BackgroundPrevious studies have shown that using a finger prick as the primary method for blood w... more BackgroundPrevious studies have shown that using a finger prick as the primary method for blood withdrawal is an efficient way to collect blood samples remotely, and data on blood levels from a finger prick are directly comparable to that obtained by a venepuncture. During the COVID-19 pandemic, we therefore complemented our large digital research platform with serum collection via a home finger prick testing in order to collect samples without the need of visits to a hospital. This repeatedly enabled us to rapidly answer new and relevant clinical research questions about COVID-19, thereby showing the potential of the finger prick for research purposes. However, the use of finger pricks in a research or clinical practice setting is still uncommon, and not yet tested on a large scale. In addition, there is limited data on peoples’ willingness and ability to successfully use the finger prick at home, especially in patients with inflammatory rheumatic diseases (iRD) who may have impair...
Background:Although an increased risk of inflammatory bowel disease (IBD) during etanercept (ETN)... more Background:Although an increased risk of inflammatory bowel disease (IBD) during etanercept (ETN) use is included in the product information of ETN, no other gastro-intestinal (GI-)adverse drug reactions (ADRs) are described. This is in contrast with other TNFα-inhibitors such as adalimumab (ADA) and infliximab, as these are associated with various GI-ADRs such as nausea and abdominal pain.Objectives:To identify the proportion and type of patient-reported and health care professional (HCP)-reported ETN associated GI-ADRs and compare these with ADA associated GI-ADRs.Methods:Patient-reported data on ADRs attributed to biologics was collected from the Dutch Biologic Monitor (DBM) from 1 Jan 2017 until 1 Nov 2019. HCP reported data on ADRs attributed to biologics was collected from the Dutch rheumatic arthritis monitoring registry and the Dutch registry for spondyloarthritis from 22 Jun 2004 until 1 Nov 2019.GI-ADRs were defined by MedDRA System Organ Class ‘Gastrointestinal disorders’...
BackgroundConcerns have been raised regarding risks of COVID-19 breakthrough infections in vaccin... more BackgroundConcerns have been raised regarding risks of COVID-19 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases (IMIDs) treated with immunosuppressants, but data on COVID-19 breakthrough infections in these patients are still scarce.ObjectivesThe primary objective was to compare the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 delta variant between fully vaccinated IMID patients with immunosuppressants, and controls (IMID patients without immunosuppressants and healthy controls). The secondary objective was to explore determinants of breakthrough infections.MethodsIn this study we pooled data collected from two large ongoing prospective multi-center cohort studies (Target to-B! [T2B!] study and ARC study). Clinical data were collected between February and December 2021, using digital questionnaires, standardized electronic case record forms and medical files. Post-vaccination serum samples were analyzed for ...
BackgroundImmunogenicity of adalimumab (ADL) has been the subject of extensive research, with the... more BackgroundImmunogenicity of adalimumab (ADL) has been the subject of extensive research, with the primary focus on its incidence, antibody titers and effects on clinical outcome. However, the temporal evolution of antibodies, i.e. dynamic and variation in titers, time point of emergent and persistence or transience of the response, remains under elucidated. To investigate this further, it is essential to collect samples at regular intervals and over a longer period of time. Also, a drug tolerant assay should be used to conquer with the phenomenon of drug interference (1).ObjectivesTo evaluate the temporal evolution and to distinguish dynamic patterns of antibody response. Secondly, to assess the clinical impact and factors influencing these dynamic patterns.MethodsADA and adalimumab concentration were measured in sera of 511 consecutive ADL treated rheumatoid arthritis patients. Serum samples were drawn at week 0, 4, 16, 28, 52, 78 and 104. ADA were measured with a drug tolerant ass...
Background:The majority of patients with a rheumatic disease treated with etanercept may be overe... more Background:The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering is scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Dose reductions can potentially reduce blood drug levels too much, resulting in loss of effect.Objectives:We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study.Methods:160 consecutive patients with rheumatoid arthritis (RA), PsA or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomised controlled trial. The intervention group doubled the dosing-interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose up to 6 months, after which the dosing-interval was doubled. Primary outcome was the proportion of patients maintaining ...
OBJECTIVE Several biomarkers of cardiovascular function are found to be increased in rheumatoid a... more OBJECTIVE Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.
Background:Accelerated atherosclerosis is a systemic manifestation of rheumatoid arthritis (RA). ... more Background:Accelerated atherosclerosis is a systemic manifestation of rheumatoid arthritis (RA). E-selectin, VCAM-1, MCP1/CCL2 and IL-8/CXCL8 are involved in leukocyte migration through endothelial cells in both atherosclerosis and RA [1]. Therefore, these endothelial function markers might reflect endothelial function and systemic inflammation in RA. If so, such a marker could be used to assess cardiovascular risk in RA patients.Objectives:The aim of this study was to investigate the effect of 6 months of anti-inflammatory treatment on RA serum levels of endothelial function markers and whether these serum levels are related to prognostic imaging markers for atherosclerosis.Methods:E-selectin, VCAM-1, MCP1 and IL-8 serum levels were determined at baseline and after 6 months of therapy with MTX monotherapy or in combination with adalimumab for 40 RA patients and 19 osteoarthritis (OA) controls using commercial ELISA kits. Prognostic imaging markers for atherosclerosis were pulse wav...
Background:Apremilast is an oral phosphodiesterase 4 inhibitor and approved drug for treatment of... more Background:Apremilast is an oral phosphodiesterase 4 inhibitor and approved drug for treatment of Psoriatic Arthritis(PsA). Previous studies show apremilast to be efficacious and safe. (1) However, physician are sometimes reluctant to prescribe apremilast in clinical practice due to its perceived side effects, and relatively small effect size (1).Objectives:In this study we investigated the occurrence and frequencies of adverse events, and the effects of patient expectation management on drug survival for PsA patient starting apremilast.Methods:From March 2017 to December 2019, 21 consecutive patients have been included in the apremilast PsA cohort at Reade in Amsterdam, the Netherlands. The initial high dropout rate that was observed with usual care led to a revision in the baseline visit with more emphasis placed on patient expectation management.Results:From the usual care group (UCG; n=12), 10 patients (83%) stopped apremilast within the first year: 6 (50%) due to adverse events...
Background:Persons at high risk for developing rheumatoid arthritis (RA) may benefit from a low-r... more Background:Persons at high risk for developing rheumatoid arthritis (RA) may benefit from a low-risk pharmacological intervention aimed at primary prevention. Statins are safe and widely-used drugs; previous studies demonstrated disease-modifying effects of statins in RA patients1as well as an association between statin use and a decreased risk of RA development2.Objectives:We designed a multi-center, randomized, double-blind, placebo-controlled trial to investigate if atorvastatin use for 3 years could prevent arthritis.Methods:Persons at high risk for RA, defined by the presence of arthralgia and anti-citrullinated protein antibody (ACPA) concentration >3xULN or both ACPA and rheumatoid factor (RF), were randomized to atorvastatin 40 mg daily or placebo for 3 years. Eligible participants were ≥18 years, had no indication for lipid-lowering therapy and had no clinical synovitis. The primary endpoint was development of clinical arthritis. Our goal was to include 220 patients, bas...
Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthrit... more Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthritis (RA) signs and symptoms in phase (P)3 trials.1–3 RA elevates cardiovascular disease risk; statins are used to reduce risk.Objectives:To assess safety of statin and filgotinib coadministration across the clinical program.Methods:Patients (pts) meeting 2010 ACR/EULAR RA criteria in P2 DARWIN 1–2 (D1–2; NCT01888874, NCT01894516), P3 FINCH 1–3 (F1–3; NCT02889796, NCT02873936, NCT02886728), and long-term extensions DARWIN 3 and FINCH 4 (D3, F4; NCT02065700, NCT03025308) receiving FIL 100 mg (FIL100) QD, FIL 200 mg QD (FIL200), adalimumab (ADA), methotrexate (MTX), or placebo (PBO) were included. Events related to statin use were analysed as exposed by treatment received. N and % were provided.Week (W)12 PBO-controlled safety analysis included pts receiving FIL100, FIL200, or PBO for ≤12W (D1–2, F1–2); as-treated safety analysis included pts receiving long-term FIL100 QD (n=1647), FIL200 QD...
595 (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 month... more 595 (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 months (T6) of treatment. RF titers and serum drug levels were measured at T0 and T6 using nephelometry and ELISA respectively. Association between baseline RF titers and drug levels was assessed using non-parametric test (Mann-Whitney). Results: 168 patients were evaluated: 90 received IFX, 48 ADA and 32 CZP. Characteristics at T0 are shown in Table 1. All patients had active disease at baseline and 76% were RF positive: ADA subgroup had lower percentage of positive RF than IFX and CZP subgroups. Patients were stratified into quartiles based on baseline RF titers: low (20-57 IU/ml), medium (57-380 IU/ml), high (>380 IU/ml) and seronegative (<20 IU/ml). Drug levels of IFX and ADA at T6 were significantly lower in those patients who had higher RF titers at T0 compared to seronegative. In contrast, CZP levels remained stable irrespectively of baseline RF titers, without significant differences among quartiles (Figure 1). Conclusion: Higher baseline RF titers are associated with lower IFX and ADA levels at T6 in a cohort of RA patients. A concentration-response association has been clearly established for TNFi, and baseline RF levels appear to influence drug levels. Reduced immune complexes formation with CZP may result in a limited impact of baseline RF titers on drug levels.
BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease... more BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. This risk is similar to that of diabetes mellitus (DM). There have been no studies comparing the coronary microvascular dysfunction assessed with coronary flow reserve (CFR) of RA patients to both patients with DM and a control group (=patients without RA, without DM and no cardiovascular event).ObjectivesTo assess the difference in coronary microvascular dysfunction in patients with RA in comparison to patients with DM and control group.MethodsFrom our 13NH3 myocardial PET/CT registry we included all patients that were included from December 2013 until March 2019. A total of 33 patients with RA, 299 patients with DM and 179 control patients (=patients without RA and without DM) were analyzed. Myocardial blood flow was quantified at rest and under stress induced by administrating adenosine. Coronary flow reserve was calculated by dividing MBF under stress by MBF in rest. CFR < 2 was...
BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of etanercept ... more BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of etanercept in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering the burden of the ADRs. However, not every ADR causes the same burden for patients. Information is lacking about the degree of experienced burden per ADR by patients with IRDs.ObjectivesFirst, to describe ADRs of etanercept based on nature, frequency and burden, and second, to propose a new model for identification of relevant ADRs for health care professionals.MethodsData of the Dutch Biologic Monitor (DBM) was used to categorize patient-reported ADRs into high and low burden. In this prospective cohort event monitoring system patients were asked to fill out bimonthly questionnaires on experienced ADRs that they attributed to the use of a biological DMARD. The questionnaire included a quantification of the burden of the reported ADRs using a five-point Likert s...
Background: EULAR recommends biologic initiation in combination with MTX in RA patients after fai... more Background: EULAR recommends biologic initiation in combination with MTX in RA patients after failure of conventional synthetic (cs)DMARDs and in the presence of poor prognostic factors. Low-dose glucocorticoids should also be considered, but should be tapered as rapidly as is clinically feasible.1 [for full text, please go to the a.m. URL]
Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature.... more Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alte...
BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of adalimumab ... more BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of adalimumab in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering the burden of the ADRs. However, not every ADR causes the same burden for patients. Information is lacking about the degree of experienced burden per ADR by patients with IRDs.ObjectivesFirst, to describe ADRs of adalimumab based on nature, frequency and burden, and second to propose a new model for identification of relevant ADRs for health care professionals.MethodsData of the Dutch Biologic Monitor (DBM) was used to categorize patient-reported ADRs into high and low burden. In this prospective cohort event monitoring system patients were asked to fill out bimonthly questionnaires on experienced ADRs that they attributed to the use of a biological. The questionnaire included a quantification of the burden of the reported ADRs using a five-point Likert scale ra...
BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembol... more BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients.ObjectivesTo assess the effects of different initial treatments on hemostatic parameters in patients with early RA.MethodsNORD-STAR is an international, multicentre, open-label, assessor-blinded, phase 4 study where patients with newly diagnosed RA started methotrexate (MTX) and were randomised 1:1:1:1 to a) conventional treatment (either prednisolone tapered to 5mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab1. This study is a spin-off from the main NORD-STAR study extensively investigating hemostatic system in 24 per protocol consecutive Dutch participants at baseline, 12 weeks and 24 weeks after the start of the treatment. Statistical analy...
BackgroundCurrently, patients with rheumatoid arthritis (RA) require frequent consultations to mo... more BackgroundCurrently, patients with rheumatoid arthritis (RA) require frequent consultations to monitor their disease activity. However, since a majority of patients is in remission during routine follow up, it should be possible to reduce the number of consultations for them.1 Patients that are meeting their treatment goal, based on the results of their electronic patient reported outcome measures (ePROMs), could be eligible to skip their visit. Research revealed that patients who indicate to be in remission or have a low disease activity (remission/LDA) on their ePROMs, such as the routine assessment of patient index data (RAPID3), also have a low disease activity score 28 (DAS28).2 However, in clinical practice the decision to intensify treatment is more complex than not meeting a DAS28 threshold. Therefore, ePROM-results should be compared with treatment intensifications to assess the safety of screening with ePROMs.ObjectivesTo assess the probability that patients with low score...
Treatment response and remission rates were assessed based on the changes in disease activity sco... more Treatment response and remission rates were assessed based on the changes in disease activity scores. Data analyses were performed according to disease type (UC/CD), and further stratified by treatment history (biologic-naïve/failure patients). Treatment persistence was assessed using Kaplan-Meier analysis. Adverse events (AEs) recorded in patients' files were collected. Results: Of the 418 patients who started VDZ (safety population), 325 (202 CD and 123 UC) eligible patients were included in data analyses (effectiveness population). 22.2% of UC and 34.2% of CD patients were biologic-naïve. About three-quarters of the patients achieved clinical response at W10/W14 (CD: 71.4%; UC: 77.2%) that persisted up to M6 (CD: 75.6%; UC: 83.9%). At M6, 66.7% of CD patients were in remission; the response and remission rates were numerically higher among biologic-naïve patients (UC, respectively, additional 9% and 24%; CD, additional 22% and 35.8%) (Table 2) .At M6, 87.6% of CD and 86.1% of UC patients were still on VDZ treatment. For 7.7% of patients, VDZ dose was escalated to every 4W. The most common AEs (n = 418) were arthralgia (3.8%), fatigue (3.6%), skin eruption (3.1%), headache (2.9%) and gastroenteritis (2.6%). Conclusions: After 6 months of treatment with VDZ, about 85% of patients were still on treatment, of whom more than 40% achieved remission. Treatment effectiveness appeared higher in biologic-naïve compared with biologic-failure patients. No new safety signals were raised. These results are consistent with findings from the Phase III and real-world evidence studies with VDZ.
BackgroundPrevious studies have shown that using a finger prick as the primary method for blood w... more BackgroundPrevious studies have shown that using a finger prick as the primary method for blood withdrawal is an efficient way to collect blood samples remotely, and data on blood levels from a finger prick are directly comparable to that obtained by a venepuncture. During the COVID-19 pandemic, we therefore complemented our large digital research platform with serum collection via a home finger prick testing in order to collect samples without the need of visits to a hospital. This repeatedly enabled us to rapidly answer new and relevant clinical research questions about COVID-19, thereby showing the potential of the finger prick for research purposes. However, the use of finger pricks in a research or clinical practice setting is still uncommon, and not yet tested on a large scale. In addition, there is limited data on peoples’ willingness and ability to successfully use the finger prick at home, especially in patients with inflammatory rheumatic diseases (iRD) who may have impair...
Background:Although an increased risk of inflammatory bowel disease (IBD) during etanercept (ETN)... more Background:Although an increased risk of inflammatory bowel disease (IBD) during etanercept (ETN) use is included in the product information of ETN, no other gastro-intestinal (GI-)adverse drug reactions (ADRs) are described. This is in contrast with other TNFα-inhibitors such as adalimumab (ADA) and infliximab, as these are associated with various GI-ADRs such as nausea and abdominal pain.Objectives:To identify the proportion and type of patient-reported and health care professional (HCP)-reported ETN associated GI-ADRs and compare these with ADA associated GI-ADRs.Methods:Patient-reported data on ADRs attributed to biologics was collected from the Dutch Biologic Monitor (DBM) from 1 Jan 2017 until 1 Nov 2019. HCP reported data on ADRs attributed to biologics was collected from the Dutch rheumatic arthritis monitoring registry and the Dutch registry for spondyloarthritis from 22 Jun 2004 until 1 Nov 2019.GI-ADRs were defined by MedDRA System Organ Class ‘Gastrointestinal disorders’...
BackgroundConcerns have been raised regarding risks of COVID-19 breakthrough infections in vaccin... more BackgroundConcerns have been raised regarding risks of COVID-19 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases (IMIDs) treated with immunosuppressants, but data on COVID-19 breakthrough infections in these patients are still scarce.ObjectivesThe primary objective was to compare the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 delta variant between fully vaccinated IMID patients with immunosuppressants, and controls (IMID patients without immunosuppressants and healthy controls). The secondary objective was to explore determinants of breakthrough infections.MethodsIn this study we pooled data collected from two large ongoing prospective multi-center cohort studies (Target to-B! [T2B!] study and ARC study). Clinical data were collected between February and December 2021, using digital questionnaires, standardized electronic case record forms and medical files. Post-vaccination serum samples were analyzed for ...
BackgroundImmunogenicity of adalimumab (ADL) has been the subject of extensive research, with the... more BackgroundImmunogenicity of adalimumab (ADL) has been the subject of extensive research, with the primary focus on its incidence, antibody titers and effects on clinical outcome. However, the temporal evolution of antibodies, i.e. dynamic and variation in titers, time point of emergent and persistence or transience of the response, remains under elucidated. To investigate this further, it is essential to collect samples at regular intervals and over a longer period of time. Also, a drug tolerant assay should be used to conquer with the phenomenon of drug interference (1).ObjectivesTo evaluate the temporal evolution and to distinguish dynamic patterns of antibody response. Secondly, to assess the clinical impact and factors influencing these dynamic patterns.MethodsADA and adalimumab concentration were measured in sera of 511 consecutive ADL treated rheumatoid arthritis patients. Serum samples were drawn at week 0, 4, 16, 28, 52, 78 and 104. ADA were measured with a drug tolerant ass...
Background:The majority of patients with a rheumatic disease treated with etanercept may be overe... more Background:The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering is scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Dose reductions can potentially reduce blood drug levels too much, resulting in loss of effect.Objectives:We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study.Methods:160 consecutive patients with rheumatoid arthritis (RA), PsA or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomised controlled trial. The intervention group doubled the dosing-interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose up to 6 months, after which the dosing-interval was doubled. Primary outcome was the proportion of patients maintaining ...
OBJECTIVE Several biomarkers of cardiovascular function are found to be increased in rheumatoid a... more OBJECTIVE Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.
Background:Accelerated atherosclerosis is a systemic manifestation of rheumatoid arthritis (RA). ... more Background:Accelerated atherosclerosis is a systemic manifestation of rheumatoid arthritis (RA). E-selectin, VCAM-1, MCP1/CCL2 and IL-8/CXCL8 are involved in leukocyte migration through endothelial cells in both atherosclerosis and RA [1]. Therefore, these endothelial function markers might reflect endothelial function and systemic inflammation in RA. If so, such a marker could be used to assess cardiovascular risk in RA patients.Objectives:The aim of this study was to investigate the effect of 6 months of anti-inflammatory treatment on RA serum levels of endothelial function markers and whether these serum levels are related to prognostic imaging markers for atherosclerosis.Methods:E-selectin, VCAM-1, MCP1 and IL-8 serum levels were determined at baseline and after 6 months of therapy with MTX monotherapy or in combination with adalimumab for 40 RA patients and 19 osteoarthritis (OA) controls using commercial ELISA kits. Prognostic imaging markers for atherosclerosis were pulse wav...
Background:Apremilast is an oral phosphodiesterase 4 inhibitor and approved drug for treatment of... more Background:Apremilast is an oral phosphodiesterase 4 inhibitor and approved drug for treatment of Psoriatic Arthritis(PsA). Previous studies show apremilast to be efficacious and safe. (1) However, physician are sometimes reluctant to prescribe apremilast in clinical practice due to its perceived side effects, and relatively small effect size (1).Objectives:In this study we investigated the occurrence and frequencies of adverse events, and the effects of patient expectation management on drug survival for PsA patient starting apremilast.Methods:From March 2017 to December 2019, 21 consecutive patients have been included in the apremilast PsA cohort at Reade in Amsterdam, the Netherlands. The initial high dropout rate that was observed with usual care led to a revision in the baseline visit with more emphasis placed on patient expectation management.Results:From the usual care group (UCG; n=12), 10 patients (83%) stopped apremilast within the first year: 6 (50%) due to adverse events...
Background:Persons at high risk for developing rheumatoid arthritis (RA) may benefit from a low-r... more Background:Persons at high risk for developing rheumatoid arthritis (RA) may benefit from a low-risk pharmacological intervention aimed at primary prevention. Statins are safe and widely-used drugs; previous studies demonstrated disease-modifying effects of statins in RA patients1as well as an association between statin use and a decreased risk of RA development2.Objectives:We designed a multi-center, randomized, double-blind, placebo-controlled trial to investigate if atorvastatin use for 3 years could prevent arthritis.Methods:Persons at high risk for RA, defined by the presence of arthralgia and anti-citrullinated protein antibody (ACPA) concentration >3xULN or both ACPA and rheumatoid factor (RF), were randomized to atorvastatin 40 mg daily or placebo for 3 years. Eligible participants were ≥18 years, had no indication for lipid-lowering therapy and had no clinical synovitis. The primary endpoint was development of clinical arthritis. Our goal was to include 220 patients, bas...
Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthrit... more Background:The Janus kinase-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthritis (RA) signs and symptoms in phase (P)3 trials.1–3 RA elevates cardiovascular disease risk; statins are used to reduce risk.Objectives:To assess safety of statin and filgotinib coadministration across the clinical program.Methods:Patients (pts) meeting 2010 ACR/EULAR RA criteria in P2 DARWIN 1–2 (D1–2; NCT01888874, NCT01894516), P3 FINCH 1–3 (F1–3; NCT02889796, NCT02873936, NCT02886728), and long-term extensions DARWIN 3 and FINCH 4 (D3, F4; NCT02065700, NCT03025308) receiving FIL 100 mg (FIL100) QD, FIL 200 mg QD (FIL200), adalimumab (ADA), methotrexate (MTX), or placebo (PBO) were included. Events related to statin use were analysed as exposed by treatment received. N and % were provided.Week (W)12 PBO-controlled safety analysis included pts receiving FIL100, FIL200, or PBO for ≤12W (D1–2, F1–2); as-treated safety analysis included pts receiving long-term FIL100 QD (n=1647), FIL200 QD...
595 (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 month... more 595 (ADA) or CZP. Clinical and demographic data were collected at baseline (T0) and after 6 months (T6) of treatment. RF titers and serum drug levels were measured at T0 and T6 using nephelometry and ELISA respectively. Association between baseline RF titers and drug levels was assessed using non-parametric test (Mann-Whitney). Results: 168 patients were evaluated: 90 received IFX, 48 ADA and 32 CZP. Characteristics at T0 are shown in Table 1. All patients had active disease at baseline and 76% were RF positive: ADA subgroup had lower percentage of positive RF than IFX and CZP subgroups. Patients were stratified into quartiles based on baseline RF titers: low (20-57 IU/ml), medium (57-380 IU/ml), high (>380 IU/ml) and seronegative (<20 IU/ml). Drug levels of IFX and ADA at T6 were significantly lower in those patients who had higher RF titers at T0 compared to seronegative. In contrast, CZP levels remained stable irrespectively of baseline RF titers, without significant differences among quartiles (Figure 1). Conclusion: Higher baseline RF titers are associated with lower IFX and ADA levels at T6 in a cohort of RA patients. A concentration-response association has been clearly established for TNFi, and baseline RF levels appear to influence drug levels. Reduced immune complexes formation with CZP may result in a limited impact of baseline RF titers on drug levels.
BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease... more BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. This risk is similar to that of diabetes mellitus (DM). There have been no studies comparing the coronary microvascular dysfunction assessed with coronary flow reserve (CFR) of RA patients to both patients with DM and a control group (=patients without RA, without DM and no cardiovascular event).ObjectivesTo assess the difference in coronary microvascular dysfunction in patients with RA in comparison to patients with DM and control group.MethodsFrom our 13NH3 myocardial PET/CT registry we included all patients that were included from December 2013 until March 2019. A total of 33 patients with RA, 299 patients with DM and 179 control patients (=patients without RA and without DM) were analyzed. Myocardial blood flow was quantified at rest and under stress induced by administrating adenosine. Coronary flow reserve was calculated by dividing MBF under stress by MBF in rest. CFR < 2 was...
BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of etanercept ... more BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of etanercept in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering the burden of the ADRs. However, not every ADR causes the same burden for patients. Information is lacking about the degree of experienced burden per ADR by patients with IRDs.ObjectivesFirst, to describe ADRs of etanercept based on nature, frequency and burden, and second, to propose a new model for identification of relevant ADRs for health care professionals.MethodsData of the Dutch Biologic Monitor (DBM) was used to categorize patient-reported ADRs into high and low burden. In this prospective cohort event monitoring system patients were asked to fill out bimonthly questionnaires on experienced ADRs that they attributed to the use of a biological DMARD. The questionnaire included a quantification of the burden of the reported ADRs using a five-point Likert s...
Background: EULAR recommends biologic initiation in combination with MTX in RA patients after fai... more Background: EULAR recommends biologic initiation in combination with MTX in RA patients after failure of conventional synthetic (cs)DMARDs and in the presence of poor prognostic factors. Low-dose glucocorticoids should also be considered, but should be tapered as rapidly as is clinically feasible.1 [for full text, please go to the a.m. URL]
Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature.... more Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alte...
BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of adalimumab ... more BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of adalimumab in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering the burden of the ADRs. However, not every ADR causes the same burden for patients. Information is lacking about the degree of experienced burden per ADR by patients with IRDs.ObjectivesFirst, to describe ADRs of adalimumab based on nature, frequency and burden, and second to propose a new model for identification of relevant ADRs for health care professionals.MethodsData of the Dutch Biologic Monitor (DBM) was used to categorize patient-reported ADRs into high and low burden. In this prospective cohort event monitoring system patients were asked to fill out bimonthly questionnaires on experienced ADRs that they attributed to the use of a biological. The questionnaire included a quantification of the burden of the reported ADRs using a five-point Likert scale ra...
BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembol... more BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients.ObjectivesTo assess the effects of different initial treatments on hemostatic parameters in patients with early RA.MethodsNORD-STAR is an international, multicentre, open-label, assessor-blinded, phase 4 study where patients with newly diagnosed RA started methotrexate (MTX) and were randomised 1:1:1:1 to a) conventional treatment (either prednisolone tapered to 5mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab1. This study is a spin-off from the main NORD-STAR study extensively investigating hemostatic system in 24 per protocol consecutive Dutch participants at baseline, 12 weeks and 24 weeks after the start of the treatment. Statistical analy...
BackgroundCurrently, patients with rheumatoid arthritis (RA) require frequent consultations to mo... more BackgroundCurrently, patients with rheumatoid arthritis (RA) require frequent consultations to monitor their disease activity. However, since a majority of patients is in remission during routine follow up, it should be possible to reduce the number of consultations for them.1 Patients that are meeting their treatment goal, based on the results of their electronic patient reported outcome measures (ePROMs), could be eligible to skip their visit. Research revealed that patients who indicate to be in remission or have a low disease activity (remission/LDA) on their ePROMs, such as the routine assessment of patient index data (RAPID3), also have a low disease activity score 28 (DAS28).2 However, in clinical practice the decision to intensify treatment is more complex than not meeting a DAS28 threshold. Therefore, ePROM-results should be compared with treatment intensifications to assess the safety of screening with ePROMs.ObjectivesTo assess the probability that patients with low score...
Treatment response and remission rates were assessed based on the changes in disease activity sco... more Treatment response and remission rates were assessed based on the changes in disease activity scores. Data analyses were performed according to disease type (UC/CD), and further stratified by treatment history (biologic-naïve/failure patients). Treatment persistence was assessed using Kaplan-Meier analysis. Adverse events (AEs) recorded in patients' files were collected. Results: Of the 418 patients who started VDZ (safety population), 325 (202 CD and 123 UC) eligible patients were included in data analyses (effectiveness population). 22.2% of UC and 34.2% of CD patients were biologic-naïve. About three-quarters of the patients achieved clinical response at W10/W14 (CD: 71.4%; UC: 77.2%) that persisted up to M6 (CD: 75.6%; UC: 83.9%). At M6, 66.7% of CD patients were in remission; the response and remission rates were numerically higher among biologic-naïve patients (UC, respectively, additional 9% and 24%; CD, additional 22% and 35.8%) (Table 2) .At M6, 87.6% of CD and 86.1% of UC patients were still on VDZ treatment. For 7.7% of patients, VDZ dose was escalated to every 4W. The most common AEs (n = 418) were arthralgia (3.8%), fatigue (3.6%), skin eruption (3.1%), headache (2.9%) and gastroenteritis (2.6%). Conclusions: After 6 months of treatment with VDZ, about 85% of patients were still on treatment, of whom more than 40% achieved remission. Treatment effectiveness appeared higher in biologic-naïve compared with biologic-failure patients. No new safety signals were raised. These results are consistent with findings from the Phase III and real-world evidence studies with VDZ.
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Papers by M. Nurmohamed