NextGen 2024: Refractory SJIA & MAS Session Part 6

NextGen 2024: Refractory SJIA & MAS Session Part 6

• 1. Systemic Juvenile Idiopathic Arthritis in China Caifeng Li, MD, PhD Professor of Capital Medical University Chief of Pediatric Rheumatology Department, Beijing Children’s Hospital, National Medical Center for Children Chief of Rheumatology Department, Capital Medical University Executive President of Beijing Children’s Hospital Zhengzhou Hospital

• 2. Treatment of sJIA Treatment of sJIA in Beijing Children's Hospital ◆ sJIA with MAS ◆ sJIA with lung involvement ◆ refractory sJIA Unmet needs and future perspectives Contents

• 3. Commonly used medications for sJIA in China: ◆ Glucocorticoids ◆ NSAIDs ◆ Cyclosporine ◆ Thalidomide ◆ Tocilizumab ◆ JAK inhibitors: Tofacitinib Treatment Plan ◆ general treatment: ● GC+ NSAIDs+ Cyclosporine+ Thalidomide ● GC+ NSAIDs+ Tocilizumab ◆ refractory sJIA treatment: ● GC+ NSAIDs+ Cyclosporine+ Thalidomide+ Tocilizumab/ Tofacitinib ● TNF inhibitors added for patients with chronic arthritis Treatment of sJIA

• 4. Initial treatment data of 546 sJIA cases in BCH ◆ Glucocorticoid: 545 patients (99.8%) initially received, with 501 (91.8%) receiving one dose of MP pulse therapy, 20 received 2 doses MP pulse, 3 received 3 doses MP pulse ◆ Most commonly used DMARDs: CSA (96.3%), MTX (8.4%, primarily for arthritis) ◆ 41 cases (7.5%) used Thalidomide ◆ Biologics and JAK inhibitors: Tocilizumab was the primary choice (16.8%), and 31 cases (5.7%) received Tofacitinib treatment Treatment of sJIA in BCH Initial Treatment Cases Percentage (%) Cyclosporine (CSA) 526 96.3 Ibuprofen 334 61.2 Tocilizumab 92 16.8 Methotrexate (MTX) 46 8.4 Thalidomide 41 7.5 Tofacitinib 31 5.7 TNF-α Inhibitor (TNF-i) 17 3.1

• 5. Follow-up data of 260 sJIA cases in BCH ◆ Treatment plan: Glucocorticoids + NSAIDs + DMARDs + biologics/JAK inhibitors ◆ At 1 month, 74.2% of patients achieved ACRp30 response ◆ At 3 months, 94.2% achieved ACRp30 response ◆ By 24 months ● 100% of patients reached ACRp30 response ● 95.4% achieved ACRp50 response ● 75% reached ACRp70 response Treatment n=260 (%) GC+NSAIDS+DMARDS 186 (71.54) GC+NSAIDS+DMARDS+Tocilizumab 70 (26.92) GC+NSAIDS+DMARDS+Tofacitinib 18 (6.92) GC+NSAIDS+DMARDS+TNF-i 17 (6.53) Treatment of sJIA in BCH

• 6. Clinical data of 141 sJIA-MAS cases in BCH 94 males and 47 females, male-to-female ratio 2:1 Average age of onset: 7.6±3.4 years 16 (11.3%) cases of onset with MAS Clinical Manifestations: the main clinical features included fever (100%), hematologic involvement (95%), and respiratory involvement (90%) ◆ Respiratory involvement: ● pleural effusion: 38 cases (27%) ● acute respiratory distress syndrome: 11 cases (5.7%) sJIA with MAS in BCH Clinical Manifestation Cases (n=141) Percentage (%) Fever 141 100.00% Rash 119 84.40% Arthritis 100 70.09% Hepatomegaly 101 71.63% Splenomegaly 35 24.82% Lymphadenopathy 121 85.11% Nervous System Involvement 19 13.47% Respiratory System Involvement 121 90.78% Cardiovascular system Involvement 110 78.01% Digestive System Involvement 63 44.68% Urinary System Involvement 17 12.05% Hematologic Involvement 134 95.03%

• 7. Treatment data of 70 sJIA-MAS cases in BCH ◆ 70 (100%) received MP pulse therapy ◆ 48 (68.6%) received cyclosporine ◆ The most common treatment plan: ● MP pulse+CSA+ IVIG (38.6%) ● followed by MP pulse + IVIG (28.6%) sJIA with MAS in BCH Treatment Plan Total Cases (%) MP+CSA+IVIG 27 (38.6%) MP+IVIG 20 (28.6%) MP+CSA 12 (17.1%) MP+CSA+IVIG+VP16 4 (5.7%) MP+CSA+IVIG+Biologics 3 (4.3%) MP alone 2 (2.9%) MP+CSA+IVIG+VP16+Biologics 1 (1.4%) MP+CSA+Biologics 1 (1.4%)

• 8. Data of 280 sJIA cases in BCH, including 38 (13.6%) cases with lung involvement male-to-female ratio of 1.5:1, average age of onset: 5.7 ± 3.0 years Among patients with lung involvement, 13 (34.2%) cases had MAS Types of lung involvement: ◆ the main type was interstitial lung disease (92.1%) ◆ pulmonary hemorrhage (10.5%), pulmonary hypertension (5.3%) Clinical Manifestations: fever and respiratory symptoms ◆ mainly cough and chest tightness, 13 (34.2%) required respiratory support sJIA with lung involvement in BCH 35 4 2 1 22 13

• 9. Initial treatment: GC + NSAIDs + DMARDs ◆ 37 (97.4%) used GC, with 73.3% receiving MP pulse therapy ◆ 17 (44.7%) used cyclosporine ◆ 6 (15.8%) added Tocilizumab/JAK inhibitors sJIA with lung involvement in BCH Follow-up: 32 patients for 5-105 months ◆ 26 (81.3%) showed improvement ◆ 22 (68.7%) added tocilizumab ◆ 5 (15.6%) added tofacitinib ◆ 1 patient stopped all medications ◆ 10 cases (31.3%) stopped GC ◆ 3 (9.4%) died due to MAS, pulmonary hemorrhage, respiratory failure, ARDS, and renal failure Medication Initial treatment (%) Follow up (%) Glucocorticoids 97.4 100 High-dose MP Pulse Therapy 73.7 78.1 - 2 cycles 23.7 - 3 cycles 2.6 NSAIDs 57.9 90.5 - Ibuprofen 50 71.8 Cyclosporine 44.7 71.9 Methotrexate 28.9 53.1 Thalidomide 23.7 59.4 Cyclophosphamide 5.3 28.1 Tocilizumab 10.5 68.7 Tofacitinib 2.6 15.6 Ruxolitinib 2.6 Plasma Exchange 10.5 Etoposide (VP16) 2.6

• 10. sJIA with lung involvement in BCH HRCT scans of lungs in some patients during follow-up Before treatment: sJIA-ILD After treatment (58 months) Before treatment: sJIA-ILD After treatment (89 months) Before treatment: sJIA-ILD+MAS After treatment (5 months) Before treatment: sJIA-ILD After treatment (22 months) (Organising pneumonia, OP)

• 11. refractory sJIA in BCH Onset Follow-up Relapse Refractory Reason MAS Treatment Changes Final Follow-up sJIA+MAS 104 months 2 Arthritis 1 GC+NSAIDs+CSA+MTX+Etanercept→Infliximab→Tofacitinib Stop GC, NSAIDs+MTX+Tofacitinib sJIA+MAS+lung 17 months 2 MAS 2 GC+NSAIDs+CSA, give up of treatment sJIA+MAS+lung 66 months 2 MAS 2 GC+CSA+THD+Tocilizumab Stop GC, CSA+MTX+Tocilizumab sJIA 75 months 2 MAS, infection 1 GC+NSAIDs+CSA+Tocilizumab GC+CSA+Tocilizumab sJIA+lung 95 months 7 MAS, infection 2 GC+NSAIDs+CSA+THD+Tocilizumab→Tofacitinib GC+NSAIDs+THD JIA+MAS+lung 54 months 1 MAS 2 GC+NSAIDs+CSA+Tocilizumab Stop GC, NSAIDs+CSA+Tocilizumab sJIA+lung 22 months 2 MAS 1 GC+NSAIDs+CSA+Tocilizumab, give up of treatment sJIA 153 months 4 Arthritis, infection 0 GC+NSAIDs+MTX+THD+Tocilizumab→Tofacitinib Stop GC, NSAIDs+Tofacitinib sJIA 50 months 3 Infection 0 GC+NSAIDs+CSA+THD Currently relapsed, inpatient MP pulse therapy sJIA+MAS 116 months 3 Arthritis, infection 1 GC+NSAIDs+CSA+THD+Tocilizumab→Etanercept→Infliximab →Tofacitinib GC+NSAIDs+THD+Tofacitinib sJIA 25 months 4 MAS, infection 2 GC+NSAIDs+CSA+Tocilizumab→Tofacitinib relapsed again after stopping all medications due to infection GC+CSA+Tocilizumab Data of 11 refractory sJIA cases in BCH: 7 males, 4 females ◆ At onset: average age 3.5 years, 5 onset with MAS, 5 had lung involvement ◆ Reasons for relapse: ● MAS (7, 63.6%), 5 patients experienced 2 times of MAS ● Infection caused disease activity (6, 54.5%) ● Chronic arthritis (2, 18.2%) ◆ Outcomes: 2 give up due to multiple organ failure, 3 achieved disease control with tocilizumab, 5 achieve control with Tofacitinib, and 4 (36.4%) stop GC

• 12. Subsequent Plan - sJIA Database Construction in China ◆ Construct a nationwide multicenter sJIA database ◆ Incorporating 34 tertiary medical institutions ◆ Plan to complete the database construction by December 2024 Unmet needs and future perspectives

• 13. 谢谢各位聆听 THANK YOU！ 13