IL-6 Blockers in Systemic Onset Juvenile Idiopathic Arthritis

Barone, Patrizia; Pignataro, Rossana; Garozzo, Maria Teresa; Leonardi, ﻿Salvatore

doi:10.2217/imt.15.104

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…Because others have found evidence of increased production of proinflammatory cytokines such as IL-1, IL-6, IL-8, TGF-b1, and TNF-a on the ocular surface of KCS patients, [10][11][12]24 we hypothesized that topical tocilizumab treatment would decrease tear film and conjunctival mRNA levels of IL-6 and other inflammatory cytokines. [16][17][18][19] However, we found no significant differences between treated and control eyes in the majority of tear film cytokine levels or mRNA levels as determined from conjunctival biopsies (IFN-g, TNF-a, IL-1a, IL-1b, IL-2, IL-6, and IL-10) at the end of the treatment period. Interestingly, an unexpected finding was that there was a statistically significant difference in the level of IL-8 in treated eyes compared with untreated eyes at 4 weeks, and this difference decreased after treatment was stopped.…”

Section: Discussioncontrasting

confidence: 64%

“…15 Tocilizumab, a monoclonal antibody that inhibits the IL-6 receptor, 16,17 is an FDA-approved systemic medication for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. 18 Tocilizumab binds both the soluble (sIL-6R) and transmembrane IL-6 receptors (IL-6R), thereby blocking IL-6-mediated signal transduction. 19 Blockade of IL-6 on the ocular surface theoretically could result in decreased inflammation, thereby providing a novel strategy for the treatment of KCS.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tolerability of Topical Tocilizumab Eyedrops in Dogs: A Pilot Study

Bunya

Iwabe

Macchi

et al. 2017

Journal of Ocular Pharmacology and Therapeutics

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Tolerability of Topical Tocilizumab Eyedrops in Dogs: A Pilot Study

Bunya

Iwabe

Macchi

et al. 2017

Journal of Ocular Pharmacology and Therapeutics

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“… 15 , 16 , 52 , 53 It can be used alone or with MTX in children older than two. 29 , 62 In 2005, a Japanese study showed prompt response in 90% (10/11) of children with SJIA who were treated with tocilizumab. 52 Later, tocilizumab’s efficacy was confirmed in the RCT followed by a long-term open-label extension phase.…”

Section: Other Cytokine Blockers Effective In the Treatment Of Sjiamentioning

confidence: 99%

The role of IL-1 inhibition in systemic juvenile idiopathic arthritis: current status and future perspectives

Toplak¹,

Blazina²,

Avčin³

2018

DDDT

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The pathogenesis, clinical course, and response to treatment in systemic juvenile idiopathic arthritis (SJIA) differ from other types of juvenile idiopathic arthritis and are similar to other interleukin-1 (IL-1)-mediated diseases. The main cytokine involved in the pathogenesis of SJIA is IL-1β, which can be neutralized by targeted anti-IL-1 therapy. In SJIA, no antibodies have been found and there is growing evidence that it is mainly an autoinflammatory and not an autoimmune disease. Before the era of biologic therapy, treatment of SJIA was primarily based on long-term treatment with high doses of glucocorticosteroids (GCS). The side effects of GCS could have a significant impact on the outcome of the disease and could cause long-term damage. Treatment with anti-IL-1 agents early in the disease course has revolutionized the management principles of SJIA. However, not all SJIA patients respond equally well to anti-IL-1 therapy, and it has been shown that age at the onset of disease, duration of the disease, number of affected joints, neutrophil count, and ferritin level can predict the response to anti-IL-1 therapy. In particular, an elevated ferritin level should prompt testing for macrophage activation syndrome (MAS), the most severe complication of SJIA. Anti-IL-1 therapy has been shown to be effective also in patients with MAS. Although anti-IL-1 agents are currently not recommended as first-line treatment, there is growing evidence that anti-IL-1 agents introduced at the beginning of SJIA could enable lower doses and a shorter duration of GCS therapy, change the long-term disease outcome, and even influence molecular disease patterns. There are currently three anti-IL-1 agents available: anakinra, canakinumab, and rilonacept. In this review, we present the current knowledge on the pathogenesis of SJIA, the rational for anti-IL-1 treatment, and future perspectives on the treatment of SJIA.

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“…It is the first biological drug being approved for the treatment of sJIA in the European Union 2011 for use alone or in combination with methotrexate (MTX), in children older than 2 years. Its effectiveness treating children younger than 2 years is under investigation [ 13 ]. By 2013, the proportion of patients with sJIA who were treated with biologicals has increased to 20% in Germany [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

IL-6 blockade in systemic juvenile idiopathic arthritis – achievement of inactive disease and remission (data from the German AID-registry)

et al. 2018

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BackgroundSystemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting.MethodsIn 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) (https://aid-register.de). Data for this retrospective TCZ study were documented by 13 centers.ResultsFrom 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1–18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%.ConclusionOut of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%.Trial registrationThe AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

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IL-6 Blockers in Systemic Onset Juvenile Idiopathic Arthritis

Cited by 8 publications

References 49 publications

Tolerability of Topical Tocilizumab Eyedrops in Dogs: A Pilot Study

Tolerability of Topical Tocilizumab Eyedrops in Dogs: A Pilot Study

The role of IL-1 inhibition in systemic juvenile idiopathic arthritis: current status and future perspectives

IL-6 blockade in systemic juvenile idiopathic arthritis – achievement of inactive disease and remission (data from the German AID-registry)

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