Subcutaneous Tocilizumab May Be Less Effective than Intravenous Tocilizumab in the Treatment of Juvenile Idiopathic Arthritis–associated Uveitis

Quesada-Masachs, Estefanía; Caballero, Consuelo Modesto

doi:10.3899/jrheum.160908

Cited by 39 publications

(19 citation statements)

References 9 publications

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“…Rapid disease control is important in uveitis, in which prolonged uveitis activity increases the risk of sight loss. 27 Subcutaneous tocilizumab was less effective than intravenous tocilizumab for juvenile idiopathic arthritis uveitis in a small case series, 28 but has shown similar efficacy to intravenous tocilizumab in randomised con trolled studies of rheumatoid arthritis. 29,30 Subcutaneous therapies are more desirable than intravenous infusions for patient convenience, maximising school attendance and using fewer healthcare resources.…”

Section: Resultsmentioning

confidence: 99%

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Ramanan

Dick

Guly

et al. 2020

The Lancet Rheumatology

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Background Uveitis associated with juvenile idiopathic arthritis is a cause of major ocular morbidity. A substantial proportion of children are refractory to systemic methotrexate and TNF inhibitors. Our aim was to study the safety and efficacy of tocilizumab in children with juvenile idiopathic arthritis-associated uveitis refractory to both methotrexate and TNF inhibitors. Methods This multicentre, single-arm, phase 2 trial was done following a Simon's two-stage design at seven tertiary hospital sites in the UK. Patients aged 2-18 years with active juvenile idiopathic arthritis-associated uveitis were eligible. All patients had been on a stable dose of methotrexate for at least 12 weeks and had not responded to treatment with a TNF inhibitor. Patients weighing 30 kg or more were treated with 162 mg subcutaneous tocilizumab every 2 weeks for 24 weeks, and participants weighing less than 30 kg were treated with 162 mg every 3 weeks for 24 weeks. The primary outcome was treatment response defined as a two-step decrease, or decrease to zero, from baseline in the level of inflammation (anterior chamber cells) at week 12, per the standardisation of uveitis nomenclature criteria. A phase 3 trial would be justified if more than seven patients responded to treatment. An interim analysis was planned to assess whether the trial would be stopped for futility, with futility defined as two or fewer treatment responses among ten participants. Adverse events were collected up to 30 calendar days after treatment cessation. The primary analysis was done in the intention-to-treat population and the safety analysis was done in all patients who started the treatment. This trial is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN95363507) and EU Clinical Trials Register (EudraCT 2015-001323-23). Findings 22 participants were enrolled to the trial between Dec 3, 2015, and March 9, 2018, and 21 participants received treatment. One participant was found to be ineligible immediately after enrolment and was therefore withdrawn. Seven of 21 (median unbiased estimate of proportion 34% [95% CI 25-57]) responded to treatment (p=0•11). Safety results were consistent with the known safety profile of tocilizumab. Interpretation The primary endpoint was not met, and thus the results do not support a phase 3 trial of tocilizumab in patients with juvenile idiopathic arthritis-associated uveitis. Importantly, data on the use of tocilizumab in clinical practice is now captured in national registries. Despite this trial not meeting the threshold required to justify a larger phase 3 trial, several patients responded to treatment; as such, tocilzumab might still be a therapeutic option in some children with uveitis refractory to anti-TNF drugs, given the absence of other treatment options.

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Section: Resultsmentioning

confidence: 99%

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Ramanan

Dick

Guly

et al. 2020

The Lancet Rheumatology

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“…However, serious complications including severe autoimmune thrombocytopenia and pneumonia have been reported. A recent study described four patients with long-term, JIA-associated chronic anterior uveitis who exhibited good sustained responses on intravenous tocilizumab [63]. However, they experienced early flares after switching to subcutaneous tocilizumab.…”

Section: Resultsmentioning

confidence: 99%

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review

et al. 2018

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Tocilizumab, an anti-interleukin-6 (IL-6) agent, is indicated as a treatment for several autoimmune or inflammatory diseases, including rheumatoid arthritis and juvenile idiopathic arthritis (JIA). IL-6 plays roles in both immune system dysregulation and inflammation, and thus efforts to extend the utility of tocilizumab in patients with autoinflammatory conditions are ongoing. Here, we survey the literature on the off-label use of tocilizumab in patients with juvenile-onset rheumatic diseases including juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis (DM), vasculitis, juvenile scleroderma, and other autoinflammatory diseases. There is no real evidence that tocilizumab is useful for patients with SLE and juvenile DM, but several cases of childhood Takayasu arteritis have experienced promising outcomes. In juvenile-onset scleroderma, for which no therapy that can halt disease progression is available, tocilizumab may stop progression and the associated functional impairment. Tocilizumab prevents systemic inflammation in patients with Kawasaki’s disease, but may develop coronary aneurysms. Tocilizumab has been used to treat several pediatric autoinflammatory diseases, including JIA-associated uveitis and Castleman’s disease. Further work in larger populations is necessary to confirm the effects of tocilizumab in patients with pediatric rheumatic diseases.

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“…TOC is licensed for the treatment of juvenile idiopathic arthritis (JIA) in both systemic (13) and polyarticular subtypes (14). It has also shown a promising effect in JIA-related uveitis (15–16–17). Based on the promising TOC data on skin involvement in adult systemic sclerosis studies (7), the hypothesized effect of TOC to mediate enhanced degradation of the extracellular matrix (18), as well as the proven good tolerability in children with JIA, TOC seems to be a promising option for treatment-resistant jlSc patients.…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab is a promising treatment option for therapy resistant juvenile localized scleroderma patients

Foeldvari

Antón

Friswell

et al. 2017

Journal of Scleroderma and Related Disorders

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ORIGINAL RESEARCH ARTICLE blind, controlled trial (3), around 67% of patients with jlSc responded to treatment with methotrexate. In subsequent studies, albeit with small numbers of patients, mycophenolate appeared to be an option in methotrexate nonresponse or intolerance cases (4, 5). Based on adult studies on patients with systemic sclerosis, abatacept (6), tocilizumab (TOC) (6, 7), and rituximab (8, 9) appear to have a beneficial effect on skin involvement. Further studies in patients with localized scleroderma using rituximab and abatacept have been reported. Abatacept showed promising effects in 5 patients (10, 11), and rituximab was tried in one patient (12). TOC is licensed for the treatment of juvenile idiopathic arthritis (JIA) in both systemic (13) and polyarticular subtypes (14). It has also shown a promising effect in JIA-related uveitis (15-17). Based on the promising TOC data on skin involvement in adult systemic sclerosis studies (7), the hypothesized effect of TOC to mediate enhanced degradation of the extracellular matrix (18), as well as the proven good tolerability in children with JIA, TOC seems to be a promising option for treatment-resistant jlSc patients. In a recent review of novel

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Subcutaneous Tocilizumab May Be Less Effective than Intravenous Tocilizumab in the Treatment of Juvenile Idiopathic Arthritis–associated Uveitis

Cited by 39 publications

References 9 publications

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Tocilizumab in patients with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis (APTITUDE): a multicentre, single-arm, phase 2 trial

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review

Tocilizumab is a promising treatment option for therapy resistant juvenile localized scleroderma patients

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