Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey

Roodenrijs, Nadia M T; Hair, Maria J. H. de; Goes, Marlies C van der; Jacobs, Johannes W. G.; Welsing, Paco M J; Heijde, Desirée van der; Aletaha, Daniel; Dougados, Maxime; Hyrich, Kimme L; McInnes, Iain B.; Müeller-Ladner, Ulf; Šenolt, Ladislav; Szekanecz, Zoltán; Laar, Jacob M van; Nagy, György

doi:10.1136/annrheumdis-2018-213687

Cited by 92 publications

(91 citation statements)

References 7 publications

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“…With advances in the treatment of RA, optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice [8,9]. Although the global consensus is that there is a wide variation in difficult-totreat statuses, few studies have stratified the patients by response patterns.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that a high education level [12], low disability grade [13,14] and usages of nonsteroidal anti-inflammatory drugs [13] and methotrexate (MTX) [15][16][17] are associated with a good response to TNFis, whereas a young age [18], obesity [19], smoking [20], high disease activity at the time of treatment [13], glucocorticoid usage [12,18] and positivity for rheumatoid factor (RF) and anti-citrullinated protein (CCP) antibodies [18,21] are associated with a poor response. However, these findings have not always been consistent across studies [8]. As a result, the choice of treatment usually depends on the route of administration, dose interval, chemical structure and cost rather than etiological factors.…”

Section: Introductionmentioning

confidence: 90%

“…Even so, 20-30% of patients with RA remain refractory to treatment [4][5][6], and only half of patients treated with any single agent have a major benefit [7]. Refractory RA involves a variety of concepts [8]: thus far, the definition of this status is arbitrary, and data on the outcomes of these patients remain limited [9]. From a clinical viewpoint, the refractory status of RA can be roughly categorised into three groups: insensitivity, in which no improvement is observed from the start of treatment; secondary refractory, in which partial, but insufficient, improvement is evident; and false refractory, in which patients complain persistent pain though inflammation is absent [9].…”

Section: Introductionmentioning

confidence: 99%

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Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

et al. 2020

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Background: With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs. Methods: This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints-C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group. Results: Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity. Conclusions: In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

et al. 2020

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“…In this study, cNR patients had significantly higher baseline and 6-month ccIMT, as well as baseline PWV. cNR patients may reflect a more severe, difficult-to-treat subset of arthritis patients [40]. Sustained inflammation and clinical activity associated with clinical non-response to treatment drives accelerated atherosclerosis in RA and AS [1][2][3]8].…”

Section: Discussionmentioning

confidence: 99%

Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

et al. 2019

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Accelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

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“…Moreover, the existence of patients with di cult-to-treat RA [4], who ultimately become resistant to multitypes of DMARDs, raises requirement of understanding about molecular status of remission.…”

Section: Introductionmentioning

confidence: 99%

Molecular Remission at T cell level in Patients with Rheumatoid Arthritis

Inamo

Suzuki

Takeshita

et al. 2020

Preprint

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Background: While numerous disease-modifying anti-rheumatic drugs (DMARDs) has brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain such as small proportion of achievement drug-free patients. The aim of this study is to explore key molecules for remission at T cell level, which is known to involve the pathogenesis of RA deeply, and investigate disease course of patients who achieved molecular remission (MR). Methods: We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4 + T cells and CD8 + T cells of patients with RA using machine learning methods. In addition, we investigated the benefit of achieving MR on disease control thereafter. Results: We identified 9 and 23 genes that were associated with clinical remission in CD4 + and CD8 + T cells. Principal component analysis (PCA) demonstrated expression profiling of them was similar with HCs. As to remission signature genes in CD4 + T cells, PCA result was reproduced using validation cohort, indicating their robustness. There was a trend towards better disease control during 12 months follow-up in patients treated with tocilizumab in deep MR than those in non-deep MR, although it was not significant. Conclusion: We identified robust genes which represented remission status in CD4 + T cells using machine learning techniques. The current study will promote our understandings about molecular mechanism to achieve deep remission in the management of RA.Trial registration: Not required.

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Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey

Abstract: There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations.

Cited by 92 publications

References 7 publications

Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

Molecular Remission at T cell level in Patients with Rheumatoid Arthritis

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