Dit proefschrift richt zich op het symptomatische voorstadium van reumatoïde artritis, clinically suspect arthalgia, met de volgende doelstellingen: beter begrijpen van de symptomen en de hieraan... Show moreDit proefschrift richt zich op het symptomatische voorstadium van reumatoïde artritis, clinically suspect arthalgia, met de volgende doelstellingen: beter begrijpen van de symptomen en de hieraan onderliggende mechanismen (deel I), met MRI in de CSA-fase meerleren over het ontstaan van RA en identificeren van mensen met een verhoogd risico op RA (deel II), onderzoeken of medicamenteuze behandeling in de CSA-fase zin heeft en hoe deze behandeling eruit zou moeten zien (deel III). Show less
Webers, C.; Kiltz, U.; Braun, J.; Heijde, D. van der; Boonen, A. 2022
Objective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational... Show moreObjective To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. Methods Data from the observational Assessment of SpondyloArthritis international Society Health Index Validation Study were used. Patients were assessed at baseline and after initiation of NSAIDs/conventional synthetic DMARDs (csDMARDs)/TNF inhibitors (TNFis). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale depression subscale [HADS-D; 0-21 (best-worst)]. Covariables included demographics and disease characteristics, including disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)/BASDAI]. The change in HADS-D from baseline was compared between treatments (NSAIDs/csDMARDs/TNFis) with analysis of variance and multivariable regression analysis. Results A total of 304 patients were included; 102/45/157 initiated NSAIDs/csDMARDs/TNFis and 260 (85%) / 44 (15%) had axial/peripheral SpA. At baseline, the mean HADS-D was 6.9 (s.d. 4.2); 126 (42%) were possibly depressed (HADS-D >= 8) and 66 (22%) were probably depressed (HADS-D >= 11). At follow-up, depressive symptoms significantly improved in all treatment groups. In multivariable regression without disease activity measures, initiating TNFis compared with NSAIDs was associated with greater improvement in depressive symptoms [beta = -1.27 (95% CI -2.23, -0.32)] and lower odds of possible depression at follow-up [odds ratio 0.47 (95% CI 0.23, 0.94)]. This association was attenuated after additional adjustment for disease activity (ASDAS/BASDAI) but not CRP. csDMARDs did not differ from NSAIDs regarding their effect on HADS-D. Between-drug class results were confirmed in axial SpA (axSpA), although less clear in peripheral SpA. Conclusion Treatment of active SpA also improves depressive symptoms. Especially in axSpA, TNFis have a greater effect than NSAIDs, which is mainly explained by a stronger effect on disease activity. We found no evidence for a direct link between CRP-mediated inflammation and depressive symptoms in SpA. Show less
Background Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight... Show moreBackground Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months. Methods Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression. Results Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI. Conclusion We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated. Show less
Background Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight... Show moreBackground Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months. Methods Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression. Results Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI. Conclusion We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated. Show less
Objectives: To assess the discontinuation of first-line biological treatment and to evaluate the reasons and predictors thereof in patients with rheumatoid arthritis (RA) from daily clinical... Show moreObjectives: To assess the discontinuation of first-line biological treatment and to evaluate the reasons and predictors thereof in patients with rheumatoid arthritis (RA) from daily clinical practice.Methods: RA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) starting treatment with biologic DMARDs (bDMARDs) were included in this prospective observational study. The main outcome was the time to discontinuation (in years) due to any cause. Discontinuation was defined as a 90-day discontinuation of treatment or the occurrence of any switch to another bDMARD during follow-up. Baseline and time-varying sociodemographic and clinical characteristics were tested as possible predictors of discontinuation using multivariable Cox models.Results: Of the 1,851 RA patients included in the study, 871 (47%) discontinued their first bDMARD. The median overall persistence of the first bDMARD was 5.5 years and the leading cause of discontinuation was inefficacy [N=476 (55%)], followed by adverse events [N=262 (30%)], other causes [N=69, (8%)] and unknown causes [N=64 (7%)]. Patients with a higher HAQ score (more disability) at baseline were more likely to discontinue their first bDMARD [hazard ratio (HR):1.39 (95% CI: 1.17-1.64)], as were patients with a higher number of comorbidities [HR: 1.17 (1.05-1.29)] and patients starting treatment from 2007 onwards [HR:1.89 (1.5-2.38)]. On the contrary, receiving TNFi bDMARD [HR:0.74 (0.57-0.94)] as opposed to non-TNFi was associated with less discontinuation. Expectedly, the higher the DAS28 during follow-up the higher the likelihood to discontinue bDMARD [HR:1.08 (1.06-1.1)]. No other time-varying predictor was found.Conclusion: In the Portuguese RA population, maintenance of first-line bDMARD was shown to be relatively high. Inefficacy was the leading cause of discontinuation. Features found to predict drug discontinuation (e.g. baseline disability) may contribute to inform clinician's decisions in clinical practice. Show less
The Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED)-study is a multicentre two-step randomized single-blinded clinical trial in 610 early... Show moreThe Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED)-study is a multicentre two-step randomized single-blinded clinical trial in 610 early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) patients. Intensive induction therapy (methotrexate (MTX) and a tapered high dose of prednisone) was started in the first 4 months. Treatment adjustments aimed at clinical remission (Disease Activity Score (DAS)<1.6): if DAS<1.6, medication was tapered and stopped, if DAS≥1.6, medication was intensified or restarted. Patients not in DAS-remission after 4 months were randomized to triple therapy (MTX, hydroxychloroquine and sulfasalazine) with prednisone (arm 1) or MTX+adalimumab (arm 2).After 4 months 61% was in DAS-remission (early DAS-remission group). After 5 years, 48% were in DAS-remission and 22% in drug-free remission (DFR). Patients in early DAS-remission group had better functional ability and more often achieved DAS-remission and DFR than patients that were randomized, without differences between the arms. UA patients had lower DAS and less autoantibody positivity at baseline compared to the RA patients. DAS-remission percentages were comparable between RA and UA patients, but more UA patients did achieve DFR (33% vs 19%). Autoantibody (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)) negative patients more often achieved DFR. Show less
