Defining the Optimal Strategies for Achieving Drug-Free Remission in Rheumatoid Arthritis: A Narrative Review

Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; however, it is recommended that patients can taper therapy, with a view to discontinuing and achieving drug-free remission if treatment goals are maintained. This narrative review aims to present the current literature on drug-free remission in rheumatoid arthritis, with a view to identifying which strategies are best for disease-modifying anti-rheumatic drug (DMARD) tapering and to highlight areas of unmet clinical need. Methods: We performed a narrative review of the literature, which included research articles, meta-analyses and review papers. The key search terms included were rheumatoid arthritis, remission, drug-free remission, b-DMARDS/biologics, cs-DMARDS and tapering. The databases that were searched included PubMed and Google Scholar. For each article, the reference section of the paper was reviewed to find additional relevant articles. Results: It has been demonstrated that DFR is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. Conclusions: DFR in RA may be an achievable goal in certain patients. This carries importance in reducing medication-induced side-effects and potential toxicity, the burden of taking treatment if not required and cost effectiveness, specifically for biologic therapy. Prospective studies of objective biomarkers will help facilitate the prediction of successful treatment discontinuation.

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Fatigue is cross-sectionally not associated with objective assessments of inflammation, but changes in fatigue are associated with changes of disease activity assessments during biologic treatment of patients with established rheumatoid arthritis

Clinical Rheumatology ◽

10.1007/s10067-020-05402-y ◽

2020 ◽

Author(s):

Hilde Berner Hammer ◽

Brigitte Michelsen ◽

Joe Sexton ◽

Till Uhlig ◽

Sella A. Provan

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Outcome Measures ◽

Power Doppler ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Patient Reported ◽

Remission Rates ◽

Global Disease Activity

Abstract Objective The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients the cross-sectional and longitudinal relation of fatigue with subjective as well as objective assessments of disease activity. Methods RA patients were consecutively included when initiating biologic disease-modifying anti-rheumatic drugs (DMARDs) and assessed at baseline, 1, 2, 3, 6, and 12 months with investigation of fatigue, patient-reported outcome measures (PROMs; joint pain and patient’s global disease activity, MHAQ, pain catastrophizing, Mental Health score), clinical examinations (examiner’s global disease activity, 28 tender and swollen joint counts), and laboratory variables (ESR, CRP, calprotectin). Ultrasound examinations (semi-quantitative scoring (0–3)) with grey scale and power Doppler were performed of 36 joints and 4 tendons. Statistics included one-way analysis of variance, Pearson’s correlations, and multiple linear and logistic regression analysis. Results A total of 208 RA patients (mean (SD) age 53.2 (13.2) years, disease duration 9.8 (8.5) years) were included. Fatigue levels diminished during follow-up (mean (SD) baseline/12 months; 4.8 (2.8)/3.0 (2.5) (p < 0.001)). Substantial correlations were cross-sectionally found between fatigue and PROMs (median (IQR) r=0.61 (0.52-0.71)) but not with the objective inflammatory assessments. During follow-up, baseline fatigue was associated with PROMs (p < 0.001) but not with objective inflammatory assessments. However, change of fatigue was associated with change in all variables. Higher baseline fatigue levels were associated with lower clinical composite score remission rates. Conclusion Fatigue was cross-sectionally associated to subjective but not to objective disease assessments. However, change of fatigue during treatment was associated to all assessments of disease activity. Trial registration number Anzctr.org.au identifier ACTRN12610000284066, Norwegian Regional Committee for Medical and Health Research Ethics South East reference number 2009/1254 Key Points• In this longitudinal study of patients with established RA, fatigue was associated with patient reported outcome measures at each visit, but not with objective assessments of inflammation including calprotectin and comprehensive ultrasound examinations.• Changes in fatigue during biological treatment were associated with changes in patient reported outcome measures, clinical, laboratory and ultrasound assessments.• Baseline fatigue was associated with all patient reported outcome measures, but not objective assessments of inflammation at all the prospective visits.• Higher baseline fatigue levels were associated with lower remission rates as assessed by clinical composite scores.

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FRI0020 CLINICAL TREATMENT RESPONSE STILL DOES NOT MATCH PATIENT REPORTED IMPROVEMENT, EVEN IN EARLY RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2116 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 582.1-582

Author(s):

S. Pazmino ◽

A. Lovik ◽

A. Boonen ◽

D. De Cock ◽

V. Stouten ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Early Rheumatoid Arthritis ◽

Health Assessment ◽

Sustained Remission ◽

Research Support ◽

Early Ra ◽

Severity Scores ◽

Patient Reported ◽

Over Time

Background:Commonly used disease activity scores in rheumatoid arthritis (RA) include one patient reported outcome (PRO) -the patient’s global health assessment (PGA). Exploratory factor analysis (EFA) was performed on data from the 2 year Care in early Rheumatoid Arthritis (CareRA) trial to explain the evolution of disease burden extracting 3 factors.1Objectives:To assess the evolution and relative responsiveness over time of clinical, laboratory and patient assessments included in composite scores, together with other PROs like pain, fatigue and functionality in patients with early RA (≤1 year) treated to target (T2T) within the CareRA trial.Methods:DMARD naïve patients with early RA (n=379) were included, randomized to remission induction with COBRA-like treatment schemes (n=332) or MTX monotherapy (n=47) and T2T.Components of disease activity scores (swollen/tender joint count (S/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), and physician (PhGH) or patient (PGA) global health assessment), pain and fatigue (both on 0-100 scale) and HAQ were recorded at every visit.Missing data was handled with multiple imputation (n=15). Clustering was removed with multiple outputation (n=1000), then each of the 15 000 datasets was analyzed by EFA with principal component extraction and oblimin rotation. The analyses were combined after re-ordering the factors by maximizing factor congruence. The 3 extracted factors and their individual components (with their loadings) were: 1. Patient containing PGA (0.87), pain (0.86), fatigue (0.90) and HAQ (0.5) 2.Clinical with SJC (0.92), TJC (0.89) and PhGH (0.76) and 3.Laboratory with CRP(0.87) and ESR (0.78).1(Pazmino, ACR 2019 abstract, Table 3)Afterwards, variables were first normalized to a 0-1 scale, then multiplied -weighted- by the factor loadings previously obtained.1For each Patient, Clinical and Laboratory severity score, the weighted variables belonging to each score were summed together and then re-scaled to 0-1 (higher values suggest more burden).The percentage (%) improvement from baseline to week 104 and the area under the curve (AUC) across time points were calculated per factor.Differences in % improvement and AUC were compared between patients not achieving and achieving early and sustained (week 16 to 104) disease activity score remission (DAS28CRP <2.6) with ANOVA. Bonferroni correction was used for multiple testing.Results:Severity scores of Patient, Clinical and Laboratory factors improved rapidly over time (Figure 1). In patients achieving sustained remission (n=122), Patient, Clinical and Laboratory scores improved 56%, 90% and 27% respectively. In patients not achieving sustained remission (n=257) the improvement was 32%, 78% and 9% respectively (p<0.001 only for clinical improvement).Patients in CareRA who achieved sustained remission had an AUC of 15.1, 3.4 and 4.7 in Patient, Clinical and Laboratory scores respectively, compared to 32.3, 10.0, and 7.2 in participants not achieving sustained remission (p<0.001 for all comparisons).Conclusion:Patient, Clinical and Laboratory severity scores improved rapidly over time in patients achieving rapid and sustained disease control. However, overall, Patient burden seemed not to improve to the same extent as Clinical burden. Patient’s unmet needs in terms of pain, fatigue, functionality and overall well-being should thus be given more attention, even in patients in sustained remission.References:[1]Pazmino S,et al.Including Pain, Fatigue and Functionality Regularly in the Assessment of Patients with Early Rheumatoid Arthritis Separately Adds to the Evaluation of Disease Status [abstract]. ACR. 2019.Disclosure of Interests:Sofia Pazmino: None declared, Anikó Lovik: None declared, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department), Diederik De Cock: None declared, Veerle Stouten: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

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AB1304 THE RHEUMATOID ARTHRITIS FLARE QUESTIONNAIRE (RA-FQ) IS AN EASY TO ADMINISTER PATIENT-REPORTED OUTCOME MEASURE THAT TRACKS WELL WITH THE CLINICAL DISEASE ACTIVITY INDEX (CDAI) OVER TIME IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS (ERA) IN 2 DIFFERENT HEALTH SETTINGS

10.1136/annrheumdis-2019-eular.4977 ◽

2019 ◽

Author(s):

Vivian Bykerk ◽

Orit Schieir ◽

Marie-France Valois ◽

Glen Hazlewood ◽

Gilles Boire ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Early Rheumatoid Arthritis ◽

Outcome Measure ◽

Activity Index ◽

Disease Activity Index ◽

Patient Reported Outcome ◽

Patient Reported Outcome Measure ◽

Patient Reported ◽

Over Time

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Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.141480 ◽

2016 ◽

Vol 43 (4) ◽

pp. 699-706 ◽

Cited By ~ 13

Author(s):

Tuomas Rannio ◽

Juha Asikainen ◽

Arto Kokko ◽

Pekka Hannonen ◽

Tuulikki Sokka

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Joint Disease ◽

Treat To Target ◽

Sustained Remission ◽

Duration Of Symptoms ◽

Erosive Disease ◽

Rheumatology Clinic ◽

Patient Reported ◽

Remission Rates

Objective.We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA).Methods.Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care.Results.Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4–12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36).Conclusion.Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.

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Clinical Ankle Involvement and Ultrasound Synovial Hypertrophy are Significant Predictors of DAS28-Defined Rheumatoid Arthritis Disease Activity

Internal Medicine ◽

10.2478/inmed-2019-0057 ◽

2019 ◽

Vol 16 (2) ◽

pp. 19-33

Author(s):

Luminiţa Enache ◽

Claudiu C. Popescu ◽

Cătălin Codreanu ◽

Maria Șuţa

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Ankle Joint ◽

Clinical Examination ◽

Power Doppler ◽

Independent Effect ◽

Joint Involvement ◽

Synovial Hypertrophy ◽

Rheumatoid Arthritis Disease ◽

Patient Reported

AbstractObjective. The study aimed to investigate the relationship between ankle involvement and disease activity in rheumatoid arthritis (RA), from clinical and ultrasound perspectives.Methods. RA patients were recruited in 2018 in the random order of presentation from the out-patient clinic. On the same day of inclusion, all patients underwent clinical examination, laboratory tests (inflammatory markers), ankle ultrasound and patient-reported outcomes.Results. The study included 183 patients with established RA, mostly women (86.3%), with mean age of 57.3 years. Clinical examination revealed 101 (55.2%) patients with at least one tender ankle and 56 (30.6%) patients with at least one swollen ankle. Regression analysis revealed that both clinically tender and swollen ankles were 2.8 and respectively 3.4 times more likely to reveal ultrasound ankle joint synovial hypertrophy (SH). The presence of ankle SH was associated with higher disease activity: for example, compared to patients without ankle SH, patients with ultrasound-detected SH in any ankle joint had significantly higher median DAS28CRP (4.60 compared to 2.73, p<0.001). Power Doppler (PD) activity of ankle SH produced similar results: PD signal presence (p<0.001) and PD grade (p = 0.009) were associated with higher median DAS28CRP. Ankle joint involvement had an independent effect on DAS28CRP-defined disease activity: for example, the absence of ankle SH independently and significantly decreased DAS28CRP with 0.985 points (p<0.001).Conclusion. Clinical ankle involvement and ultrasound-detected ankle SH have a directly proportional relationship with disease activity in RA.

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Cotreatment with methotrexate in routine care patients with rheumatoid arthritis receiving biological treatment yields better outcomes over time

RMD Open ◽

10.1136/rmdopen-2018-000836 ◽

2019 ◽

Vol 5 (1) ◽

pp. e000836 ◽

Cited By ~ 3

Author(s):

Niels W. Boone ◽

Alexandre Sepriano ◽

Paul-Hugo van der Kuy ◽

Rob Janknegt ◽

Ralph Peeters ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Combination Therapy ◽

Disease Activity ◽

Estimating Equation ◽

Routine Care ◽

Patient Reported Outcome ◽

Joint Disease ◽

Continuous Variables ◽

Patient Reported ◽

Over Time

ObjectivesWe aimed to evaluate the effects of methotrexate (MTX) comedication added to biological disease-modifying antirheumatic drugs (bDMARD) on disease activity measures in patients with rheumatoid arthritis (RA) in routine care.MethodsPatients with RA on treatment with either bDMARDs or conventional synthetic DMARDs were included in this prospective cohort study. The effect of (time-varying) combination therapy with bDMARD and MTX compared with bDMARD monotherapy was tested in longitudinal generalised estimating equation models using as outcomes: (1) the likelihood to be in remission according to the 28-joint Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) (<2.6) and to the Routine Assessment of Patient Index Data 3 (RAPID3) (0–30; ≤3), a patient-reported outcome measure about RA symptoms; and (2) DAS28-ESR and RAPID3 as continuous variables. All models were adjusted for potential confounders: age, gender, drugs for comorbidities (yes/no), oral steroids (yes/no) and non-steroidal anti-inflammatory drug (yes/no).ResultsIn total, 330 patients were included (mean (SD) follow-up; 10.7 (9.7) months). Compared with bDMARD monotherapy, MTX combination therapy was significantly associated with a 55% higher likelihood to be in DAS28 remission, but not RAPID3 remission, over time. Combination therapy resulted in slightly, but statistically significant, lower levels of DAS28-ESR over time (β=−0.42 (95% CI −0.67 to − 0.17)), but not RAPID3 (β=−0.58 (95% CI −0.65 to 0.49)). The effect on DAS28-ESR was entirely explained by lower swollen joint counts and was persistent after correction for confounders.ConclusionThese results give support to the policy that MTX should be continued in routine care patients with RA on biological therapy since this leads to better objective but not subjective clinical outcomes

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Toward Electronic Health Recording: Evaluation of Electronic Patient-reported Outcome Measures System for Remote Monitoring of Early Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.151421 ◽

2016 ◽

Vol 43 (12) ◽

pp. 2106-2112 ◽

Cited By ~ 21

Author(s):

Yasser El Miedany ◽

Maha El Gaafary ◽

Sally Youssef ◽

Sami Bahlas ◽

Samah Almedany ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Early Rheumatoid Arthritis ◽

Patient Reported Outcome Measures ◽

Patient Reported Outcome ◽

Control Group ◽

Patient Reported ◽

Standard Paper ◽

Group 2 ◽

Group 1

Objective.To assess the use of electronic patient-reported outcome measures (ePROM) in standard clinical practice for early rheumatoid arthritis (RA) management, the ePROM ability to enhance clinical care, and how computing technology can improve the patients’ adherence to therapy.Methods.In a double-blinded randomized-controlled study, 211 patients with early RA diagnosed according to American College of Rheumatology/European League Against Rheumatism criteria completed a PROM in paper format at their first clinic visit. Patients were then randomized to Group 1, which completed an ePROM questionnaire monthly, or Group 2, which continued the standard paper PROM format. Over a 12-month period, Group 1 patients were assessed every 3 months in the clinic, whereas Group 2 patients were assessed in the clinic initially monthly for 6 months, then every 3 months. The primary endpoint was the equivalence of outcomes [Routine Assessment of Patient Index Data 3 (RAPID-3) and 28-joint Disease Activity Score (DAS28)] in both groups. The secondary endpoint was the patients’ adherence to their medications.Results.There was no significant difference between disease activity measures as well as DAS28 and RAPID-3 scores at 3, 6, and 12 months of management, although there was a trend toward lower patient-reported tender joint count and functional disability score in the active group versus the control group. The patients’ adherence to antirheumatic therapy was significantly higher (p < 0.01) in the ePROM group, whereas stopping disease-modifying antirheumatic drugs for intolerability was significantly higher (p < 0.01) in the control group at 12 months of treatment.Conclusion.We found ePROM equivalent to standard paper PROM format. Further, it enabled the patients to personally monitor how they are doing regarding their disease activity and helped to optimize their adherence to their treatment.

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