Defining remission in rheumatoid arthritis: does it matter to the patient? A comparison of multi-dimensional remission criteria and patient reported outcomes

Gul, Hanna; Eugenio, Gisella; Rabin, Thibault; Burska, Agata; Parmar, Rekha; Wu, Jianhua; Ponchel, Frédérique; Emery, Paul

doi:10.1093/rheumatology/kez330

Cited by 20 publications

(27 citation statements)

References 32 publications

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“…We have previously reported that when patients received steroids >3 months before their baseline visit at the IA-stage of the continuum, there was no impact on the distribution of T-cell subset frequencies 25 nor was there any significant difference in whole blood lymphocyte counts between any of the groups (data not shown).…”

Section: Quantification Of T-cell Subsetsmentioning

confidence: 89%

“…Despite low sensitivity, the high specificity of abnormal naïve T-cells (confirmed by regression modelling) allows identification of patients who should not taper therapy. Further study of the depth of remission need to be performed to assess the sustainability of remission over 12 months notably when on b-DMARDs., Recent data showing that 25-30% of patients with DMARD induced remission, present with reduced naïve cells indicates the potential of this approach 25 .…”

Section: Discussionmentioning

confidence: 99%

“…The latter being calculated from the age-subset frequency correlation observed in 120 healthy control. Because this not a statistical correction but a practical variable normalisation allowing to use positive vs negative parameters, we have changed wording (previously used in publications) to use "normalised %": where [Normalised %] = [frequency (%) observed in patient] -[frequency (%) expected at that age] as described recently 25 .…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…Having previously demonstrated the age relationship between naïve and Treg cells in health (depicted in Fig. 1, panel b using 120 HC), frequencies observed in patients were normalised for age as described 22,24,25 (see also supplementary material). IRC frequencies were independent of age and dichotomised using the top of the 95% CI range in heathy control (+4%).…”

Section: Quantification Of T-cell Subsetsmentioning

confidence: 97%

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T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

Ponchel

Burska

Hunt

et al. 2020

Sci Rep

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The presence of a disease continuum in inflammatory arthritis (IA) is a recognised concept, with distinct stages from at-risk stage (presence of anti citrullinated-peptide autoantibody) to diagnosis of rheumatoid arthritis (RA), including therapy-induced remission. Despite T-cell dysregulation being a key feature of RA, there are few reports of T-cell phenotyping along the IA-continuum. We investigated the disturbances of naïve, regulatory and inflammation related cell (IRC) CD4+ T-cell subsets in 705 individuals across the IA-continuum, developing a simple risk-score (summing presence/absence of a risk-associated with a subset) to predict progression from one stage to the next. In 158 at-risk individuals, the 3 subsets had individual association with progression to IA and the risk-score was highly predictive (p < 0.0001). In evolving IA patients, 219/294 developed RA; the risk-score included naïve and/or Treg and predicted progression (p < 0.0001). In 120 untreated RA patients, the risk-score for predicting treatment-induced remission using naïve T-cells had an odds ratio of 15.4 (p < 0.0001). In RA patients in treatment-induced remission, a score using naïve T-cells predicted disease flare (p < 0.0001). Evaluating the risk of progression using naïve CD4+ T-cells was predictive of progression along the whole IA-continuum. This should allow identification of individuals at high-risk of progression, permitting targeted therapy for improved outcomes.

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Section: Quantification Of T-cell Subsetsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Patients Materials and Methodsmentioning

confidence: 99%

Section: Quantification Of T-cell Subsetsmentioning

confidence: 97%

See 2 more Smart Citations

T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

Ponchel

Burska

Hunt

et al. 2020

Sci Rep

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“…If aiming for a state closer to normality (true remission), a concept of multi-dimensional remission (MDR) should be used, involving the achievement of different depths of remission, using clinical, imaging and additional serological, immunological or histological parameters [33]. MDR has been shown to be related to better patient-reported outcomes, although prospective data is necessary to de nitely address this issue.…”

Section: Discussionmentioning

confidence: 99%

Comparable Clinical and Radiographic Outcomes among DAS28-ESR-based Remission Criteria and SDAI, CDAI, and ACR/EULAR Boolean definitions in patients with Established Rheumatoid Arthritis in Clinical Practice. Observational Study of 5 years of Follow-Up

Ramírez¹,

Inciarte-Mundo²,

Cuervo³

et al. 2020

Preprint

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Objective To compare long-term clinical and radiographic outcomes among five sets of remission criteria [four clinical and one Ultrasound (US)-based] in a cohort of RA patients in a clinical care setting. Methods RA patients in remission (DAS28-ESR <2.6) were selected. Hand US assessments were performed, and serum levels of inflammation/angiogenesis biomarkers were determined at baseline. Changes in baseline treatment and radiographic progression, defined as the variation in the modified Sharp van der Heijde score (mSHS) at 5 years, were analyzed. To define remission, five different concepts were used, as follows: DAS28-ESR<2.6, SDAI<3.3, CDAI<2.8, Boolean criteria and score Power Doppler (PD)=0.Results Eighty-seven patients with DAS28-ESR<2.6 were included. One third fulfilled SDAI (33.3%), CDAI (31%) and Boolean (35.6%) remission criteria and 25.3% had no PD signal in the US evaluation. 26 patients (29.9%) changed the therapy, ranging from 13.6% (PD remission) to 33.3% (CDAI remission) (p=0.11). Serum levels of ANG (p=0.015) and TNFa (p=0.025) were significantly lower in patients with Boolean remission, whereas IL-18 levels were significantly lower in those with PD remission (p=0.049). Patients without PD in the US assessment had significantly lower mSHS erosion progression (p=0.014) at 5 years. Conclusions Patients with established RA in DAS28-ESR remission had comparable clinical and radiographic outcomes than SDAI, CDAI and Boolean definitions in a clinical care setting. US remission remained as the closest to structural damage abrogation.

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Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy

Gul,

Di Matteo,

Anioke

et al. 2024

ACR Open Rheumatology

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ObjectiveThe tapering of biologic disease‐modifying antirheumatic drug (b‐DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b‐DMARD–induced clinical remission, who did or did not follow structured b‐DMARD tapering.MethodsPatients with RA receiving b‐DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) <2.6 for ≥6 months were offered tapering. Clinical, ultrasound (US) (total power Doppler [PD]/grayscale abnormalities), CD4+ T cell subsets, and patient‐reported outcomes (PROs) were collected at inclusion. The primary endpoint was the occurrence of flare (loss of DAS28‐CRP remission) over 12 months. Logistic regression analyses identified predictors of flare. Dichotomization into high/low‐risk groups was based on 80% specificity using the area under the receiving operator curve (AUROC).ResultsOf 63 patients choosing tapering, 23 (37%) flared compared with 12 of 60 (20%) on stable treatment (P = 0.043). All patients who flared regained remission upon reinstating treatment. In the tapering group, flare was associated with lower regulatory T cell (Treg) (P < 0.0001) and higher CRP levels (P < 0.0001), erythrocyte sedimentation rate (P < 0.035), and inflammation‐related cells (IRCs) (P = 0.054); stepwise modeling selected Tregs (odds ratio [OR] = 0.350, P = 0.004), IRCs (OR = 1.871, P = 0.007), and CRP level (OR = 1.577, P = 0.004) with 81.7% accuracy and AUROC = 0.890. In the continued therapy group, modeling retained the tender joint count, total PD, and visual analog scale pain score, with 82.1% accuracy and AUROC = 0.899. Most patients in the study were considered low risk of flare (80 of 123 patients [65%]). Only 5 of 37 (13.5%) of the low‐risk patients who tapered flared, which was notable compared with the continued therapy group (20% flare).ConclusionFlare on tapering b‐DMARDs was predicted by lower Tregs and elevated inflammation biomarkers (IRCs/CRP level); flare on continued b‐DMARDs was associated with raised pain parameters and US inflammation. Knowledge of these biomarkers should improve outcomes by targeted selection for tapering, and by increased monitoring of those on continued therapy predicted to flare.

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Defining remission in rheumatoid arthritis: does it matter to the patient? A comparison of multi-dimensional remission criteria and patient reported outcomes

Cited by 20 publications

References 32 publications

T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

T-cell subset abnormalities predict progression along the Inflammatory Arthritis disease continuum: implications for management

Comparable Clinical and Radiographic Outcomes among DAS28-ESR-based Remission Criteria and SDAI, CDAI, and ACR/EULAR Boolean definitions in patients with Established Rheumatoid Arthritis in Clinical Practice. Observational Study of 5 years of Follow-Up

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy

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