Eveline van der Veer

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

IntroductionIdentifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.MethodsAS outpatients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-α treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively.ResultsBetween November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patients global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-α blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level.ConclusionsBesides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-α blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-α treatment.

Vitamin D status and outcomes in heart failure patients

Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin–angiotensin system (RAS) and inflammatory markers could explain this potential association.

High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis.

Indolent systemic mastocytosis (ISM) is a rare disease characterized by accumulation of abnormal mast cells in various tissues, including bone marrow. Symptoms are usually related to release of mast cell mediators. The aims are to establish the prevalence of osteoporotic fractures in ISM and to investigate the association with serum tryptase and the urinary histamine metabolites, methylhistamine (MH), and methylimidazole acetic acid.

Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis

BACKGROUND Increased basal serum tryptase (bsT) levels are a well-described risk factor for Hymenoptera venom-induced anaphylaxis (HVAn) in patients allergic to Hymenoptera venom. Increased bsT levels might also indicate the presence of mastocytosis. In this study we evaluated whether the risk of HVAn increases with increasing mast cell load in patients with mastocytosis. METHODS Consecutive patients with different subtypes of mastocytosis (n = 329) admitted to the University Medical Center Groningen were retrospectively assessed. As markers for mast cell load, levels of both bsT and the urinary histamine metabolites methylhistamine and methylimidazole acetic acid (MIMA) were used. RESULTS In the entire patient group, irrespective of disease subtype and Hymenoptera venom exposure, HVAn prevalence gradually increased with increasing marker levels to a maximum of 36% to 47% at a bsT level of 28.0 μg/L, a methylhistamine level of 231.0 μmol/mol creatinine, and a MIMA level of 2.7 mmol/mol creatinine but decreased thereafter with a further increase in these levels. In patients with indolent systemic mastocytosis with a history of Hymenoptera venom exposure after age 15 years or greater (n = 152), MIMA and age at the most recent Hymenoptera sting were independent predictors for HVAn (odds ratios of 0.723 [P = .001] and 1.062 [P < .001], respectively). CONCLUSIONS In patients with mastocytosis, HVAn prevalence does not increase constantly with increasing levels of mast cell load parameters: after a gradual increase to a maximum of near 50%, it decreases with a further increase in these levels. In the indolent systemic mastocytosis population, all mast cell load markers were independent negative predictors of HVAn. These findings suggest a complex pathophysiologic association between mast cell load and HVAn risk in patients with mastocytosis.

Prevalence of indolent systemic mastocytosis in a Dutch region

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Appetite suppression through smelling of dark chocolate correlates with changes in ghrelin in young women

Cephalic effects on appetite are mediated by vagal tone and altered gastrointestinal hormones. The objective of this study is to explore the relationship between appetite and levels of gastrointestinal hormones after smelling chocolate and after melt-and-swallow 30 g chocolate (1.059 oz, 85% cocoa, 12.5 g of sugar per 100g product). Twelve female residents (BMI between 18 and 25 kg/m(2)) all participated in two 60-minute study sessions. In the first session, all 12 women ate chocolate; for the second session, they were randomized either to smell chocolate (n=6) or to serve as a control (no eating or smelling; n=6). At the start of the sessions, levels of insulin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), but not glucose, correlated with appetite scored on a visual analogue scale (VAS). In contrast, ghrelin levels correlated inversely with scored appetite. Chocolate eating and smelling both induced a similar appetite suppression with a disappearance of correlations between VAS scores and insulin, GLP-1 and CCK levels. However, while the correlation between VAS score and ghrelin disappeared completely after chocolate eating, it reversed after chocolate smelling, that is, olfactory stimulation with dark chocolate (85%) resulted in a satiation response that correlated inversely with ghrelin levels.

Myopathy during statin therapy in the daily practice of an outpatient cardiology clinic: prevalence, predictors and relation with vitamin D

Abstract Objective: The mechanism of statin-related myopathy is unknown, while its prevalence is probably underestimated. An association between statin-related myopathy and vitamin D deficiency has been reported. In this pilot study we assessed the prevalence of myopathy in statin users attending the outpatient clinic of the Department of Cardiology of a University Hospital from October 2009 to March 2010. We also searched for predictors of myopathy and investigated whether the myopathy was associated with vitamin D deficiency. Research design and methods: Statin-treated patients were asked to complete an assisted structured questionnaire. Serum creatine kinase (CK) and 25-hydroxyvitamin D (25(OH)D) were measured. Patients with rheumatic diseases, muscle diseases, (poly)neuropathy and peripheral arterial disease were excluded from predictor analysis. Main outcome measures: Percentage of patients with myopathy in the daily clinical practice of an outpatient clinic, serum 25(OH)D, CK, and predictors of myopathy. Results: One hundred and four statin-treated patients completed the questionnaire. Serum 25(OH)D was measured in 93 patients. Twenty patients with confounding comorbidities were excluded from analysis. Of the remaining 84 patients, 33% reported myopathy, 24% had myalgia and 6% myositis. Rhabdomyolysis was not observed. Time spent outdoors during winter (≤6 h/week; OR: 10.61; 95% CI: 1.91–58.88), total number of prescribed drugs (1.39; 1.05–1.83), BMI (1.35; 1.07–1.69), CK (1.02; 1.00–1.03) and consumption of fish (≥1/week; 0.19; 0.04–0.89) were predictors of myopathy in multivariate analysis. Conclusions: Considering the small patient group and a relatively narrow range of vitamin D levels, we arrive at the following statements: 1) one out of three patients reported myopathy; 2) BMI, CK, number of prescription drugs, time spent outdoors and fish consumption were myopathy predictors; and 3) myopathy and 25(OH)D were unrelated.

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

IntroductionThe aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).MethodsThis is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.ResultsAfter three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physicians global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.ConclusionsThree years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.

Baseline predictors of response to TNF-α blocking therapy in ankylosing spondylitis.

Purpose of reviewIdentifying the characteristics of patients with ankylosing spondylitis (AS) before start of treatment which are able to predict a beneficial response to tumor necrosis factor-alpha (TNF-&agr;) blocking therapy is relevant, especially in view of the high costs and potential side-effects of these agents. This review provides an overview of clinical trials and observational studies investigating baseline predictors of response after 3–6 months of TNF-&agr; blocking therapy and baseline predictors of long-term anti-TNF-&agr; treatment continuation in AS. Recent findingsIn multiple studies, increased acute phase reactants, higher disease activity, higher functional status, younger age, and HLA-B27 positivity were identified as independent baseline predictors of achieving clinical response to TNF-&agr; blocking therapy. Increased acute phase reactants, presence of peripheral arthritis, and male sex were repeatedly identified as independent baseline predictors of anti-TNF-&agr; treatment continuation. SummarySeveral studies using multivariate analyses identified comparable baseline predictors of response and/or continuation of TNF-&agr; blocking therapy. The single predictors identified have, at best, moderate capacity to predict treatment response in the individual patient. The development of a prediction model may lead to a more robust instrument to support physicians in decision making on TNF-&agr; blocking therapy in AS in daily clinical practice.

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease

Background Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. Methods One hundred and nine patients with Crohns disease (CD) and 72 with ulcerative colitis (UC) (age 44.5±14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. Results Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. Conclusion The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.