Patients with severe, rapidly progressive diffuse interstitial lung disease (RP ILD) with anti-MDA5 have an appalling prognosis and the lack of effective medical treatment leads to lung transplantation being proposed as salvage treatment. Currently, transplant-free survival at 90 days (D90) is approximately 25%, dropping to less to 10% among those requiring mechanical ventilation. Peripheral lymphopenia and elevated anti-MDA5 antibody levels are associated with greater disease severity, highlighting the involvement of mature T and B lymphocytes in disease pathogenesis.

Teclistamab, a bispecific antibody targeting the B-cell maturation antigen (BCMA) on plasma cells and engaging T cells - approved for the treatment of refractory multiple myeloma - has recently shown rapid and promising effects in patients with autoimmune conditions, including one MDA5-positive patient, while maintaining a favourable safety profile. We hypothesize that this bispecific antibody could represent a promising and safe therapeutic option for patients with severe MDA5-associated RP-ILD.

Inclusion Criteria:

• Patient ≥ 18 years old
• MDA5 antibody positivity
• ILD confirmed by chest HRCT
• Within less than 3 months after disease onset
• Refractory after more than 7 days to high dose steroids and two immunosuppressants drugs as first-line treatment.
• Confirmation of refractoriness by the national emergency multidisciplinary discussion (MDD),
• Worsening of respiratory symptoms with respiratory distress defined by increase in oxygen supply to reach SpO2>95% or requirement of mechanical ventilation
• Written informed consent obtained from the patient or the trusted support person designated in advance by the patient
• Patients covered by the French social security system
• Effective contraception for woman of childbearing age during treatment and for five months after the last dose of teclistamab.
• Effective contraception for men, having a partner of childbearing age, during treatment and for three months after the last dose of teclistamab.

Exclusion Criteria:

• Patient with known hypersensitivity to teclistamab, substance active or excipients, including sodium or polysorbate
• Patient or the trusted person designed by the patient not able to give their consent
• Known diagnosis of a serious comorbidity: active cancer, malignant blood disease, ongoing infection, stroke or seizure within 6 months
• Patient who received a live vaccine within 4 weeks prior to study inclusion.
• Patient under judicial protection, deprivation of liberty
• Patient participating in another clinical trial with an investigational medicinal product
• Pregnant or breastfeeding woman
• Patient on AME (state medical aid)