interleukin 1 inhibition with anakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety

Background: Anakinra is the first interleukin-1 inhibitor to be used in clinical practice, and recent evidence showed that interleukin-1 plays a pivotal role in the pathogenesis of adult-onset Still disease (AoSD). However, data concerning efficacy with anakinra use in different clinical trials has not been evaluated, and the overall remission of AoSD with anakinra treatment has not been well defined. Methods: We conducted a search on Embase, PubMed, and the Cochrane Library for relevant trials. Statistical analyses were conducted to calculate the overall remission rates, odds ratios (OR), and 95% confidence intervals (CI), by using either random effects or fixed effect models according to the heterogeneity. Results: Of the 273 articles that were identified, 265 were excluded. Eight studies were eligible for inclusion. The overall remission rate and complete remission rate of anakinra in AoSD patients were 81.66% (95% CI: 69.51%–89.69%) and 66.75% (95% CI: 59.94%–75.3%), respectively. Compared with the controls, the use of anakinra was associated with a significant remission in AoSD, with an OR of 0.16 (95% CI: 0.06–0.44, P = 0.0005). There were also significant reductions of the dosage of corticosteroid (mean difference = 21.19) (95% CI: 13.2–29.18, P  0.0001) from anakinra onset to the latest follow up time. Clinical and laboratory parameters were all improved, and anakinra was well tolerated in patients with AoSD. No evidence of publication bias was observed. Conclusion: Our study has shown that anakinra is effective in remitting the manifestations of AoSD, with reduction of the dose of corticosteroid in patients with AoSD. Further, anakinra therapy was not associated with increased risk of adverse events, and it was well tolerated in patients with AoSD. Further research is still recommended to investigate these Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic

[1]  D. Maucort-Boulch,et al.  Adult-Onset Still Disease , 2014, Medicine.

[2]  J. Jun,et al.  Interleukin-18 as an efficient marker for remission and follow-up in patients with inactive adult-onset Still’s disease , 2014, Scandinavian journal of rheumatology.

[3]  R. Fontana,et al.  Meta‐analysis: the impact of oral anti‐viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B , 2013, Alimentary pharmacology & therapeutics.

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

[5]  C. Gogos,et al.  Granulomas Formation in Lymph Nodes, Liver and Spleen in Adult-Onset Still’s Disease: A Case Report , 2013, Journal of clinical medicine research.

[6]  C. Gogos,et al.  Suppurative necrotizing granulomatous lymphadenitis in adult-onset Still’s disease: a case report , 2012, Journal of Medical Case Reports.

[7]  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.

[8]  S. Das,et al.  An Unusual Presentation of Adult Onset Still's Disease. , 2012, The Medical journal of Malaysia.

[9]  J. Zhong,et al.  Adult-onset Still’s disease: how to make a diagnosis in an atypical case , 2012, Rheumatology International.

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

[11]  B. Fautrel,et al.  Anti-Interleukin-1 Agents in Adult Onset Still's Disease , 2012, International journal of inflammation.

[12]  R. Fontana,et al.  Meta‐analysis: oral anti‐viral agents in adults with decompensated hepatitis B virus cirrhosis , 2012, Alimentary pharmacology & therapeutics.

[13]  Z. Varga,et al.  Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a patient with adult Still's disease during treatment with interleukin 1 receptor antagonist anakinra: a case report , 2011, Journal of Medical Case Reports.

[14]  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.

[15]  J. Sibilia,et al.  Tocilizumab in refractory adult Still's disease , 2011, Arthritis care & research.

[16]  G. Schett,et al.  Successful treatment of adult-onset Still's disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade , 2010, Annals of the rheumatic diseases.

[17]  Fengchun Zhang,et al.  Clinical features and prognosis in adult-onset still's disease: a study of 104 cases , 2010, Clinical Rheumatology.

[18]  M. Ffrench,et al.  Reactive Hemophagocytic Syndrome in Adult-Onset Still Disease: Clinical Features and Long-Term Outcome: A Case-Control Study of 8 Patients , 2010, Medicine.

[19]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[20]  Chengde Yang,et al.  Clinical Features and Prognosis of Adult-onset Still’s Disease: 61 Cases from China , 2009, The Journal of Rheumatology.

[21]  I. Kimber,et al.  Interleukin‐1‐induced interleukin‐6 synthesis is mediated by the neutral sphingomyelinase/Src kinase pathway in neurones , 2008, British journal of pharmacology.

[22]  L. Kanz,et al.  Anakinra in patients with treatment-resistant adult-onset Still's disease: four case reports with serial cytokine measurements and a review of the literature. , 2007, Seminars in arthritis and rheumatism.

[23]  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.

[24]  M. Dougados,et al.  Severe systemic inflammatory response syndrome in a patient with adult onset Still's disease treated with the anti-IL1 drug anakinra: a case report. , 2007, Clinical and experimental rheumatology.

[25]  G. Kalliolias,et al.  Anakinra treatment in patients with adult-onset Still’s disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial , 2007, Annals of the rheumatic diseases.

[26]  K. Eguchi,et al.  Adult Still's disease associated with cytomegalovirus infection , 2007, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[27]  A. Bakkaloğlu,et al.  A multicenter study of patients with adult-onset Still’s disease compared with systemic juvenile idiopathic arthritis , 2006, Clinical Rheumatology.

[28]  H. Nishino,et al.  Double-filtration plasmapheresis for resolution of corticosteroid resistant adult onset still's disease , 2006, Clinical Rheumatology.

[29]  P. Paik,et al.  Diagnosis and management of adult onset Still’s disease , 2005, Annals of the rheumatic diseases.

[30]  John P A Ioannidis,et al.  Heterogeneity testing in meta‐analysis of genome searches , 2005, Genetic epidemiology.

[31]  T. Hsieh,et al.  Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still's disease. , 2004, The Journal of rheumatology.

[32]  C. Suh,et al.  Serum cytokine profiles in patients with adult onset Still's disease. , 2003, The Journal of rheumatology.

[33]  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.

[34]  G. Burmester,et al.  Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. , 2003, Arthritis and rheumatism.

[35]  J. Piette,et al.  Proposal for a New Set of Classification Criteria for Adult-Onset Still Disease , 2002, Medicine.

[36]  O. Meyer,et al.  Corticosteroid sparing effect of low dose methotrexate treatment in adult Still's disease. , 1999, The Journal of rheumatology.

[37]  M. Kikuchi,et al.  Elevated serum interleukin 6, interferon-gamma, and tumor necrosis factor-alpha levels in patients with adult Still's disease. , 1998, The Journal of rheumatology.

[38]  T. Mimori,et al.  Methotrexate treatment in patients with adult onset Still’s disease—retrospective study of 13 Japanese cases , 1997, Annals of the rheumatic diseases.

[39]  A. Prost,et al.  Epidemiology of adult Still's disease: estimate of the incidence by a retrospective study in west France. , 1995, Annals of the rheumatic diseases.

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

[41]  M. Akizuki,et al.  Adult Still's disease: a multicenter survey of Japanese patients. , 1990, The Journal of rheumatology.

[42]  L. Cooperstein,et al.  Adult-onset Still's disease. Clinical course and outcome. , 1987, Arthritis and rheumatism.

[43]  Chang-Keun Lee,et al.  Clinical features and prognosis in 82 patients with adult-onset Still's disease. , 2014, Clinical and experimental rheumatology.

[44]  P. Voulgari,et al.  Adult-onset Still's disease: clinical, serological and therapeutic considerations. , 2013, Clinical and experimental rheumatology.

[45]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration , 2013 .

[46]  M. Iwamoto,et al.  Interleukin-18 in adult-onset Still's disease: treatment target or disease activity indicator? , 2012, Internal medicine.

[47]  L. Punzi,et al.  Adult-onset Still's disease with myocarditis successfully treated with the interleukin-1 receptor antagonist anakinra. , 2011, Joint, bone, spine : revue du rhumatisme.

[48]  N. Elomri,et al.  [Antagonists of interleukin-6 (tocilizumab), in adult refractory still disease]. , 2011, Presse medicale.

[49]  Ming-Fei Liu,et al.  Adult-onset Still's disease complicated with hemophagocytic syndrome. , 2010, Journal of the Formosan Medical Association = Taiwan yi zhi.

[50]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

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

[52]  Lee,et al.  Macrophage Activation Syndrome After Initiation of Corticosteroid and Etanercept in a Patient with Adult Onset Still ' s Disease , 2008 .

[53]  F. J. van der Woude,et al.  [Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in adult Still's disease]. , 2004, Deutsche Medizinische Wochenschrift.

[54]  W. Caspary,et al.  [Adult-onset Still's disease. Differential diagnosis in recurrent pharyngitis, fever of unknown original and excessive hyperferritinemia]. , 1999, Deutsche Medizinische Wochenschrift.

[55]  H. Chng,et al.  Adult-onset Still's disease in an oriental population: manifestations, course and outcome in 16 patients. , 1998, Annals of the Academy of Medicine, Singapore.

[56]  O. Meyer,et al.  [Fatal infectious complications in 2 patients with adult onset Still disease]. , 1996, La Revue de medecine interne.