Table 1.

Recommendations for the treatment of anti-MDA5 positive CADM-RPILD^*.

	Set ofRecommendations	RG**
	General management
1	Patients with DM-associated rapidly progressive interstitial lung disease anti-MDA5 (+) should be treated with combination therapy as a first option.	D
	Combination therapy
2	A combination therapy which include glucocorticoids plus a calcineurin inhibitor (cyclosporine A or tacrolimus), or triple therapy adding intravenous cyclophosphamide†ฎ to the previous schedule, are both considered good initial alternatives.	D
2a	Both, cyclosporine A and tacrolimus are considered equally good therapeutic options. The choice of any of them will depend on the safety profile and patients’ characteristics.	√
2b	Monitoring of calcineurin inhibitors blood levels are recommended in order to adjust posology and minimize toxicity.	√
3	When calcineurin inhibitors are not feasible, consider combination therapy with glucocorticoids and other immunosuppressive drugs such as cyclophosphamide†ฎ and/or mycophenolate mofetil☨ or adding rituximab☨ to any one of the previous schedules.	D
3a	The choice of one of these drugs will depend on the individual characteristics of the patient and the clinician experience.	√
	Therapy for the refractory patient
4	In patients with CADM-associated RPILD anti-MDA5 (+) who do not respond to combination therapy with glucocorticoids plus immunosuppressive drugs, clinicians have to take into account the following alternatives:
	- Adding one ofthese immunosuppressive drugs (cyclophosphamide, mycophenolate mofetil, rituximab, basiliximab or tofacitinibʃ) to the current therapy.	D
	- Change one immunosuppressant for another	√
5	In patients who do not respond to combined immunosuppressive drugs, the use of the following alternative rescue therapies, either separate or in a sequential manner, might be considered:
	- Polymyxin B hemoperfusion	D
	- Plasmapheresis	D
	- Intravenous immunoglobulins	√
6	Assistance with ECMO should be considered in patients with life threatening severe and refractory respiratory insufficiency in order to maintain the patient alive while waiting for a clinical response to intensive and combined immunosuppressive treatment or as a bridge to lung transplantation.	√
7	Lung transplantation should be considered as a therapeutic option in patients with refractory RPILD associated to anti- MDA5. Early referral for transplant eligibility assessment is recommended at the time of ILD diagnosis.	√
	Other treatment options
8	Azathioprine, methotrexate and leflunomide are not recommended for the treatment of RPILD associated to anti-MDA5.	√
9	Infliximab is not recommended in anti-MDA-5 associated RPILD treatment	√
10	Although pirfenidone has been added to conventional immunosuppressant treatment in CADM-associated subacute interstitial pneumonia with data of pulmonary fibrosis, the expert panel may not recommend its use in patients with RPILD associated to anti-MDA5.	√

^*Level of evidence was 3 in all the recommendations.

^†ฎAvoid its administration in young female or male who are willing to have offspring.

^☨Avoid its administration in women prone to be pregnant due to the risk of fetal embryopathy.

^ʃThere is not available data on the safety of combined therapy with biologic agents and tofacitinib. Abbreviations: R, Recommendation. RG, Recommendation Grade based on SIGN methodology, see Appendix 1. RPILD, Rapidly Progressive Interstitial Lung Disease. MDA5, Melanoma Differentiation-Associated protein 5. Anti-MDA5, anti-MDA5 antibodies. ECMO, Extracorporeal Membrane Oxygenation.

^**Appendix 1.