Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Rare Pulmonary Diseases in Systemic JIA

1,731 views

Published on

Rare Pulmonary Diseases in Systemic JIA. This presentation tracks the increased use of biologics to treat SJIA and observes the trends in rare pulmonary diseases.

Published in: Healthcare
  • I have recently read your book and must congratulate you on the most informative and revolutionary contents. Your book has drastically changed my life and the way I view health. I am so grateful for your discovery of this information and for sharing it with the world. ■■■ http://t.cn/A6vI6BAP
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

Rare Pulmonary Diseases in Systemic JIA

  1. 1. Rare Pulmonary Diseases in Systemic JIA Yukiko Kimura, MD Professor of Pediatrics Joseph M Sanzari Children’s Hospital Hackensack University Medical Center Chair Elect Childhood Arthritis & Rheumatology Research Alliance
  2. 2. sJIA Treatment Overview: Pre-Biologics • NSAIDs and aspirin • Glucocorticoids • Methotrexate • Cyclosporine • Thalidomide • Cyclophosphamide • Hematopoietic stem cell transplantation
  3. 3. Treatment of sJIA with Biologics: TNF inhibitors • Etanercept – First available biologic – Disappointing response • Quartier P et al (Arthritis Rheum 2003) • Kimura Y et al (J Rheum 2005) • Infliximab – Limited success – Higher doses able to be given (20mg/kg every 2-4 weeks) • Anti-TNF used for mostly arthritis vs systemic disease • Ringold S et al (Arthritis Care Res 2013): JIA treatment guidelines update
  4. 4. IL-1 inhibition in sJIA Pascual V et al JEM 201; 2005 Nigrovic P et al. Arthritis Rheum 63; 2011
  5. 5. Other IL1 inhibitors: Canakinumab (IL1 beta mAb) Ruperto N, et al. NEJM 367;25, 2012
  6. 6. IL6 inhibition in sJIA Tocilizumab (IL6r mAb) DeBenedetti F, et al. NEJM 367:25, 2012
  7. 7. The CARRA Registry of Pediatric Rheumatic Diseases 70% 10% 7% 4% 2% 2% 2% 1%1% 1% 0% 0% N = 8533 JIA (5965) SLE (876) JDM(568) L Scl (324) Vasculitis(176) MCTD(147) JPFS (164) Uveitis(77) Autoinflammatory(58) SS (52)
  8. 8. Current vs Ever Used Medications in sJIA CARRA Registry Patients 0 20 40 60 80 100 Current Use Ever Used N=418
  9. 9. Current medication usage patterns CARRA Registry sJIA Patients
  10. 10. BACKGROUND Pulmonary Disease in SJIA • Isolated case reports of pulmonary disease in sJIA and Adult Onset Still’s Disease – Pulmonary Hypertension (PH) – Interstitial Lung Disease (ILD) – Alveolar Proteinosis (AP) – Lipoid Pneumonia (LP) • Increased spontaneous reporting of cases through pediatric rheumatology listserv since 2008 • Concern regarding potential recent triggers including exposure to biologic agents • Study aims: – Identify sJIA patients who developed rare pulmonary diseases – Assess medication exposures and disease characteristics – Compare patients and medications to CARRA Registry sJIA patients
  11. 11. METHODS • Retrospective review of pulmonary disease cases in sJIA solicited through a pediatric rheumatology listserv • Questionnaire – Demographic features – Systemic JIA disease features – Pulmonary disease features – Medication exposures – Outcomes • Comparisons made to baseline data obtained of sJIA patients in the CARRA Registry
  12. 12. Patient Cohorts • Study cohort (n=25) – PH: 16 (64%) – ILD: 7 (28%) – AP: 3 (12%) – LP: 2 (8%) – 6 combination • PAH and ILD (3) • PAH and LP (1) • PAH and AP (1) • ILD and LP (1) • CARRA Registry cohort (n=389) – Systemic JIA patients enrolled as of 4/30/12
  13. 13. Demographic Features Study Cohort N=25 CARRA Registry N=389 P value sJIA diagnosis age (yrs) 7.4 + 6 (1-17) 5.8 + 4 (0.2-16) NS Race/Ethnicity NS Caucasian 17 (68) 302 (78) Black 7 (28) 45 (12) Asian 1 (4) 20 (5) Other 0 (0) 20 (5) Hispanic 5 (20) 50 (13) Country of residence US (19), Brazil (2), Italy (1), Spain (1), UK (1), Netherlands (1) US (all) Disease duration (mos) 51.6 + 29 (8-173) 62 + 51 (0.6-220) 0.012 Female 19 (76%) 213 (55%) 0.04
  14. 14. sJIA Disease Features Feature Study Cohort CARRA Registry P value Arthritis 25 (100%) 378 (100%) NS Fever 25 (100%) 353 (93%) NS Rash 34 (92%) 326 (87%) NS Hepato/splenomegaly 20 (80%) 102 (31%) <0.001 Lymphadenopathy 19 (76%) 147 (46%) <0.001 Serositis 14 (56%) Unknown MAS 20 (80%) Unknown
  15. 15. Pulmonary Disease Features • Pulmonary symptoms – Dyspnea on exertion: 18 (72%) – Shortness of breath: 16 (64%) – Cough: 11 (44%) – Clubbing: 10 (40%) – Chest pain: 5 (20%) • Pulmonary disease duration at last follow up – Median: 30 (IQR 19-58) months • Months between symptoms to diagnosis – Median: 1 (0-5) months – One patient diagnosed at autopsy
  16. 16. Systemic Disease Features at Pulmonary Disease Onset • 23 (92%) had concomitant systemic features – Fever (15) – Splenomegaly (12) – Serositis (11) – Hepatomegaly (11) – Rash (7) – Lymphadenopathy (6) • 16 (64%) had Macrophage Activation Syndrome – 15 (60%) fulfilled Ravelli criteria (J Pediatr 146(5) 2005) – 5 had positive tissue confirmation – 1 had hemophagocytosis in multiple organs at autopsy
  17. 17. Concurrent Meds at Pulmonary Diagnosis* Medication Number (%) Mean exposure (mos) Glucocorticoids 24 (96) 47 + 48 (3-161) Methotrexate 13 (52) 33 + 38 (1-126) Cyclosporine 7 (28) 6 + 7 (1-22) Any biologic 17 (68) IL1 inhibitor (any) 12 (48) 15 + 15 (3-47) Anakinra 10 (40) 17 + 16 (3-47) Canakinumab 1 (4) 6 Rilonacept 1 (4) 6 TNF inhibitor (any) 3 (12) 17 + 13 (2-26) Adalimumab 2 (8) 13 + 15 (2-23) Etanercept 1 (4) 26 Tocilizumab 2 (8) 6 + 7 (1-11) Etoposide, thalidomide, gold 1 each (4) *or d/c’d within a month prior to diagnosis
  18. 18. Exposure to Non-biologics: Cohort vs Registry Medication (ever used) Study cohort CARRA Registry P value Prednisone 25 (100%) 336 (86%) NS IV steroid pulses 23 (92%) 122 (31%) <0.001 Methotrexate 22 (88%) 232 (78%) NS Cyclosporine 18 (72%) 45 (12%) <0.001 Cyclophosphamide 5 (20%) 7 (2%) 0.001 Etoposide 6 (24%) Not reported Thalidomide 4 (16%) Not reported Tacrolimus 2 (8%) 8 (2%) NS Mycophenolate 3 (12%) 12 (3%) NS Gold 1 Not reported Penicillamine 1 Not reported
  19. 19. Exposure to Biologics: Cohort vs Registry Medication (ever used) Study cohort CARRA Registry P value IL1 Inhibitor (any) 20 (80%) 168 (43%) <0.001 Anakinra 20 (80%) 156 (40%) <0.001 Canakinumab 3 (12%) 7 (2%) <0.001 Rilonacept 4 (16%) 27 (7%) 0.018 Tocilizumab 5 (20%) 29 (8%) 0.044 IVIG 7 (28%) 24 (6%) 0.001 TNF inhibitor (any) 15 (60%) 174 (45%) NS Rituximab 0 2 (1%) NS
  20. 20. Year of Onset of Systemic JIA & Pulmonary Disease Study Cohort N=25 CARRA Registry N=89 P value Decade of sJIA disease onset 0.0068 1980’s 1 (4%) 0 1990’s 5 (20%) 35 (9%) 2000 and later 19 (76%) 335 (87%) Pulmonary disease onset Prior to 2000 1 (4%) NA 2000-2004 4 (16%) NA 2005 and after 20 (80%) NA
  21. 21. Mortality • 17 of 25 patients (68%) died as of June 2012 – Mean time to death (from pulmonary disease onset) • 10 + 13 (0-44) months – Diagnoses: • PH (11), AP (4), ILD (3) • PH+ILD, PAH+AP, AP+ILD (1 of each) • 8 surviving patients as of June 2012 – Mean survival: 56.2 ± 35.3 (range 16-106) months – Diagnoses • PH (5), AP (2), ILD (4) • PH+ILD (2), PAH+AP (1) • As of Feb 2015: – 6 alive – 2 died (1 after MUD BMT): 1 PH, 1 PH+ILD
  22. 22. Treatments given after pulmonary disease • Cyclophosphamide – 4 of 5 patients used post pulmonary disease – 2 of 4 patients alive • Etoposide – 5 of 6 patients post pulmonary disease – 2 of 5 patients alive • Cyclosporine – 15 of 18 patients post pulmonary disease – 5 of 15 patients alive • Combination – Etoposide+Cyclosporine: 4 (1 alive) – Cyclophosphamide+Cyclosporine: 4 (2 alive)
  23. 23. Other treatments • Incompletely reported with mixed results • Immunosuppressive meds – Anakinra, pulse IV and oral steroids, mycophenolate, tacrolimus, thalidomide • Lung disease specific treatments – Bosentan, nitric oxide, sildenafil, albuterol, whole lung lavage
  24. 24. CONCLUSIONS • PH, ILD, LP and AP are potentially fatal, under- recognized complications of systemic JIA • Associated with severe uncontrolled systemic disease, including MAS • Most known cases reported after 2000 • Increased exposure to biologic medications (especially IL1 inhibitors)
  25. 25. Thanks – Jennifer Weiss – Kathryn Haroldson – Tzielan Lee – Marilynn Punaro – Sheila Oliveira – Egla Rabinovich – Meredith Riebschleger – Jordi Anton – Peter Blier – Valeria Gerloni – Melissa Hazen – Elizabeth Kessler – Karen Onel – Murray Passo – Robert Rennebohm – Carol Wallace – Patricia Woo – Nico Wulffraat
  26. 26. Acknowledgments CARRA Registry Investigators  L Abramson  T Beukelman  J Birmingham  S Bowyer  E Chalom  F Dedeoglu  P Ferguson  D Goldsmith  B Gottlieb  T Graham  R Hollister  A Huttenlocher  N Ilowite  L Imundo  S Prahalad  A Quintero  S Ringold  D Rothman  N Ruth  C Sandborg  K Schikler  D Sherry  N Singer  S Spalding  R Syed  K Torok  R Vehe  E von Scheven  A White  A Yalcinadg  L Zemel  C Inman  R Jerath  L Jung  P Kahn  D Kingsbury  M Klein-Gitelman  T Lehman  C Lindsley  D McCurdy  N Moorthy  B Myones  A Lasky  J Lopez-Benitez  J Olson  K O’Neil  K Nanda  K Peterson

×