Recognizing treatment non-response in anti-MDA5-positive rapidly progressive interstitial lung disease: a trajectory-based framework for parallel escalation

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis complicated by rapidly progressive interstitial lung disease (anti-MDA5-positive RP-ILD) can progress from inflammatory lung injury to refractory respiratory failure within a short and clinically uncertain interval. Existing literature has largely evaluated individual immunomodulatory regimens, prognostic factors or organ-replacement outcomes, but provides limited guidance on when an inadequate early response should be regarded as clinically actionable treatment failure. This gap is important because persistent disease activity may coexist with infection, drug toxicity, pulmonary vascular events, air-leak syndromes and ventilation-related injury, each of which changes the expected benefit and risk of further immunosuppression. In this narrative review, we distinguish treatment non-response, treatment failure and refractory disease as related but non-equivalent concepts. We then organize evidence on treatment exposure, oxygenation and imaging trajectories, inflammatory activity, competing causes of deterioration, respiratory-support requirements and future treatment eligibility into a T0–T6 trajectory-based framework. The framework treats rescue immunomodulation, diagnostic reassessment, critical-care activation and preservation of advanced-support options as parallel decisions rather than consecutive treatment steps. It is intended as a structured communication and research model, not as a validated staging system or prescriptive clinical guideline. Its principal contribution is to define the questions that should be revisited when continued observation may threaten otherwise feasible treatment options.