Impact of tocilizumab administered intravenously or subcutaneously on patient-reported quality-of-life outcomes in patients with rheumatoid arthritis

Strand, Vibeke; Michalska, Margaret; Birchwood, Christine; Pei, Jinglan; Tuckwell, Katie; Finch, Rebecca; Kivitz, Alan; Smolen, Josef S.; Burmester, Gerd R

doi:10.1136/rmdopen-2017-000602

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…Virtually all treatments in RA will reduce fatigue, including conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), targeted synthetic DMARDs, biologic DMARDs and corticosteroids. 37 39–54 The average effect of treatment on fatigue in active RA with various advanced therapies is meaningful but not large. 39 Treatment of disease activity in RA has a small impact on fatigue, whereas physical inactivity, poor sleep and depressed mood explain most of the fatigue.…”

Section: Treatmentmentioning

confidence: 99%

Management of Fatigue in Rheumatoid Arthritis

Pope

2020

RMD Open

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Fatigue in rheumatoid arthritis is highly prevalent. It is correlated only weakly with disease activity but more so with pain, mood, personality features, poor sleep, obesity and comorbidities. Fatigue can be measured by many standardised questionnaires and more easily with a Visual Analogue Scale or numeric rating scale. Most patients with RA have some fatigue, and at least one in six have severe fatigue. Chronic pain and depressed mood are also common in RA patients with significant fatigue. It affects function and quality of life and is worse on average in women. Evidence-based treatment for fatigue includes treatment of underlying disease activity (with on average modest improvement of fatigue), exercise programmes and supervised self-management programmes with cognitive-behavioural therapy, mindfulness and reinforcement (such as reminders). The specific programmes for exercise and behavioural interventions are not standardised. Some medications cause fatigue such as methotrexate. More research is needed to understand fatigue and how to treat this common complex symptom in RA that can be the worst symptom for some patients.

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Section: Treatmentmentioning

confidence: 99%

Management of Fatigue in Rheumatoid Arthritis

Pope

2020

RMD Open

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“…In particular, the rates of MCID in TCZ and control groups were 50%–82% vs 31%–57% at week 16 in the OPTION study, and 54%–73% vs 42%–55% at week 12 in the BREVACTA study, respectively. Similarly, in the SUMMACTA trial, 24-week MCID was observed in 61%–84% and 64%– 84% of patients receiving IV or SC TCZ, respectively 116…”

Section: Introductionmentioning

confidence: 83%

“…The pivotal role of IL-6 in the development of RA systemic symptoms like pain, fatigue, and depression has been previously described 114. Two post hoc analyses evaluating the impact of TCZ on HRQOL (including patient global assessment [PtGA], pain, HAQ-DI, Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, and Short Form-36 [SF-36] physical [PCS] and mental [MCS] components) have been recently published 115,116…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient selection

Biggioggero¹,

Crotti²,

Becciolini³

et al. 2018

DDDT

115

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and systemic manifestations, such as anemia, fatigue, osteoporosis, and increased risk for cardiovascular diseases. The pathogenesis of RA is driven by a complex network of proinflammatory cytokines, with a pivotal role of IL-6 and tumor necrosis factor (TNF). The management of RA has been dramatically changed during the last years by the introduction of a treat-to-target approach aiming to achieve an acceptable disease control. Nowadays, TNF inhibitors (TNFis) are the most frequently prescribed class of biologic therapies, but the significant proportion of patients experiencing the failure of a TNFi led to the development of alternative therapeutic options targeted on different pathways. Considering the increasing number of targeted therapeutic options for RA, there is a growing interest in the identification of potential predictors of clinical response to each available mechanism of action, with the aim to drive the management of the disease toward a personalized approach according to the concept of precision medicine. Tocilizumab (TCZ) is the first humanized anti-IL-6 receptor subunit alpha (anti-IL-6R) monoclonal antibody approved for the treatment of RA refractory to methotrexate or TNFis. TCZ inhibits both the cis- and trans-signaling cascades involving the Janus kinase-signal transducer and the activator of transcription pathway, playing a crucial role in modulating not only joint inflammation but also the previously mentioned extra-articular manifestations and comorbidities of RA, such as fatigue, anemia, bone loss, depression, type 2 diabetes, and increased cardiovascular risk. In this review, moving from pathogenetic insights and evidence-based clinical data from randomized controlled trials and real-life observational studies, we will discuss the drivers for the selection of patient candidates to receive TCZ, in order to clarify the current positioning of this drug in the treatment algorithm of RA.

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“…SF-36, scores evaluated included physical and mental component summary (PCS, MCS) and domains: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). Minimum clinically important differences (MCID) for these endpoints were [32] 2.5 for PCS and MCS [33], 4.0 for FACIT [34,35], and 10.0 mm for AM-stiffness [21].…”

Section: Hrqol Endpointsmentioning

confidence: 99%

“…IL-6 levels also associate with a number of RA-related patient-reported outcomes (PRO), including fatigue and pain [11][12][13]. Studies of anti-IL-6R agents, such as tocilizumab [14][15][16][17][18][19][20][21] and sarilumab [22][23][24], in the treatment of moderate-to-severe RA have revealed the benefits of IL-6 inhibition, not only in the reduction of disease activity, but also improvement in pain and mood disorders associated with RA. The value of these clinical and PRO data notwithstanding, a formal association between IL-6 levels and overall health-related quality of life (HRQoL) in RA patients has not been investigated to date.…”

Section: Introductionmentioning

confidence: 99%

High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab

et al. 2020

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Background Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor α (anti-IL-6Rα) versus adalimumab, a tumor necrosis factor α inhibitor, both approved for treatment of active RA. Methods Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6–7.1 pg/mL), medium (7.2–39.5 pg/mL), and high (39.6–692.3 pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID). Results At baseline, patients with high versus medium or low IL-6 levels (n = 100, respectively) reported worse (nominal p < 0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p < 0.05). PCS improvements ≥MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p < 0.05). Adverse events between IL-6 tertiles were similar. Conclusions Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade. Trial registration NCT02332590. Registered on 5 January 2015

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Impact of tocilizumab administered intravenously or subcutaneously on patient-reported quality-of-life outcomes in patients with rheumatoid arthritis

Cited by 14 publications

References 22 publications

Management of Fatigue in Rheumatoid Arthritis

Management of Fatigue in Rheumatoid Arthritis

Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient selection

High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab

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