Potential patient benefit of a subcutaneous formulation of tocilizumab for the treatment of rheumatoid arthritis: a critical review

Besada, Emilio

doi:10.2147/ppa.s34958

Cited by 7 publications

(2 citation statements)

References 37 publications

(195 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phase 3 randomized controlled trials demonstrated that i.v.-TCZ was an effective treatment for sJIA [ 14 ], pJIA [ 15 ] and RA [ 16 , 17 ]. In RA, s.c.-TCZ has efficacy and safety comparable with those of i.v.-TCZ [ 18 , 19 ]. S.c. injections offer a convenient alternative to i.v.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

et al. 2021

View full text Add to dashboard Cite

Objectives To determine subcutaneous-tocilizumab (SC-TCZ) dosing regimens for systemic juvenile idiopathic arthritis (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, SC-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or < 30 kg, respectively. Primary endpoints were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with intravenous-tocilizumab (IV-TCZ) in sJIA and pJIA. Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received SC-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with IV-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis Disease Activity Score-71 were comparable between SC-TCZ and IV-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of IV-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered related to TCZ. Conclusion SC-TCZ provides exposure and risk/benefit profiles similar to those of IV-TCZ. Subcutaneous administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, NCT01904292 and NCT01904279

show abstract

Section: Introductionmentioning

confidence: 99%

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Além disso, a taxa de mortalidade em pacientes com AR é duas a três vezes maior do que na população em geral, e a expectativa de vida é reduzida em 3 a 10 anos em razão da doença e dos eventos adversos (EA) relacionados ao tratamento (Besada, 2014;Alamanos & Drosos, 2005).…”

Section: Introductionunclassified

Análise de custo-efetividade de tocilizumabe como primeira linha de tratamento biológico para pacientes com artrite reumatoide, sob a perspectiva do Sistema Único de Saúde do Brasil

Matsumoto¹,

Valor²,

Rufino³

et al. 2016

JBES

View full text Add to dashboard Cite

Objetivo: A presente avaliação tem como finalidade determinar o custo-efetividade do tratamento de tocilizumabe em monoterapia como primeira linha de tratamento biológico em pacientes com artrite reumatoide (AR), sob a perspectiva do Sistema Único de Saúde do Brasil (SUS). Método: Foi elaborado um modelo de custo-efetividade com intuito de acompanhar os pacientes em tratamento após a falha de um medicamento modificador do curso da doença MMCD sintético, durante um horizonte de 24 semanas. O cenário-base avaliou a comparação direta de tocilizumabe versus adalimumabe, devido à existência de um estudo head-to-head. O cenário secundário avaliou tocilizumabe versus certolizumabe pegol e etanercepte indiretamente, por meio de uma metanálise de comparação indireta, devido à ausência de estudos head-to-head. A estimativa de custos médicos diretos totais para o tratamento de AR foi elaborada por opinião de especialistas e coletada de bases de dados secundárias. Resultados: O resultado do cenário-base do modelo evidenciou ganhos em efetividade com menor custo de tratamento, resultando em uma razão de custo-efetividade incremental (RCEI) dominante. O resultado do cenário secundário, comparação indireta, indicou que tocilizumabe foi mais eficaz que seus comparadores, sugerindo necessidade de investimento quando comparado a certolizumabe, que pode variar entre R$ 1.449,46 e R$ 18.934,62, e uma RCEI dominante quando comparado a etanercepte. Conclusão: A presente análise conclui que a monoterapia com tocilizumabe possui benefícios clínicos e econômicos no tratamento de AR, em pacientes que não podem manter a terapia com MMCD sintéticos e oferece alternativas aos sistemas de saúde no que se refere à alocação de recursos para sustentabilidade do sistema.

show abstract

Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active Neuromyelitis Optica Spectrum Disorder

et al. 2015

View full text Add to dashboard Cite

IMPORTANCE Neuromyelitis optica (NMO) is characterized by disabling relapses of optic neuritis and myelitis and the presence of aquaporin 4 antibodies (AQP4-abs). Interleukin 6, which is significantly elevated in serum and cerebrospinal fluid of patients with NMO, induces AQP4-ab production by plasmablasts and represents a novel therapeutic target.OBJECTIVE To evaluate the long-term safety and efficacy of tocilizumab, a humanized antibody targeting the interleukin 6 receptor, in NMO and NMO spectrum disorder. DESIGN, SETTING, AND PARTICIPANTSRetrospective observational study with 10 to 51 months of follow-up between December 2010 and February 2015, in neurology departments at tertiary referral centers. Participants were 8 female patients of white race/ethnicity with highly active AQP4-ab-seropositive NMO (n = 6) and NMO spectrum disorder (n = 2) whose disease had been resistant to previous medications, including B-cell depletion, and who switched to tocilizumab (6-8 mg/kg of body weight per dose). MAIN OUTCOMES AND MEASURESAnnualized relapse rate, Expanded Disability Status Scale score, spinal cord and brain magnetic resonance imaging, AQP4-ab titers, pain levels (numerical rating scale), and adverse effects. RESULTSPatients were followed up for a mean (SD) of 30.9 (15.9) months after switching to tocilizumab. Two of eight patients received add-on therapy with monthly corticosteroid pulses (temporary) or azathioprine, respectively. During tocilizumab treatment, the median annualized relapse rate significantly decreased from 4.0 (interquartile range, 3.0-5.0) in the year before tocilizumab therapy to 0.4 (interquartile range, 0.0-0.8) (P = .008), and the median Expanded Disability Status Scale score significantly decreased from 7.3 (interquartile range, 5.4-8.4) to 5.5 (interquartile range, 2.6-6.5) (P = .03). Active magnetic resonance imaging lesions were seen in 6 of 8 patients at tocilizumab initiation and in 1 of 8 patients at the last magnetic resonance imaging. Three patients remained relapse free during tocilizumab treatment. In 5 patients, a total of 8 relapses occurred, 4 within the first 2½ months of therapy. Five attacks were associated with delayed tocilizumab administration (Ն40 days), and 6 attacks were associated with reduced tocilizumab dosage (6 vs 8 mg/kg). The AQP4-ab titers (P = .02) and pain levels (P = .02) dropped significantly during tocilizumab treatment. Adverse effects included moderate cholesterol elevation in 6 of 8 patients, infections in 4 of 8 patients, and deep venous thrombosis and neutropenia in one patient each. CONCLUSIONS AND RELEVANCEProlonged tocilizumab therapy may be safe and effective from early treatment phases onward for otherwise therapy-resistant highly active NMO and NMO spectrum disorder. Relapse patterns indicate that adherence to a regular therapeutic regimen with monthly infusions of tocilizumab (8 mg/kg) may increase efficacy.

show abstract

Potential patient benefit of a subcutaneous formulation of tocilizumab for the treatment of rheumatoid arthritis: a critical review

Cited by 7 publications

References 37 publications

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis

Análise de custo-efetividade de tocilizumabe como primeira linha de tratamento biológico para pacientes com artrite reumatoide, sob a perspectiva do Sistema Único de Saúde do Brasil

Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active Neuromyelitis Optica Spectrum Disorder

Contact Info

Product

Resources

About