35 research outputs found
Outcome measures in Sjögren's disease
Full text linkIn this thesis, ‘Outcome measures in Sjögren’s disease’, we researched outcome measures which are used to measure treatment effect in clinical trials in Sjögren’s disease. Sjögren’s disease is a systemic autoimmune disease, which means that the immune system attacks cells of its own body. In Sjögren’s disease this leads to inflammation of tear and salivary glands. The disease is characterized by dryness complaints of eyes and mouth, fatigue and arthralgia or tendinomyalgia. However, every organ can be affected, leading to a very heterogeneous clinical picture. Currently, no effective systemic treatment is available for patients with Sjögren’s disease, despite the fact that many clinical trials have been performed in past years. These clinical trials were not able to show efficacy of the treatment compared to placebo. In this thesis, we analysed commonly used outcome measures in Sjögren’s disease, such as measures for systemic disease activity (activity in various organs) and patient-reported symptoms, and we researched the application of these outcome measures in various types of research, both clinical trials as observational cohort studies. Because Sjögren’s disease is very heterogeneous, with many different symptoms which can differ per patient, we developed a composite endpoint to measure treatment effect in clinical trials, the Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS). The CRESS combines several different outcome measures. With the CRESS, we were able to show efficacy of the treatment compared to placebo, while previously, these trials were not able to show treatment effect. We believe these findings are an important step in finding effective treatment for patients with Sjögren’s disease
TROUGH SERUM DRUG LEVELS AND DISEASE ACTIVITY IN AXIAL SPONDYLOARTHRITIS PATIENTS ON LONG-TERM TREATMENT WITH TNF-A INHIBITORS
No full textChange in disease activity is associated with TNF-alpha inhibitor serum levels in patients with axial spondyloarthritis in daily clinical practice
Full text linkObjectiveTo investigate, in daily clinical practice, TNF-alpha inhibitor serum trough levels in patients experiencing an increase in axial spondyloarthritis (ax-SpA) related symptoms. Secondly, to explore if these serum trough levels are associated with disease activity (DA) and/or change in DA.MethodsPatients from the GLAS cohort treated with TNF-alpha inhibitors who had a serum trough level measurement during follow-up because of an increase in ax-SpA related symptoms between June 2015 and June 2018 were included. Serum trough levels were stratified in a therapeutic and below therapeutic range, based on published reference values of Sanquin in 2019. DA was assessed by ASDAS and BASDAI and change in DA (i.e. AASDAS or BASDAI compared to the visit before increasing symptoms).Results31 patients had a serum trough level measurement because of increasing symptoms. These patients had a median treatment duration of 4.8 years (IQR 0.9-8.6). 22 (71%) had active disease according to ASDAS (score >= 2.1) and 15 (47%) had therapeutic drug levels. The increase in DA was significantly larger in patients with below therapeutic drug levels compared to patients with therapeutic levels (AASDAS: 0.94 +/- 0.81 vs. -0.07 +/- 126, pConclusionIn this observational study in daily clinical practice, approximately half of ax-SpA patients who experienced an increase in symptoms had below therapeutic TNF-alpha inhibitor serum trough levels. Change in DA and not absolute DA scores was significantly associated with drug levels.</p
Ten years of the ESSDAI:is it fit for purpose?
Full text linkPrimary Sjögren's syndrome (pSS) is a very heterogeneous disease with systemic manifestations such as arthritis, skin, lung and renal involvement. To be able to assess systemic disease activity, the EULAR Sjögren's syndrome disease activity index (ESSDAI) was developed for use in daily clinical practice and in clinical trials. Since its development it has been widely used in cohort studies and clinical trials. The ESSDAI gives a systematic overview of a patient's systemic disease activity, which is very useful in daily clinical practice. However, using the ESSDAI as outcome measure in trials has been more challenging. Several RCTs with the ESSDAI as primary endpoint failed and showed large 'response rates' in placebo-treated patients as well. In this review, we discuss what we learned from using the ESSDAI in cohorts and clinical trials. We recommend to use the ESSDAI only in combination with other important outcome measures, such as patient-reported symptoms and glandular function as part of a composite endpoint in clinical trials in pSS patients.</p
Minimal added value of separate dryness assessments compared with overall dryness in ESSPRI in patients with Sjögren’s disease
Full text linkHigh BMI is associated with lower TNF-α inhibitor serum trough levels and higher disease activity in patients with axial spondyloarthritis
Full text linkBACKGROUND: TNF-α inhibitor (TNFi) serum trough levels have previously been found to be related to disease activity in axial spondyloarthritis (axSpA). However, most research regarding serum trough levels has been conducted in patients who only recently started TNFi therapy. Therefore, our objective was to explore TNFi serum trough level measurements in relation to disease activity and BMI in the total axSpA population in daily clinical practice, also including patients on long-term TNFi therapy.METHODS: Consecutive patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were approached for a TNFi serum trough level measurement during their regular outpatient visit at the UMCG. Spearman's correlation coefficient was used to analyse the relation of serum trough levels with disease activity and BMI. Logistic regression was performed to analyse the relation between therapeutic drug levels and disease activity, corrected for potential confounders, including BMI.RESULTS: Thirty-four patients on adalimumab and 21 patients on etanercept were included. Mean age was 45 ± 12 years, 47% were male, median BMI was 26.4 (IQR 23.9-32.5) and median treatment duration was 41 months (range 2-126). According to definitions of Sanquin, 47% of patients had therapeutic serum trough levels. No significant correlations were found between TNFi levels and disease activity (ASDAS-CRP: adalimumab: ρ = -0.16, p = 0.39; etanercept: ρ = -0.29, p = 0.20). TNFi levels were moderately correlated with BMI (adalimumab: ρ = -0.48, p = 0.004; etanercept: ρ = -0.50, p = 0.021). Patients with active disease (ASDAS ≥ 2.1) showed higher BMI than patients with inactive disease (median 29.7 vs. 24.6, p = 0.015). In multivariable regression analyses, BMI was identified as the only confounder for the relationship between therapeutic drug levels and ASDAS.CONCLUSION: In this cross-sectional, observational study of axSpA patients mainly on long-term treatment with TNFi, higher BMI was significantly associated with lower adalimumab and etanercept serum trough levels and higher disease activity.</p
Performance of the Clinical Trials ESSDAI (ClinTrialsESSDAI), an Adjusted ESSDAI Score, in Two Randomised Clinical Trials in Patients with Primary Sjogren's Syndrome
No full textBackground/Purpose: Recent randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to show clinical efficacy.1-3 Several RCTs used the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) as primary endpoint, showing large response rates in active treatment and placebo groups.1,3 The ESSDAI consists of some domains which are more sensitive to change and easy to score compared to other domains.4 The objective of this study was to develop the Clinical Trials ESSDAI (ClinTrialsESSDAI), an adjusted ESSDAI score consisting of frequently active and sensitive to change domains, and to compare the performance of the ClinTrialsESSDAI to the Clinical (Clin)ESSDAI and ESSDAI in two RCTs.Methods: The ASAP-III trial in abatacept (80 pSS patients)1 and TRACTISS trial in rituximab (133 pSS patients)2 were used for development and analyses of the ClinTrialsESSDAI. These trials were selected since ASAP-III included only patients with moderate to high disease activity according to ESSDAI, whereas TRACTISS did not apply this inclusion criterion, leading to higher baseline ESSDAI scores in ASAP-III than in TRACTISS (median 13 vs. 4). Activity of ESSDAI domains at baseline was analysed. The six most frequently active domains were selected for the ClinTrialsESSDAI, with exclusion of the biological domain. This is in line with the ClinESSDAI, which does not include the biological domain, to measure a ‘true’ clinical effect. The ClinTrialsESSDAI score was calculated using existing weights of the ClinESSDAI. Responsiveness of the ClinTrialsESSDAI, ClinESSDAI and ESSDAI was calculated using the standardised response mean (SRM) at the primary endpoint visits: week 24 for ASAP-III, week 48 for TRACTISS. Percentage of patients who reached the minimal clinically important improvement (MCII, decrease of ≥3 points) and low disease activity (LDA, score < 5) was analysed for all three scores.Results: Besides the biological domain, the six most frequently active domains at baseline in the ASAP-III and TRACTISS trial were the glandular (any activity: 91% and 21%, respectively), articular (58% and 44%), haematological (43% and 24%), constitutional (46% and 15%), lymphadenopathy (29% and 9%) and cutaneous (23% and 11%) domain (Figure 1). These domains were selected for the ClinTrialsESSDAI. Responsiveness was similar using any of the three scores at primary endpoint visits of the ASAP-III and TRACTISS trials (Table 1). Discrimination between active treatment and placebo groups based on MCII and LDA responders was also similar using any of the three scores (Figure 2).Conclusion: The ClinTrialsESSDAI, consisting of six frequently active and sensitive to change domains of the ESSDAI, shows similar responsiveness and discrimination between treatment groups compared to the ClinESSDAI and ESSDAI in the ASAP-III and TRACTISS RCT. Therefore, this ClinTrialsESSDAI will not solve the problem of discrimination and a composite endpoint combining response at multiple clinically relevant items seems more suitable as primary study endpoint
Additional file 1 of High BMI is associated with lower TNF-α inhibitor serum trough levels and higher disease activity in patients with axial spondyloarthritis
No full textAdditional file 1: Supplementary Table 1. Baseline characteristics of 55 axSpA patients with a random adalimumab or etanercept serum trough level measurement compared to 36 patients on adalimumab or etanercept without measurement
Ten years of the ESSDAI:is it fit for purpose?
Full text linkPrimary Sjögren's syndrome (pSS) is a very heterogeneous disease with systemic manifestations such as arthritis, skin, lung and renal involvement. To be able to assess systemic disease activity, the EULAR Sjögren's syndrome disease activity index (ESSDAI) was developed for use in daily clinical practice and in clinical trials. Since its development it has been widely used in cohort studies and clinical trials. The ESSDAI gives a systematic overview of a patient's systemic disease activity, which is very useful in daily clinical practice. However, using the ESSDAI as outcome measure in trials has been more challenging. Several RCTs with the ESSDAI as primary endpoint failed and showed large 'response rates' in placebo-treated patients as well. In this review, we discuss what we learned from using the ESSDAI in cohorts and clinical trials. We recommend to use the ESSDAI only in combination with other important outcome measures, such as patient-reported symptoms and glandular function as part of a composite endpoint in clinical trials in pSS patients.</p
