Anakinra Drug Retention Rate and Predictive Factors of Long-Term Response in Systemic Juvenile Idiopathic Arthritis and Adult Onset Still Disease

Background and Objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and Methods: This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (p = 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (p = 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p = 0.009), which persisted even after adjustment for pathology (p = 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 [confidence interval (CI) 1.750–5.242], p < 0.0001} and those previously treated with other biologic agents [HR = 1.818 (CI 1.007–3.282), p = 0.047] were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p < 0.0001). Significant corticosteroid-sparing (p = 0.033) and cDMARD-sparing effects (p < 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient’s safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.

[1]  R. Cimaz Systemic-onset juvenile idiopathic arthritis , 2020, Definitions.

[2]  S. Ibrahim,et al.  Racial/Ethnic variations in morbidity and mortality in Adult Onset Still's Disease: An analysis of national dataset. , 2019, Seminars in arthritis and rheumatism.

[3]  G. Cavalli,et al.  Long-Term Retention Rate of Anakinra in Adult Onset Still’s Disease and Predictive Factors for Treatment Response , 2019, Front. Pharmacol..

[4]  K. Lyseng-Williamson Anakinra in Still’s disease: a profile of its use , 2018, Drugs & Therapy Perspectives.

[5]  N. Wulffraat,et al.  Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus , 2018, The Journal of Rheumatology.

[6]  Y. Shoenfeld,et al.  A comprehensive review on adult onset Still's disease. , 2018, Journal of autoimmunity.

[7]  D. Altraide,et al.  Adult onset still's disease: a rare disorder , 2018, International Journal of Research in Medical Sciences.

[8]  S. Özen,et al.  Anakinra treatment in macrophage activation syndrome: a single center experience and systemic review of literature , 2018, Clinical Rheumatology.

[9]  K. Lyseng-Williamson Methylphenidate extended-release orally disintegrating tablets (Cotempla XR-ODT™) in attention-deficit hyperactivity disorder in children aged 6–17 years: a profile of their use , 2018 .

[10]  D. Rigante A developing portrait of hereditary periodic fevers in childhood , 2018 .

[11]  E. Feist,et al.  Adult onset Still's disease-The evidence that anti-interleukin-1 treatment is effective and well-tolerated (a comprehensive literature review). , 2017, Seminars in arthritis and rheumatism.

[12]  G. De Sarro,et al.  Biologic drugs in adult onset Still’s disease: a systematic review and meta-analysis of observational studies , 2017, Expert review of clinical immunology.

[13]  L. Punzi,et al.  Response to Interleukin-1 Inhibitors in 140 Italian Patients with Adult-Onset Still’s Disease: A Multicentre Retrospective Observational Study , 2017, Front. Pharmacol..

[14]  S. Savic,et al.  Interleukin-1 Blockade: An Update on Emerging Indications , 2017, BioDrugs.

[15]  R. Cimaz,et al.  Investigational drugs for treatment of juvenile idiopathic arthritis , 2017, Expert opinion on investigational drugs.

[16]  D. Rigante A systematic approach to autoinflammatory syndromes: a spelling booklet for the beginner , 2017, Expert review of clinical immunology.

[17]  A. Ravelli,et al.  IL-1 Inhibition in Systemic Juvenile Idiopathic Arthritis , 2016, Front. Pharmacol..

[18]  M. Valenti,et al.  Adult-onset Still’s disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers , 2016, BMC Medicine.

[19]  K. Fushimi,et al.  Epidemiological study of adult-onset Still’s disease using a Japanese administrative database , 2016, Rheumatology International.

[20]  S. Huffel,et al.  Bath Ankylosing Spondylitis Functional Index Shows Promising Reliability and Validity in the Assessment of Activity Limitations in Axial Spondyloarthritis , 2016, The Journal of Rheumatology.

[21]  S. Bombardieri,et al.  Adult-onset Still’s disease: an Italian multicentre retrospective observational study of manifestations and treatments in 245 patients , 2016, Clinical Rheumatology.

[22]  Sathish Kumar Systemic Juvenile Idiopathic Arthritis: Diagnosis and Management , 2016, The Indian Journal of Pediatrics.

[23]  V. Pascual,et al.  Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab , 2016, Arthritis & rheumatology.

[24]  A. Brachat,et al.  Gene-expression analysis of adult-onset Still’s disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity , 2015, Pediatric Rheumatology.

[25]  M. González-Gay,et al.  Efficacy of Anakinra in Refractory Adult-Onset Still's Disease , 2015, Medicine.

[26]  F. De Benedetti,et al.  Anakinra in Systemic Juvenile Idiopathic Arthritis: A Single-center Experience , 2015, The Journal of Rheumatology.

[27]  M. Galeazzi,et al.  Interleukin-1 as a Common Denominator from Autoinflammatory to Autoimmune Disorders: Premises, Perils, and Perspectives , 2015, Mediators of inflammation.

[28]  C. Wouters,et al.  Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients , 2014, Arthritis & rheumatology.

[29]  C. Sandborg,et al.  Randomized, Double‐Blind, Placebo‐Controlled Trial of the Efficacy and Safety of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis , 2014, Arthritis & rheumatology.

[30]  P. Sève,et al.  Adult-onset Still's disease. , 2014, Autoimmunity reviews.

[31]  P. Nigrovic Review: Is There a Window of Opportunity for Treatment of Systemic Juvenile Idiopathic Arthritis? , 2014, Arthritis & rheumatology.

[32]  L. Punzi,et al.  Working the endless puzzle of hereditary autoinflammatory disorders , 2014, Modern rheumatology.

[33]  N. Wulffraat,et al.  Effectiveness of First‐Line Treatment With Recombinant Interleukin‐1 Receptor Antagonist in Steroid‐Naive Patients With New‐Onset Systemic Juvenile Idiopathic Arthritis: Results of a Prospective Cohort Study , 2014, Arthritis & rheumatology.

[34]  Z. Amoura,et al.  Anakinra in Adult‐Onset Still's Disease: Long‐Term Treatment in Patients Resistant to Conventional Therapy , 2013, Arthritis care & research.

[35]  P. Woo,et al.  Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis , 2013, Arthritis care & research.

[36]  M. Gahr,et al.  Anakinra: A safe and effective first-line treatment in systemic onset juvenile idiopathic arthritis (SoJIA) , 2012, Rheumatology International.

[37]  H. Kautiainen,et al.  Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-onset Still’s Disease. An Open, Randomized, Multicenter Study , 2012, The Journal of Rheumatology.

[38]  C. Suh,et al.  Therapeutic responses and prognosis in adult-onset Still’s disease , 2012, Rheumatology International.

[39]  I. Koné-Paut,et al.  Is Still's Disease an Autoinflammatory Syndrome? , 2012, International journal of inflammation.

[40]  R. Cimaz,et al.  Bridging the Gap between the Clinician and the Patient with Cryopyrin-Associated Periodic Syndromes , 2011, International journal of immunopathology and pharmacology.

[41]  C. Macaubas,et al.  Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions , 2011, Nature Reviews Rheumatology.

[42]  A. Tzioufas,et al.  Efficacy and long-term follow-up of IL-1R inhibitor anakinra in adults with Still's disease: a case-series study , 2011, Arthritis research & therapy.

[43]  Andrew I. Shulman,et al.  Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. , 2011, Arthritis and rheumatism.

[44]  R. Priori,et al.  Adult-onset Still disease: a rare disorder with a potentially fatal outcome , 2010, Autoimmunity Highlights.

[45]  L. Astudillo,et al.  May anakinra be used earlier in adult onset Still disease? , 2010, Clinical Rheumatology.

[46]  J. Sibilia,et al.  Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France , 2007, Annals of the rheumatic diseases.

[47]  V. Pascual,et al.  Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade , 2005, The Journal of experimental medicine.

[48]  J. Verbsky,et al.  Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. , 2004, The Journal of rheumatology.

[49]  M. Suarez‐Almazor,et al.  International League of Associations for Rheumatology: International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001 , 2004 .

[50]  D. Trock,et al.  Successful treatment of a patient with refractory adult-onset still disease with anakinra. , 2003, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[51]  J. Dequeker,et al.  Globalization of rheumatology: activities of ILAR. Think global--act local. International League of Associations for Rheumatology. , 2001, The Journal of rheumatology.

[52]  Tony Travers,et al.  A Comprehensive Review , 1998 .

[53]  M. Akizuki,et al.  Preliminary criteria for classification of adult Still's disease. , 1992, The Journal of rheumatology.

[54]  M. Govoni,et al.  Adult-onset Still’s disease , 2009, Rheumatology International.

[55]  F. Hayem Is Still's disease an autoinflammatory syndrome? , 2009, Joint, bone, spine : revue du rhumatisme.

[56]  G. Cook,et al.  Primer: inflammasomes and interleukin 1β in inflammatory disorders , 2008, Nature Clinical Practice Rheumatology.

[57]  C. Werning [Rheumatoid arthritis]. , 1983, Medizinische Monatsschrift fur Pharmazeuten.

[58]  Extended Report , 2022 .