ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1629

Effect of Drug Withdrawal on Interleukin-1 or Interleukin-6 Inhibitor Associated Diffuse Lung Disease

Vivian Saper1, Sampath Prahalad2, Scott Canna3, Rabheh Abdul-Aziz4, Marcela Alvarez5, Catherine Bingham6, Brigitte Bader-Meunier7, Imelda Balboni8, Roberta Berard9, Roxana Bolaria10, Alexis Boneparth11, Alicia Casey12, Elaine Cassidy13, Joyce C. Chang14, Michal Cidon15, Kathleen Collins16, Aileen M. Dickenson17, Graciela Espada5, Martha Fishman12, Elaine Flanagan18, Timothy Hahn19, Ankur K. Jindal20, Ozgur Kasapcopur21, Marisa Klein-Gitelman22, Timothy Klouda12, Mikhail Kostik23, Carol Lake24, Mariana Marques25, Michael Ombrello26, Karen Onel27, Omkar Phadke28, Angelo Ravelli29, Adam Reinhardt30, Amanda D. Robinson31, Kelly Rouster-Stevens32, Nadine Saad27, Grant Schulert33, Susan Shenoi34, Cory Stingl14, Anjali Sura35, Melissa Tesher36, Jessica Tibaldi37, Kathryn Torok38, Cathy Tsin39, Natalia Vasquez-Canizares40, D. Sofia Villacis-Nunez41, Ben Whitehead42, Holly Wobma12, Lawrence Zemel43 and Elizabeth Mellins1, 1Stanford University, Stanford, CA, 2Emory + Children's Pediatric Institute, Atlanta, GA, 3Children's Hospital of Philadelphia, Philadelphia, PA, 4University at Buffalo, Buffalo, NY, 5Hospital de Niños Dr Ricardo Gutierrez, Buenos Aires, Argentina, 6Penn State Children's Hospital, Allentown, PA, 7Pediatric Immuno-hematology, Necker Hospital, APHP, Paris, France, 8Stanford University, Palo Alto, CA, 9London Health Sciences Centre, London, ON, Canada, 10Self, Victoria, BC, Canada, 11Columbia University Medical Center, New York, NY, 12Boston Children's Hospital, Boston, MA, 13University of Pittsburgh Medical Center Medical Education, Pittsburgh, PA, 14Children's Hospital of Phildelphia, Philadelphia, PA, 15Children's Hospital Los Angeles, Los Angeles, CA, 16LeBonheur Children's Hospital, Memphis, TN, 17Children's Hospital of Los Angeles, Los Angeles, CA, 18Emory University and Children's Healthcare of Atlanta, Atlanta, GA, 19Penn State Childrens Hospital, Hershey, PA, 20Postgraduate Institute of Medical Education and Research, Chandigarh, India, 21Istanbul University-Cerrahpasa, Cerrahpasa Medical School, İstanbul, Turkey, 22Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 23Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russia, 24National Institutes of Health, Gaithersburg, MD, 25UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, 26National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, 27Hospital for Special Surgery, New York, NY, 28EMORY, Atlanta, GA, 29Istituto Giannina Gaslini, Genoa, Italy, 30Boys Town National Research Hospital, Omaha, NE, 31UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, 32Emory University/Children's Healthcare of Atlanta, Atlanta, GA, 33Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 34Seattle Children's Hospital, Seattle, WA, 35SUNY Upstate Medical University, Syracuse, NY, 36University of Chicago, Chicago, IL, 37IRCSS Istituto G. Gaslini University of Genoa, Genoa, Italy, 38University of Pittsburgh, Pittsburgh, PA, 39Stanford University, Stanford, 40Children's Hospital at Montefiore, Bronx, NY, 41Children's Healthcare of Atlanta - Emory University, Atlanta, GA, 42Queensland Children's Hospital, Brisbane, Australia, 43CCMC, Hartford, CT

Meeting: ACR Convergence 2021

Keywords: , , , ,

Session Information

Date: Tuesday, November 9, 2021

Title: Pediatric Rheumatology – Clinical Poster III: Miscellaneous Rheumatic Disease (1614–1644)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Severe delayed hypersensitivity reactions (DHR) are under-recognized in inflammatory conditions, particularly drug reaction with eosinophilia and systemic symptoms (DRESS). Previous work has shown this reaction to occur implicating inhibitors of IL-1 and IL-6 during treatment of Stills disease.1 The purpose of the present analysis of newly identified cases is to assess outcomes based on timeliness of recognizing drug reaction and withdrawal of the implicated medications.

Methods: This is a retrospective observational study of subjects with Stills disease who experienced a DRESS reaction implicating one or more of anakinra, canakinumab, tocilizumab or rilonacept. Classification as DHR required scoring as probable or definite using the validated scoring system RegiSCAR for DRESS.2 Cases with and without diffuse parenchymal lung disease during treatment (DLD) were included. Variables included duration of drug exposure, development of diffuse lung disease, lung disease status at data close and death. Lung disease resolution was defined as absence of respiratory symptoms without supplemental oxygen, normal chest CT and resolution or absence of digital clubbing. DLD improvement differed from resolution by allowing improved chest CT or digital clubbing with neither worsening. Comparisons were made using Fishers exact test and odds ratios with 95% confidence intervals. 59 subjects met inclusion criteria for DHR implicating inhibitors of IL-1 and/or IL-6. Class II HLA associations were considered as available.

Results: Median age at Stills onset was 4 years (range 0.5-17.7 years), 69% (41/59) had DLD and 61% (36/59) were female. Fatalities occurred solely in subjects developing DLD (12/41,29%). Median latency from drug initiation to detection of DLD was 1.3 yrs (range 2 weeks-4.3 years). When biopsied, pathology in DLD was pulmonary alveolar proteinosis, as described.1 Three cases resolved lung disease; all 3 had permanently discontinued IL-1 and IL-6 inhibitors within 6 weeks of DLD detection. DHR subjects without DLD who stopped IL-1 or IL-6 inhibitors did not develop DLD, during median follow-up of 1 year after drug stop (range 0.2-6.5 years). Drug withdrawal improved outcomes (table). HLA-DRB1*15 was present in 31/37(84%), strikingly exceeding population frequencies.3

Conclusion: Timely recognition of DRESS reactions and withdrawal of all IL-1 and IL-6 inhibitors improve outcomes in Stills disease, lessens risk of the often fatal drug-associated lung disease and may allow resolution of DLD. Mechanisms underlying cross reactions between these structurally different drugs are not known. Determination of HLA may limit the incidence of DHR.

1. Saper et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. Dec 2019;78(12):1722-1731

2. Kardaun et al. DRESS: an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. Nov 2013;169(5):1071-80.

3. Hollenbach et al. IL-1 and IL-6 inhibitor hypersensitivity link to common HLA-DRB1*15 alleles. https://www.medrxiv.org/content/10.1101/2020.08.10.20172338v3

Disclosures: V. Saper, None; S. Prahalad, Novartis, 1; S. Canna, Simcha Therapeutics, 2, Novartis, 5, AB2Bio, Ltd, 5, IMMvention Therapeutix, 5; R. Abdul-Aziz, None; M. Alvarez, None; C. Bingham, None; B. Bader-Meunier, None; I. Balboni, None; R. Berard, Sandoz, 2, SOBI, 2, Roche, 2; R. Bolaria, None; A. Boneparth, None; A. Casey, None; E. Cassidy, None; J. Chang, None; M. Cidon, None; K. Collins, None; A. Dickenson, None; G. Espada, None; M. Fishman, None; E. Flanagan, None; T. Hahn, None; A. Jindal, None; O. Kasapcopur, Novartis, 6, Pfizer, 6, Roche, 6, Abbvie, 6; M. Klein-Gitelman, None; T. Klouda, None; M. Kostik, None; C. Lake, None; M. Marques, None; M. Ombrello, None; K. Onel, None; O. Phadke, None; A. Ravelli, Abbvie, 2, 6, BMS, 2, 6, Pfizer, 2, 6, Hoffmann-La Roche, 2, 6, Novartis, 2, 6, Centocor, 2, 6, Anjelini Holding, 2, 6, Reckitt Benckiser, 2, 6; A. Reinhardt, None; A. Robinson, None; K. Rouster-Stevens, None; N. Saad, None; G. Schulert, Novartis, 6; S. Shenoi, Pfizer, 2; C. Stingl, None; A. Sura, None; M. Tesher, None; J. Tibaldi, None; K. Torok, None; C. Tsin, None; N. Vasquez-Canizares, None; D. Villacis-Nunez, None; B. Whitehead, None; H. Wobma, Immplacate Inc, 4, 8; L. Zemel, None; E. Mellins, Genentech, 5.

To cite this abstract in AMA style:

Saper V, Prahalad S, Canna S, Abdul-Aziz R, Alvarez M, Bingham C, Bader-Meunier B, Balboni I, Berard R, Bolaria R, Boneparth A, Casey A, Cassidy E, Chang J, Cidon M, Collins K, Dickenson A, Espada G, Fishman M, Flanagan E, Hahn T, Jindal A, Kasapcopur O, Klein-Gitelman M, Klouda T, Kostik M, Lake C, Marques M, Ombrello M, Onel K, Phadke O, Ravelli A, Reinhardt A, Robinson A, Rouster-Stevens K, Saad N, Schulert G, Shenoi S, Stingl C, Sura A, Tesher M, Tibaldi J, Torok K, Tsin C, Vasquez-Canizares N, Villacis-Nunez D, Whitehead B, Wobma H, Zemel L, Mellins E. Effect of Drug Withdrawal on Interleukin-1 or Interleukin-6 Inhibitor Associated Diffuse Lung Disease [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/effect-of-drug-withdrawal-on-interleukin-1-or-interleukin-6-inhibitor-associated-diffuse-lung-disease/. Accessed .

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