the treatment schemes (azathioprine with methotrexate, cyclosporine with methotrexate and intramuscular methotrexate with oral methotrexate and azathioprine) (degree of recommendation A)

8. What is the role of rehabilitation, physical exercise and physiotherapy in the treatment of SAM?

The implementation of a physical exercise program (resistance or aerobic physical training or the combination of these two) seems to be safe and beneficial in adult patients with SAM and should be used as a complement to pharmacological treatments in all stages of the disease to maximize muscle performance and aerobic capacity, as well as minimize the risk of side effects caused by GC treatment, for example. Individuals with active disease indication of physical exercises should preferably be instituted as early as possible and be supervised by a physiotherapist in close collaboration with an attending physician to strengthen the muscle groups involved with passive and active exercises (degree of recommendation B)

9. How to monitor disease activity (biomarkers) in patients with SAM?

Evidence has pointed to the possibility of using objective measures, in the form of identification and dosage of molecules that present the potential to discriminate the activity of the disease and predict its damage. (degree of recommendation B)

10 How to define activity versus remission of SAM in clinical practice?

Despite limitations in the study of myopathies, assessment of disease activity or remission is based mainly on clinical presentation and complementary examinations. International groups such as the IMACS have defined instruments that have not yet been fully validated and are largely based on a subjective assessment conducted by both patient and physician on the disease status. It is important to recognize that there is no single gold standard measure to assess disease activity. (degree of recommendation D)