scholarly journals Baseline predictors of remission, pain and fatigue in rheumatoid arthritis: the TITRATE trial

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Sook Yan Lee ◽  
Fowzia Ibrahim ◽  
Brian D. M. Tom ◽  
Elena Nikiphorou ◽  
Frances M. K. Williams ◽  
...  

Abstract Background Clinical trials show intensive treatment to induce remission is effective in patients with highly active rheumatoid arthritis (RA). The TITRATE trial showed that the benefits of intensive treatment also extend to moderately active RA. However, many patients failed to achieve remission or show improvements in pain and fatigue. We investigated whether baseline predictors could identify treatment non-responders. Methods The impact of obesity, depression, anxiety and illness perception on RA outcomes, including disease activity, remission, pain and fatigue were determined using a pre-planned secondary analysis of the TITRATE trial data. Results Body mass index was associated with disease activity levels and remission: obese patients had a higher overall disease activity and fewer obese patients achieved remission. Intensive management was not associated with increased remission in these patients. Obesity was also associated with increased overall pain and fatigue. Anxiety, depression and health perceptions had no discernible impact on disease activity but were associated with high levels of pain and fatigue. There was a strong association between anxiety and high pain scores; and between depression and high fatigue scores; and health perception was strongly related to both. None of the predictors had an important impact on pain and fatigue reduction in cross-sectional analysis. Conclusions Disease activity is higher in obese patients and they have fewer remissions over 12 months. Anxiety, depression and health perceptions were associated with higher pain and fatigue scores. Intensive management strategies need to account for these baseline features as they impact significantly on clinical and psychological outcomes. Trial registration ISRCTN 70160382; date registered 16 January 2014

2021 ◽  
Author(s):  
Sook Yan Lee ◽  
Fowzia Ibrahim ◽  
Brian Tom ◽  
Elena Nikiphorou ◽  
Frances Williams ◽  
...  

Abstract Background Clinical trials show intensive treatment to induce remission is effective in patients with highly active rheumatoid arthritis (RA). The TITRATE trial showed that the benefits of intensive treatment also extend to moderately active RA. However, many patients failed to achieve remission or show improvements in pain and fatigue. We investigated whether baseline predictors could identify treatment non-responders. Methods The impact of obesity, depression, anxiety and illness perception on RA outcomes, including disease activity, remission, pain and fatigue were determined using a pre-planned secondary analysis of the TITRATE trial data. Results Body mass index was associated with disease activity levels and remission: obese patients had a higher overall disease activity and fewer obese patients achieved remission. Intensive management was not associated with increased remission in these patients. Obesity was also associated with increased overall pain and fatigue. Anxiety, depression and health perceptions had no discernible impact on disease activity but were associated with high levels of pain and fatigue. There was a strong association between anxiety and high pain scores; and between depression and high fatigue scores; and health perception was strongly related to both. None of the predictors had an important impact on pain and fatigue reduction in cross-sectional analysis. Conclusions Disease activity is higher in obese patients and they have fewer remissions over 12 months. Anxiety, depression and health perceptions were associated with higher pain and fatigue scores. Intensive management strategies need to account for these baseline features as they impact significantly on clinical and psychological outcomes.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 900.1-900
Author(s):  
L. Diebold ◽  
T. Wirth ◽  
V. Pradel ◽  
N. Balandraud ◽  
E. Fockens ◽  
...  

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 478.2-479
Author(s):  
L. Zhang ◽  
C. van der Tog ◽  
A. den Broeder ◽  
T. Mellors ◽  
E. Connolly-Strong ◽  
...  

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Gorica G. Ristić ◽  
Vesna Subota ◽  
Dejana Stanisavljević ◽  
Danilo Vojvodić ◽  
Arsen D. Ristić ◽  
...  

Abstract Objective To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.


2019 ◽  
Vol 11 (5) ◽  
pp. 216-223
Author(s):  
Mohamed Baraka ◽  
Hossam ElDessouky ◽  
Alaa Abdel Azeez Labeeb ◽  
Eman Ezzat ◽  
Asmaa ElDessouky

Background: Rheumatoid arthritis (RA) is an autoimmune systemic disease with a wide clinical presentation. The laryngeal manifestations are often masked by the articular disability often experienced in the early and late stages of the disease. Objective: Association between different laryngeal complaints and videolaryngoscopic laryngeal alterations in patients with RA, and disease activity and duration. Patients and methods: A retrospective study was conducted on 79 patients with RA. All subjects were recruited from the out-patient clinic of physical medicine, rehabilitation, and rheumatology in Al-Menoufia University Hospitals during the period from March 2015 to March 2017. All patients were subjected to both phoniatric and rheumatological assessment. Results: Patients with phonasthenic symptoms and globus pharynges had significantly (p=0.01, 0.008 respectively) higher disease duration than patients without. No significant association found between rheumatoid arthritis duration and different videolaryngoscopic laryngeal alterations, patient’s self-assessment of the impact of laryngeal complaints on their lives, and auditory perceptual assessment (APA) of patient’s voice characters. As regards rheumatoid disease's activity no significant correlation has been established (p>0.05) with different laryngeal complaints except for patients in remission who had higher prevalence of intermittent dysphonia than patients with low activities. Rheumatoid disease's activity had no significant association with different laryngeal findings except those with moderate activity; they had significantly higher prevalence of vocal folds nodules than patients with high activity and patients in remission. Conclusion: A significant association between the disease's duration and presence of laryngeal complaints, dysphonia, and its persistence has been established. Also, patients with phonasthenic symptoms and globus pharynges had significantly higher disease duration than patients without. Rheumatoid diseases activity had significant association with different laryngeal complaints in patients with remission that had higher prevalence of intermittent dysphonia than patients with low activities. No significant association between the disease activity and different laryngeal findings that has been found except for patients with DAS-28>3.2, they had significantly higher prevalence of rheumatoid nodules.


2020 ◽  
pp. annrheumdis-2020-218419
Author(s):  
Viktor Molander ◽  
Hannah Bower ◽  
Thomas Frisell ◽  
Johan Askling

ObjectiveTo assess the incidence of venous thromboembolism (VTE) in rheumatoid arthritis (RA) relative to individuals without RA, and to investigate the relationship between aspects of clinical disease activity in RA and the risk of VTE.MethodsWe conducted a nationwide register-based cohort study 2006 through 2018 using the Swedish Rheumatology Quality Register linked to other national patient registers to identify all patients with RA with at least one registered rheumatologist visit during the study period (n=46 316 patients, 322 601 visits). The Disease Activity Score 28 erythrocyte sedimentation rate (ESR) (DAS28 ESR) and its components served as the exposure, and a VTE event within the year following the visit was the main outcome. We also included general population referents (1:5) matched on age, sex and residential area.ResultsBased on 2241 incident VTE events within 1 year of each included visit, and 5301 VTE events in the general population cohort, the risk ratio for VTE in RA was 1.88 (95% CI 1.65 to 2.15). Among patients with RA, the risk (and risk ratio) increased with increasing RA disease activity, from 0.52% following visits in remission to 1.08% following visits with DAS28 ESR high disease activity, RR compared with remission=2.03, 95% CI 1.73 to 2.38. Compared with the general population, also patients with RA in DAS28 ESR remission were at elevated VTE risk.ConclusionsThis study demonstrates a strong association between clinical RA disease activity measured by DAS28 ESR and the risk of VTE. RA disease activity can be used as an additional tool for VTE risk stratification in patients with RA.


Author(s):  
Chris Deighton

Influential guidelines on rheumatoid arthritis (RA) management agree on most key recommendations. Early diagnosis of persistent synovitis, and identification of poor prognostic markers, is essential. Rapid intervention is vital with drugs to suppress inflammation, slow down damaging disease components, and prevent disability. The label of RA covers a broad spectrum of disease severity, and there is controversy on: • whether the same interventions are needed for all patients • whether monotherapy or combination treatment is appropriate • the role of steroids in RA • the appropriate introduction of biological therapies. Treating to specified targets is optimal evidence-based practice, where patients are reviewed regularly for disease activity assessments, and inadequate control rectified. Aiming for remission is the ultimate goal, though for some patients minimal disease activity may be appropriate. Patient education addressing self-management is important, and the multidisciplinary team (MDT: specialist nurses, physiotherapists, occupational therapists, podiatrists, psychologists) needs to be involved from the start to minimize the impact on quality of life of the patient. For established disease, rapid access is important for flares, and to consider whether disease management could be improved. An intermittent overview of established disease is important with access to the MDT, and assessments for comorbidities such as ischaemic heart disease, osteoporosis, and depression, as well as complications of the disease itself such as cervical spine disease, vasculitis, and lung and eye complications. An informed patient needs to be central to all decision making.


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