Published online Sep 18, 2024. doi: 10.5312/wjo.v15.i9.831
Revised: July 27, 2024
Accepted: August 19, 2024
Published online: September 18, 2024
Processing time: 169 Days and 5.7 Hours
A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs (NSAIDs) for juvenile idiopathic arthritis (JIA). Herein, we outline the progress in drug therapy of JIA. NSAIDs have traditionally been the primary treatment for all forms of JIA. NSAIDs are symptom-relief medications, and well tolerated by patients. Additionally, the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs. Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect. However, the frequent adverse events limit the clinical use. Both NSAIDs and glucocorticoid fail to ease or pre
Core Tip: In past decades, the pharmacological treatments for juvenile idiopathic arthritis (JIA) have undergone a dramatic evolution from non-steroidal anti-inflammatory drugs to disease-modifying antirheumatic drugs (DMARDs), especially the emergence of biologic DMARDs enable patients with refractory JIA to achieve disease remission. This editorial focuses on the progress in treatment options for JIA. We hope that this editorial could provide valuable information for use of anti-JIA drugs.
- Citation: Ren T, Guan JH, Li Y, Li NN, Li Z. Evolution of treatment options for juvenile idiopathic arthritis. World J Orthop 2024; 15(9): 831-835
- URL: https://www.wjgnet.com/2218-5836/full/v15/i9/831.htm
- DOI: https://dx.doi.org/10.5312/wjo.v15.i9.831
Juvenile idiopathic arthritis (JIA) refers to a broad term characterizing all forms of arthritis occurred in children before 16 years of age. JIA is a common autoimmune disease and a leading cause of childhood disability[1]. As a heterogeneous group of arthritis, JIA may subside with age, or, often extend chronic disease and inflammation of the joints throughout middle age in a significant proportion of patients[2,3]. Clinical manifestations of JIA include joint pain, swelling and stiffness. Moreover, it usually accompanies other systemic symptoms of flaccid fever, rash, and enlargement of liver, spleen and lymph nodes[4,5].
The goal of treatment is to control disease activity and prevent complications. Current treatment options include non-pharmacological and pharmacological interventions. Non-pharmacological interventions, such as psychological rehabilitation and exercise, are indispensable and helpful to foster the normal psychosocial and social development of the child and to keep or restore joint function and normal mobility[6,7]. Pharmacological interventions are the mainstay in the management of JIA. The therapeutic strategies have evolved markedly, owing to the availability of a growing number of specific and potent medications. Herein, we specifically discuss the progress of pharmacological treatments for JIA.
Non-steroidal anti-inflammatory drugs (NSAIDs) have traditionally been the mainstay treatment for all forms of JIA. Although the era of biological targeted therapy comes, NSAIDs are still suggested as first-line therapy[8]. NSAIDs work by blocking cyclooxygenase (COX) synthesis to exert analgesic and anti-inflammatory effects[9]. They can alleviate joint pain, swelling, stiffness and fever, but have no effects on joint damage. NSAIDs are well tolerated by children with few side-effects. Moreover, the availability of COX-2 selective inhibitors further lowers the adverse reactions compared with traditional NSAIDs[10]. The most common traditional NSAIDs for JIA include naproxen and ibuprofen, while celecoxib and rofecoxib are frequently used selective NSAIDs[11]. However, the comparative effectiveness and safety between different NSAIDs remains inconclusive. Although two studies suggested the superiority of celecoxib in effectiveness and rofecoxib in safety over other NSAIDs[12,13], these findings still need to be confirmed by solid evidence. Noticeably, the duration of NSAID monotherapy for more than 2 months is discouraged if arthritis is still active[14].
Glucocorticoid is another kind of symptom-relief medication that can exert rapid and potent anti-inflammatory effect. Glucocorticoid is necessary when NSAIDs fail to provide desired efficacy. Intra-articular injection of glucocorticoid is the main treatment for monoarticular or oligoarticular JIA without systemic symptoms[15]. This topical therapy is very helpful for preventing deformities that occur after chronic arthritis. Triamcinolone hexacetonide is preferred for intra-articular injection, since it offers a more durable clinical response than the other available glucocorticoids[16]. Systemic glucocorticoid is usually restricted to systemic JIA with extra-articular manifestations[7]. Prednisone is often the drug of choice for oral administration. However, the adverse events (e.g., growth retardation, infection, and osteoporosis) limit the prolonged use of glucocorticoid at large dose[17].
Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are usually used in the initial therapy of polyarthritis, and in the case of inadequate efficacy from first-line treatment for oligo-arthritis[16]. The introduction of methotrexate (MTX) was a significant milestone in csDMARDs[18]. MTX exerts long-acting anti-inflammatory effects mainly through inhibition of interleukin (IL)-1 production[19]. Owing to its sustained effectiveness and acceptable toxicity, MTX remains the first choice second-line drug for JIA that is not controlled by NSAIDs or intra-articular corticosteroid injection[20,21]. Noticeably, prolonging MTX administration for 12 months did not yield additional benefit after the achievement of disease remission by 6 months treatment[22]. The other commonly used csDMARDs include sulfasalazine, lefunomide and cyclophosphamide, and they produce anti-inflammatory effects through different mechanisms. Leflunomide is less effective than MTX[23], but it is still an effective treatment for patients with MTX intolerance[24]. In addition, sulfasalazine is often the csDMARD of choice in patients with enthesitis-related arthritis[25].
The pharmacological therapeutics for JIA are still evolving, in which biologic DMARDs (bDMARDs) represent the most active and revolutionary field. bDMARDs are mainly selective inhibitors targeting one of three major pro-inflammatory cytokines (TNF, IL-1β, and IL-6). The other newly developed agents include anti-T cell-specific inhibitors, CD20 monoclonal antibodies, and Janus kinase (JAK) inhibitors. They are usually given along with MTX to patients who have an inadequate response to MXT alone.
The first bDMARD introduced to the treatment of JIA is etanercept, a recombinant human TNF-α receptor antagonist. Subsequently, other anti-TNF drugs were developed, such as infliximab, adalimumab, golimumab and certolizumab. Etanercept has been demonstrated the sustained benefits in growth velocity, bone status, and quality of life, and achieving complete disease quiescence in half of the patients[26-28]. Adalimumab is found to be highly effective in patients with or without previous treatment by other biologic agents[29]. Moreover, adalimumab achieves higher response rate than infiximab which is not approved for use in JIA[30]. Golimumab fails to exert superior efficacy over placebo in a trial and it has not yet been approved for use in JIA[31]. Certolizumab is still being evaluated by an ongoing trial. Of these drugs, only etanercept and adalimumab are authorized for use in JIA by both the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Other bDMARDs that have been approved to be effective in MTX-resistant JIA include IL-1 inhibitors and IL-6 inhibitors. Canakinumab, an IL-1 inhibitor, has been approved by FDA and EMA for use in systemic JIA[32], while Tocilizumab, a monoclonal antibody against IL-6 receptor, has been approved for use in both polyarticular and systemic JIA[33,34]. Unlike the key role of TNF-α in polyarticular JIA, increasing evidence suggests that the major pathogenic cytokines in active systemic JIA are IL-1 and IL-6[35,36]. Patients with the systemic subtype of JIA generally respond well to an IL-1 inhibitor or IL-6 inhibitor, whereas an anti-TNF agent could be less effective in this subtype.
Abatacept is a selective T-cell activation blocker by targeting cytotoxic T-lymphocyte-associated antigen-4. The efficacy and safety of abatacept in JIA have been evidenced by a double-blind randomized controlled withdrawal trial, and then it is approved in the United States and Europe for JIA[37]. Rituximab is a human mouse chimeric monoclonal antibody targeting B lymphocyte (CD20). It is recommended for children with JIA who remain highly or moderately active with poor prognostic factors after sequential treatment with anti-TNF drugs and abatacept[38]. Besides, some newer drugs have been developed for the treatment of JIA, mainly JAK inhibitors, e.g., tofacitinib[39], baricitinib[40] and ruxolitinib[41]. Their efficacy and safety have been established in randomized controlled trials, and some of them have already been approved for use in JIA.
Huge progress has been achieved in available medications and treatment recommendations. The pharmacological treatments have undergone a dramatic evolution from NSAIDs to DMARDs, especially bDMARDs. Although treatment of JIA remains difficult, new treatments offer valuable opportunities for some patients with refractory JIA.
1. | Zaripova LN, Midgley A, Christmas SE, Beresford MW, Baildam EM, Oldershaw RA. Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol Online J. 2021;19:135. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 88] [Cited by in F6Publishing: 79] [Article Influence: 26.3] [Reference Citation Analysis (0)] |
2. | d'Angelo DM, Di Donato G, Breda L, Chiarelli F. Growth and puberty in children with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2021;19:28. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 23] [Article Influence: 7.7] [Reference Citation Analysis (0)] |
3. | Selvaag AM, Aulie HA, Lilleby V, Flatø B. Disease progression into adulthood and predictors of long-term active disease in juvenile idiopathic arthritis. Ann Rheum Dis. 2016;75:190-195. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 106] [Cited by in F6Publishing: 125] [Article Influence: 12.5] [Reference Citation Analysis (0)] |
4. | Mahmud SA, Binstadt BA. Autoantibodies in the Pathogenesis, Diagnosis, and Prognosis of Juvenile Idiopathic Arthritis. Front Immunol. 2018;9:3168. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 33] [Cited by in F6Publishing: 47] [Article Influence: 9.4] [Reference Citation Analysis (0)] |
5. | Kim JW, Ahn MH, Jung JY, Suh CH, Kim HA. An Update on the Pathogenic Role of Neutrophils in Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease. Int J Mol Sci. 2021;22. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3] [Cited by in F6Publishing: 16] [Article Influence: 5.3] [Reference Citation Analysis (0)] |
6. | Häfner R, Truckenbrodt H, Spamer M. Rehabilitation in children with juvenile chronic arthritis. Baillieres Clin Rheumatol. 1998;12:329-361. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23] [Cited by in F6Publishing: 23] [Article Influence: 0.9] [Reference Citation Analysis (0)] |
7. | Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2006;20:279-300. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 47] [Cited by in F6Publishing: 51] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
8. | Bansal N, Pasricha C, Kumari P, Jangra S, Kaur R, Singh R. A comprehensive overview of juvenile idiopathic arthritis: From pathophysiology to management. Autoimmun Rev. 2023;22:103337. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
9. | Miller LG, Prichard JG. Current issues in NSAID therapy. Prim Care. 1990;17:589-601. [PubMed] [Cited in This Article: ] |
10. | Zhao WJ, Deng JH, Li CF. Research progress in drug therapy of juvenile idiopathic arthritis. World J Pediatr. 2022;18:383-397. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1] [Cited by in F6Publishing: 2] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
11. | Giancane G, Consolaro A, Lanni S, Davì S, Schiappapietra B, Ravelli A. Juvenile Idiopathic Arthritis: Diagnosis and Treatment. Rheumatol Ther. 2016;3:187-207. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 97] [Cited by in F6Publishing: 110] [Article Influence: 13.8] [Reference Citation Analysis (0)] |
12. | Shi CL, Zhang Y, Zhang ZY, Zhou J, Tang XM. Comparative Efficacy and Safety of Non-Steroidal Anti-Inflammatory Drugs in Patients With Juvenile Idiopathic Arthritis: A Systematic Review and Network Meta-analysis. Indian Pediatr. 2021;58:162-168. [PubMed] [Cited in This Article: ] |
13. | Zeng T, Ye JZ, Qin H, Xu QQ. Systematic review and network meta-analysis of different non-steroidal anti-inflammatory drugs for juvenile idiopathic arthritis. World J Clin Cases. 2024;12:2056-2064. [PubMed] [DOI] [Cited in This Article: ] [Reference Citation Analysis (0)] |
14. | Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Martini A, Rabinovich CE, Ruperto N. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011;63:465-482. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 608] [Cited by in F6Publishing: 525] [Article Influence: 40.4] [Reference Citation Analysis (0)] |
15. | Scott C, Meiorin S, Filocamo G, Lanni S, Valle M, Martinoli C, Martini A, Ravelli A. A reappraisal of intra-articular corticosteroid therapy in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2010;28:774-781. [PubMed] [Cited in This Article: ] |
16. | Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angeles-Han ST, Becker ML, Cron RQ, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Kimura Y, Lee T, Murphy K, Nigrovic PA, Ombrello MJ, Rabinovich CE, Tesher M, Twilt M, Klein-Gitelman M, Barbar-Smiley F, Cooper AM, Edelheit B, Gillispie-Taylor M, Hays K, Mannion ML, Peterson R, Flanagan E, Saad N, Sullivan N, Szymanski AM, Trachtman R, Turgunbaev M, Veiga K, Turner AS, Reston JT. 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2022;74:553-569. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 71] [Article Influence: 35.5] [Reference Citation Analysis (0)] |
17. | Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369:767-778. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 983] [Cited by in F6Publishing: 969] [Article Influence: 57.0] [Reference Citation Analysis (0)] |
18. | Giannini EH, Brewer EJ, Kuzmina N, Shaikov A, Maximov A, Vorontsov I, Fink CW, Newman AJ, Cassidy JT, Zemel LS. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. N Engl J Med. 1992;326:1043-1049. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 432] [Cited by in F6Publishing: 359] [Article Influence: 11.2] [Reference Citation Analysis (0)] |
19. | Solebo AL, Rahi JS, Dick AD, Ramanan AV, Ashworth J, Edelsten C; Members of the POIG Uveitis Delphi Group. Areas of agreement in the management of childhood non-infectious chronic anterior uveitis in the UK. Br J Ophthalmol. 2020;104:11-16. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 9] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
20. | Raab A, Kallinich T, Huscher D, Foeldvari I, Weller-Heinemann F, Dressler F, Kuemmerle-Deschner JB, Klein A, Horneff G. Outcome of children with oligoarticular juvenile idiopathic arthritis compared to polyarthritis on methotrexate- data of the German BIKER registry. Pediatr Rheumatol Online J. 2021;19:41. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2] [Cited by in F6Publishing: 3] [Article Influence: 1.0] [Reference Citation Analysis (0)] |
21. | Bakry R, Klein MA, Horneff G. Oral or Parenteral Methotrexate for the Treatment of Polyarticular Juvenile Idiopathic Arthritis. Eur J Rheumatol. 2022;9:197-205. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 2] [Reference Citation Analysis (0)] |
22. | Foell D, Wulffraat N, Wedderburn LR, Wittkowski H, Frosch M, Gerss J, Stanevicha V, Mihaylova D, Ferriani V, Tsakalidou FK, Foeldvari I, Cuttica R, Gonzalez B, Ravelli A, Khubchandani R, Oliveira S, Armbrust W, Garay S, Vojinovic J, Norambuena X, Gamir ML, García-Consuegra J, Lepore L, Susic G, Corona F, Dolezalova P, Pistorio A, Martini A, Ruperto N, Roth J; Paediatric Rheumatology International Trials Organization (PRINTO). Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA. 2010;303:1266-1273. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 201] [Cited by in F6Publishing: 189] [Article Influence: 13.5] [Reference Citation Analysis (0)] |
23. | Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P, Horneff G, Calvo I, Szer IS, Simpson K, Stewart JA, Strand V; Leflunomide in Juvenile Rheumatoid Arthritis (JRA) Investigator Group. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med. 2005;352:1655-1666. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 178] [Cited by in F6Publishing: 124] [Article Influence: 6.5] [Reference Citation Analysis (0)] |
24. | Ayaz NA, Karadağ ŞG, Çakmak F, Çakan M, Tanatar A, Sönmez HE. Leflunomide treatment in juvenile idiopathic arthritis. Rheumatol Int. 2019;39:1615-1619. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 9] [Cited by in F6Publishing: 6] [Article Influence: 1.2] [Reference Citation Analysis (0)] |
25. | Ringold S, Angeles-Han ST, Beukelman T, Lovell D, Cuello CA, Becker ML, Colbert RA, Feldman BM, Ferguson PJ, Gewanter H, Guzman J, Horonjeff J, Nigrovic PA, Ombrello MJ, Passo MH, Stoll ML, Rabinovich CE, Schneider R, Halyabar O, Hays K, Shah AA, Sullivan N, Szymanski AM, Turgunbaev M, Turner A, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Rheumatol. 2019;71:846-863. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 96] [Article Influence: 19.2] [Reference Citation Analysis (0)] |
26. | Giannini EH, Ilowite NT, Lovell DJ, Wallace CA, Rabinovich CE, Reiff A, Higgins G, Gottlieb B, Chon Y, Zhang N, Baumgartner SW. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3259-3264. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 45] [Cited by in F6Publishing: 49] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
27. | Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, Wouters CH. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49:1550-1558. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 42] [Cited by in F6Publishing: 44] [Article Influence: 3.1] [Reference Citation Analysis (0)] |
28. | Solari N, Palmisani E, Consolaro A, Pistorio A, Viola S, Buoncompagni A, Gattorno M, Picco P, Ruperto N, Malattia C, Martini A, Ravelli A. Factors associated with achievement of inactive disease in children with juvenile idiopathic arthritis treated with etanercept. J Rheumatol. 2013;40:192-200. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 39] [Cited by in F6Publishing: 40] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
29. | Schmeling H, Minden K, Foeldvari I, Ganser G, Hospach T, Horneff G. Efficacy and safety of adalimumab as the first and second biologic agent in juvenile idiopathic arthritis: the German Biologics JIA Registry. Arthritis Rheumatol. 2014;66:2580-2589. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 56] [Cited by in F6Publishing: 63] [Article Influence: 6.3] [Reference Citation Analysis (0)] |
30. | Cecchin V, Zannin ME, Ferrari D, Pontikaki I, Miserocchi E, Paroli MP, Bracaglia C, Marafon DP, Pastore S, Parentin F, Simonini G, De Libero C, Falcini F, Petaccia A, Filocamo G, De Marco R, La Torre F, Guerriero S, Martino S, Comacchio F, Muratore V, Martini G, Vittadello F, Zulian F. Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis. J Rheumatol. 2018;45:1167-1172. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 39] [Cited by in F6Publishing: 50] [Article Influence: 8.3] [Reference Citation Analysis (0)] |
31. | Brunner HI, Ruperto N, Tzaribachev N, Horneff G, Chasnyk VG, Panaviene V, Abud-Mendoza C, Reiff A, Alexeeva E, Rubio-Pérez N, Keltsev V, Kingsbury DJ, Del Rocio Maldonado Velázquez M, Nikishina I, Silverman ED, Joos R, Smolewska E, Bandeira M, Minden K, van Royen-Kerkhof A, Emminger W, Foeldvari I, Lauwerys BR, Sztajnbok F, Gilmer KE, Xu Z, Leu JH, Kim L, Lamberth SL, Loza MJ, Lovell DJ, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial. Ann Rheum Dis. 2018;77:21-29. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 72] [Cited by in F6Publishing: 83] [Article Influence: 11.9] [Reference Citation Analysis (0)] |
32. | Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2396-2406. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 515] [Cited by in F6Publishing: 483] [Article Influence: 40.3] [Reference Citation Analysis (0)] |
33. | Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Pérez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gámir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F; Paediatric Rheumatology International Trials Organisation PRINTO; Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74:1110-1117. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 209] [Cited by in F6Publishing: 193] [Article Influence: 19.3] [Reference Citation Analysis (0)] |
34. | De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A; PRINTO; PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2385-2395. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 608] [Cited by in F6Publishing: 577] [Article Influence: 48.1] [Reference Citation Analysis (0)] |
35. | De Benedetti F, Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J Rheumatol. 1998;25:203-207. [PubMed] [Cited in This Article: ] |
36. | 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;201:1479-1486. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 686] [Cited by in F6Publishing: 654] [Article Influence: 34.4] [Reference Citation Analysis (0)] |
37. | Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio-Pérez N, Silva CA, Abud-Mendoza C, Burgos-Vargas R, Gerloni V, Melo-Gomes JA, Saad-Magalhães C, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Orozco J, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace CA, Sigal LH, Block AJ, Covucci A, Martini A, Giannini EH; Paediatric Rheumatology INternational Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372:383-391. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 388] [Cited by in F6Publishing: 334] [Article Influence: 20.9] [Reference Citation Analysis (0)] |
38. | Takakura M, Shimizu M, Mizuta M, Inoue N, Tasaki Y, Ohta K, Furuichi K, Wada T, Yachie A. Successful treatment of rituximab- and steroid-resistant nephrotic syndrome with leukocytapheresis. J Clin Apher. 2018;33:409-411. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 2] [Cited by in F6Publishing: 2] [Article Influence: 0.3] [Reference Citation Analysis (0)] |
39. | Huang Z, Lee PY, Yao X, Zheng S, Li T. Tofacitinib Treatment of Refractory Systemic Juvenile Idiopathic Arthritis. Pediatrics. 2019;143. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 29] [Cited by in F6Publishing: 34] [Article Influence: 6.8] [Reference Citation Analysis (0)] |
40. | Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich C, Rooney T, Schlichting D, Macias WL, de Bono S, Tanaka Y. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017;376:652-662. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 520] [Cited by in F6Publishing: 555] [Article Influence: 79.3] [Reference Citation Analysis (0)] |
41. | Bader-Meunier B, Hadchouel A, Berteloot L, Polivka L, Béziat V, Casanova JL, Lévy R. Effectiveness and safety of ruxolitinib for the treatment of refractory systemic idiopathic juvenile arthritis like associated with interstitial lung disease: a case report. Ann Rheum Dis. 2022;81:e20. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 28] [Article Influence: 7.0] [Reference Citation Analysis (0)] |