NextGen 2024: Monitoring &Treating Lung Disease in SJIA Session Part 1

NextGen 2024: Monitoring &Treating Lung Disease in SJIA Session Part 1

• 1. Monitoring & Treating Lung Disease in Still’s Disease Claudia Bracaglia Division of Rheumatology Ospedale Pediatrico Bambino Gesù Roma - Italy claudia.bracaglia@opbg.net

• 2. 61 SD-LD patients from 21 Ped Rheum Centres European Registry on SD associated LD Clinical characteristics N = 61 Ethnicity - White-Caucasian - Black 59 2 Female 38 (62%) Age at SD onset 7.2 yrs Age at LD onset 9.9 yrs Trisomy 21 3 (5%) SD course - chronic persistent - polycyclic - monocyclic 54% 43% 3% Arthritis at SD onset 74% Active SD at LD diagnosis 79% History of MAS - SD onset - LD diagnosis - >1 episode of MAS 85% 44% 59% 71% Lung features N = 61 LD features: - ILD - PAP - PAH 82% 10% 6% Clinical manifestation - acute digital clubbing - cough - dyspnoea - hypoxia - pulmonary hypertension 46% 47% 36% 34% 18% Chest CT - Septal thickening - Peri-bronchovascolar thickening - Ground glass opacities 98% 82% 55% 58% Bronchoalveolar lavage 43% Lung biopsy - Alveolar proteinosis - Endogenous lipoid pneumonia - Vasculitis - Fibrosis 25% 26% 20% 6% 6% IL-18 levels (pg/ml) 22/61 Media (range) -SD onset -LD diagnosis -Last follow-up visit 12/61 17/61 18/61 121451 (1447- 515100) 138947 (8416 – 515100) 26426 (1292 - 151930) Eosinophils (cell/mmc) 55/61 >1.000 cell/mmc - SD onset - LD diagnosis - Last follow-up visit 46/61 53/61 52/61 9 (19%) 14 (26%) 9 (17%) HLA-DRB1 29/61 48% - HLA-DRB1*15 - HLA-DRB1*11 22/29 12/29 76% 41%

• 3. 61 SJIA-LD patients from 21 Ped Rheum Centres European Registry on sJIA associated LD Patients who did not receive IL-1/IL-6 inhibitors before LD diagnosis N = 12 ILD 12/12 Active MAS at LD diagnosis 6/12 ICU 6/12 Died 2/12 Treatment N = 61 IL-1/IL-6 inhibitors before LD diagnosis - Anakinra - Canakinumab - Tocilizumab 49/61 (80%) 67% 57% 57% Drug adverse reaction to a cytokine inhibitor - Tocilizumab - Anakinra - Anakinra and Tocilizumab 27/61 (44%) 17/27 10/27 2/27 Treatment after LD diagnosis N = 61 (%) Glucocorticoids (GCs) 54 (88%) Cyclosporine-A 27 (44%) MMF 10 (16%) Methotrexate 13 (21%) Anakinra 32 (52%) Canakinumab 29 (47%) Tocilizumab 19 (31%) Baricitinib 10 (16%) Tofa/Ruxo 3 (5%)/2 (3%) Emapalumab 7 (11%) Etoposide 3 (5%) Sirolimus 1 (2%) MAS825 4 (6%) IVIG 16 (26%) HSCT 7 (11%) Outcome N = 61 (%) SD in CID at last follow-up 35 (57%) LD course • Improved • Stable • Worsened 23 (38%) 23 (38%) 14 (22%) LD complication • Hypoxia • Oxygen supplementation • Pulmonary hypertension 21 (34%) 12 (57%) 8 (38%) 8 (38%) ICU admission 29 (47%) Death 11 (18%)

• 4. SD associated LD Bambino Gesù experience SJIA-LD (n=6) Female 3 (50%) Aget at SD onset (range) 4.5 years (4 mo – 13.4 yrs) Age at LD onset (range) 5.3 years (2 yrs – 15 yrs) Trisomy 21 0 MAS - Recurrent episodes 5 (83%) 4 (66%) Hypereosinophilia (EoS>1000 mmc at least in two occasions) 3 (50%) IL-18 pg/ml 307588 (74564 – 515100) HLA-DRB1*15 5 (83%) HLA-DRB1* 11 5 (83%)

• 5. SD associated LD Bambino Gesù experience SJIA-LD (n=6) Exposure to IL-1/IL-6 inhibitors before LD diagnosis - Anakinra - Anakinra and Canakinumab - Anakinra and Tocilizumab 5 (83%) 3 1 1 Drug reaction - Tocilizumab - Anakinra 4 (66%) 3* 1 No exposure to IL-1/IL-6 inhibitors before LD diagnosis 1 (16%) *The reaction occurred after the first and the third administration of TCZ in 1 pt. LD developed before the drug reaction in 2 pts.

• 6. SD associated LD Bambino Gesù experience Treatment after LD diagnosis SJIA-LD (n=6) - IV GC - Anakinra - Canakinumab - Tocilizumab - Cyclosporine - MMF - Sirolimus - Ruxolitinib - Emapalumab - MAS825 6 4 5 3 5* 3** 1 1 2 4 *2 pts were already on cyclosporine before LD diagnosis **3 pts switched from cyclosporine to MMF after LD diagnosis

• 7. SD associated LD Bambino Gesù experience Treatment after LD diagnosis SJIA-LD (n=6) - IV GC - Anakinra - Canakinumab - Tocilizumab - Cyclosporine - MMF - Sirolimus - Ruxolitinib - Emapalumab - MAS825 6 4 5 3 5* 3** 1 1 2 4 Outcome - 1 pt improved with IL-1i and MMF - 2 pts improved with MAS825 - 1 pt stable with emapalumab - 1 pt worsened despite MAS825 and she now on emapalumab - 1 pt developed LD on sirolimus - No pt developed LD complication - No pt died *2 pts were already on cyclosporine before LD diagnosis **3 pts switched from cyclosporine to MMF after LD diagnosis