Experiences with IL-1 Blockade in Systemic Juvenile Idiopathic Arthritis - Data from the German AID-registry

Overview

Journal Pediatr Rheumatol Online J

Publisher Biomed Central

Specialty Pediatrics

Date 2021 Mar 23

PMID 33752669

Citations 5

Authors

Elke Lainka

Melanie Baehr

Bernadette Raszka

Johannes-Peter Haas

Boris Hugle

Nadine Fischer

Dirk Foell

Claas Hinze

Elisabeth Weissbarth-Riedel

Tilmann Kallinich

Gerd Horneff

Daniel Windschall

Eggert Lilienthal

Tim Niehues

Ulrich Neudorf

Rainer Berendes

Rolf-Michael Kuster

Prasad Thomas Oommen

Christoph Rietschel

Thomas Lutz

Frank Weller-Heinemann

Klaus Tenbrock

Georg Leonhard Heubner

Jens Klotsche

Helmut Wittkowski

Affiliations

Soon will be listed here.

Abstract

Background: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with dysregulation of the innate immune system driven by cytokines. A major role is ascribed to interleukin-1β (IL-1β), supporting the autoinflammatory character of the disease and offering an effective blocking mechanism for treatment. Here we present clinical practice data from the German AID-registry for patients treated with IL-1 inhibition (IL-1i).

Methods: In 2009 a clinical and research consortium (AID-Net) was established, including an online AID-registry. Patients with documented sJIA diagnosis were identified. Data for this retrospective IL-1i study were recorded by 17 centers. Response to treatment was evaluated according to Wallace criteria and additionally by an own classifying clinical response system.

Results: In 6 years, 202 patients with confirmed sJIA were recorded in the AID-registry. Out of these, 111 children received therapy with Anakinra (ANA) (n = 84, 39 f) and/or Canakinumab (CANA) (n = 27, 15 f) at a median age of 8.7 y (range 0.6-19.1). During the first 12 months 75/111 (ANA 55, CANA 20) patients were evaluated according to Wallace criteria (achievement of inactive disease 28/55 and 17/20, remission over 6 months under medication 13/55 and 7/20 cases). Over the whole period of time, clinical response was preserved in the majority of patients (ANA 54/80, CANA 20/27). Arthritis mostly persisted in polyarticular (PA) courses. During treatment with IL-1i concomitant medication could be tapered in about 15%. IL-1i was discontinued in 59/111 patients. 45 (15) adverse events (AE)s in ANA (CANA) treated patients (19.7 (26.6) AE/100 ANA (CANA) exposure years, 95%CI: 14.4-26.4 (14.9-43.9)) were reported.

Conclusion: In a large cohort of sJIA patients from Germany, we can confirm an overall favorable clinical response to both available IL-1 blocking agents. IL-1i was well tolerated with acceptable safety and effectiveness in a real-life clinical setting.

Citing Articles

Efficacy and safety of therapies for Still's disease and macrophage activation syndrome (MAS): a systematic review informing the EULAR/PReS guidelines for the management of Still's disease.

Bindoli S, De Matteis A, Mitrovic S, Fautrel B, Carmona L, De Benedetti F Ann Rheum Dis. 2024; 83(12):1731-1747.

PMID: 39317415 PMC: 11671904. DOI: 10.1136/ard-2024-225854.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience.

Qiu L, Ma L, Xie Y, Jin J, Pan Y, Li S Pediatr Rheumatol Online J. 2024; 22(1):38.

PMID: 38504360 PMC: 10949691. DOI: 10.1186/s12969-024-00974-4.

Canakinumab as first-line biological therapy in Still's disease and differences between the systemic and the chronic-articular courses: Real-life experience from the international AIDA registry.

Vitale A, Caggiano V, Maggio M, Lopalco G, Emmi G, Sota J Front Med (Lausanne). 2023; 9:1071732.

PMID: 36619631 PMC: 9813488. DOI: 10.3389/fmed.2022.1071732.

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era.

Ailioaie L, Ailioaie C, Litscher G Int J Mol Sci. 2022; 23(21).

PMID: 36361547 PMC: 9655921. DOI: 10.3390/ijms232112757.

Development and Implementation of the AIDA International Registry for Patients With Still's Disease.

Vitale A, Della Casa F, Lopalco G, Pereira R, Ruscitti P, Giacomelli R Front Med (Lausanne). 2022; 9:878797.

PMID: 35463015 PMC: 9021753. DOI: 10.3389/fmed.2022.878797.

References

Petty R, Southwood T, Manners P, Baum J, Glass D, Goldenberg J . International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004; 31(2):390-2. View

Sota J, Vitale A, Insalaco A, Sfriso P, Lopalco G, Emmi G . Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study. Clin Rheumatol. 2018; 37(8):2233-2240. DOI: 10.1007/s10067-018-4119-x. View

Nigrovic P, Mannion M, Prince F, Zeft A, Rabinovich C, van Rossum M . Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011; 63(2):545-55. DOI: 10.1002/art.30128. View

Gattorno M, Piccini A, Lasiglie D, Tassi S, Brisca G, Carta S . The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008; 58(5):1505-15. DOI: 10.1002/art.23437. View

Wallace C, Ruperto N, Giannini E . Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004; 31(11):2290-4. View

Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C . A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2010; 70(5):747-54. PMC: 3070271. DOI: 10.1136/ard.2010.134254. View

Nigrovic P, Beukelman T, Tomlinson G, Feldman B, Schanberg L, Kimura Y . Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST). Clin Trials. 2018; 15(3):268-277. PMC: 5990441. DOI: 10.1177/1740774518761367. View

Hugle B, Hinze C, Lainka E, Fischer N, Haas J . Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course. Pediatr Rheumatol Online J. 2014; 12:28. PMC: 4127434. DOI: 10.1186/1546-0096-12-28. View

Lainka E, Bielak M, Hilger V, Basu O, Neudorf U, Wittkowski H . Translational research network and patient registry for auto-inflammatory diseases. Rheumatology (Oxford). 2010; 50(1):237-42. DOI: 10.1093/rheumatology/keq270. View

10.

Ruperto N, Brunner H, Quartier P, Constantin T, Wulffraat N, Horneff G . Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012; 367(25):2396-406. DOI: 10.1056/NEJMoa1205099. View

11.

Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H . Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992; 19(3):424-30. View

12.

Martini A, Ravelli A, Avcin T, Beresford M, Burgos-Vargas R, Cuttica R . Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2018; 46(2):190-197. DOI: 10.3899/jrheum.180168. View

13.

Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J . Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005; 201(9):1479-86. PMC: 2213182. DOI: 10.1084/jem.20050473. View

14.

Hinze C, Holzinger D, Lainka E, Haas J, Speth F, Kallinich T . Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany. Pediatr Rheumatol Online J. 2018; 16(1):7. PMC: 5778670. DOI: 10.1186/s12969-018-0224-2. View

15.

Toplak N, Blazina S, Avcin T . The role of IL-1 inhibition in systemic juvenile idiopathic arthritis: current status and future perspectives. Drug Des Devel Ther. 2018; 12:1633-1643. PMC: 5996857. DOI: 10.2147/DDDT.S114532. View

16.

Ter Haar N, van Dijkhuizen E, Swart J, Royen-Kerkhof A, El Idrissi A, Leek A . Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol. 2019; 71(7):1163-1173. PMC: 6617757. DOI: 10.1002/art.40865. View

17.

Ruperto N, Brunner H, Quartier P, Constantin T, Wulffraat N, Horneff G . Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018; 77(12):1710-1719. PMC: 6241618. DOI: 10.1136/annrheumdis-2018-213150. View

18.

Klotsche J, Raab A, Niewerth M, Sengler C, Ganser G, Kallinich T . Outcome and Trends in Treatment of Systemic Juvenile Idiopathic Arthritis in the German National Pediatric Rheumatologic Database, 2000-2013. Arthritis Rheumatol. 2016; 68(12):3023-3034. DOI: 10.1002/art.39796. View

19.

Bruck N, Schnabel A, Hedrich C . Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin Immunol. 2015; 159(1):72-83. DOI: 10.1016/j.clim.2015.04.018. View

20.

Morgan DeWitt E, Kimura Y, Beukelman T, Nigrovic P, Onel K, Prahalad S . Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2012; 64(7):1001-10. PMC: 3368104. DOI: 10.1002/acr.21625. View