Stable Maintenance Therapy Research Articles

P1088 Positive effects of a mindfulness-based intervention on depression, stress and perceived control, but not on disability in patients with Crohn’s disease: results from a randomized controlled trial

Abstract Background Crohn’s disease (CD) often leads to significant disability and psychological distress, significantly reducing patients’ quality of life. We evaluated the impact of a mindfulness-based intervention on disease-related disability in patients with CD on stable maintenance therapy. Additionally, we wanted to assess the impact of mindfulness on anxiety, depression, stress, disease acceptance, perceived control, and disease activity. Methods We conducted a monocentric randomized controlled trial (RCT), where participants were randomly assigned to an immediate intervention group or a waitlist control group that received the same intervention after six months. The IBD Disability Index at baseline (IBD-Disk ≥40 or <40) was used as a stratification factor. Disease activity was assessed through patient-reported outcomes (PRO-2) and biomarkers (faecal calprotectin and C-reactive protein), measured at baseline, at 1.5 and at 3 months follow-up. Psychological factors including anxiety, depression, and stress were assessed with the DASS21 scale. Disease acceptance and perceived control were measured using the SHE model, and mindfulness levels were assessed with the FFMQ-SF. The intervention consisted of a total of four mindfulness group sessions of three hours each over six weeks. The primary outcome was the mean change in the total IBD-Disk score at three months and was analysed using a constrained longitudinal data analysis (cLDA). Based on power calculation (α=0.05, power=0.80), 54 patients had to be randomized. Results As shown in Table 1, 56 patients (38% male, median age 49.5 years) were randomized into the immediate intervention group (n=28) or the six-month waitlist control group (n=28). Two patients dropped out in each group before reaching the primary endpoint. Compared to the waitlist, participants in the intervention group showed significant improvements in depression, stress, perceived control, and mindfulness after three months (see Table 2). Although improvements in disease-related disability, anxiety, and disease acceptance showed positive trends, these items did not reach statistical significance. No changes were observed in clinical and biochemical markers of disease activity. Conclusion A 6-weeks mindfulness-based intervention can significantly improve depression, stress, perceived control, and mindfulness in patients with CD, with effects sustained 3 months post-intervention. Although numerically better, no significant effects were found on disease-related disability. Further research is warranted to explore the long-term benefits and underlying mechanisms of mindfulness in CD management.

P353 Optimal Interval for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Stable Infliximab Maintenance Treatment

Abstract Background Recent studies suggest that proactive therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) improves clinical outcomes. However, as proactive TDM may lead to increased medical costs, we aimed to determine the optimal interval for TDM during infliximab maintenance therapy in IBD patients. Methods We conducted a retrospective analysis of a prospective cohort comprising 103 patients with IBD on IFX maintenance therapy who went through proactive TDM between February 2020 and May 2023. Following dose optimization till achieving a therapeutic trough level (TL) of 3 to 10 ug/mL, we applied the Kaplan-Meier (KM) method to calculate the time to subtherapeutic IFX TL (two consecutive IFX TLs below 3 ug/mL). Results 90% of patients had a sustained therapeutic IFX TL for 10.3 months, whilst 80% had it for 14.3 months. In multivariable analysis, IFX TL at enrollment had a association with the risk of subtherapeutic IFX TL (P=0.025). Persistence rates for therapeutic IFX TL were significantly lower in patients with IFX TL from 3 to 5 µg/mL at recruitment than in those with IFX TL >5 µg/mL (P=0.017). For patients who had IFX TL between 3 to 5 µg/mL upon enrollment, the percentage of those who maintained therapeutic IFX TL was 80% after 12.0 months. The group with IFX TL greater than 5 µg/mL had a persistence rate of 90% after 12.3 months. Conclusion These results suggest that conducting annual measurement of IFX TL in patients with IBD who are on stable maintenance therapy with IFX, which may reduce the cost of proactive TDM.

Biochemical differences between high and low dose methadone clients on stable maintenance therapy

The methadone dose required to prevent withdrawal symptoms in chronic methadone users varies dramatically from 5 to 300 mg/day, which could be attributed to a number of biochemical factors, including human µ-opioid receptor (hMOR) density, down-stream desensitization, concurrent drug use or P-glycoprotein (P-gp) expression, or other, possibly genetic factors. Here we describe some biochemical changes of patients taking higher versus lower doses in chronic methadone maintenance therapy (MMT). hMOR density was measured in leukocytes from methadone-maintained patients receiving lower dose (<100 mg/day) or higher dose (≥100 mg/day) and naive subjects by flow cytometry. Desensitization of receptor signaling was examined by measuring in vivo and attenuated cyclic AMP (cAMP) levels in response to increasing methadone concentrations. P-gp expression and the presence of other drugs were measured using validated methods.

Real-World Study on Vedolizumab Serum Concentration, Efficacy, and Safety after the Transition from Intravenous to Subcutaneous Vedolizumab in Inflammatory Bowel Disease Patients: Single-Center Experience.

Little is known about how the change from intravenous to subcutaneous vedolizumab in a real-life setting in inflammatory bowel disease patients on stable maintenance therapy affects clinical outcomes. We compared the data on vedolizumab serum trough concentration, efficacy, and safety prior to and six months after the switch from intravenous to subcutaneous vedolizumab. In total, 24 patients, 13 with ulcerative colitis (UC) and 11 with Crohn's disease (CD), were included. Mean serum trough concentration of intravenous vedolizumab was significantly lower than mean serum trough concentration of subcutaneous vedolizumab (p = 0.002). There was no significant difference between C-reactive protein levels, fecal calprotectin levels or clinical scores (Harvey-Bradshaw index or Partial Mayo score) prior to transition to subcutaneous vedolizumab and after 6 months. In four (16.7%) patients, two CD and two UC, therapy was discontinued during the follow-up period with a median of 5 months (minimum-maximum: 4-6). In all patients, therapy was discontinued due to loss of response. In total, 13 adverse events were reported by 11 patients, and the most common adverse event was COVID-19. No serious adverse events were reported. In conclusion, subcutaneous vedolizumab has shown to be effective and safe in patients on previously established maintenance therapy with intravenous vedolizumab.

A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study.

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8–19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30–40) at baseline to 12.5 (5–30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0–1880.0) μg/g at baseline to 592.0 (140.7–1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

Biochemical Differences Between High and Low Dose Methadone Clients on Stable Maintenance Therapy

Biochemical Differences Between High and Low Dose Methadone Clients on Stable Maintenance Therapy

P492 The UC Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A prospective open label pilot study

Abstract Background Strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). The goal of the pilot trial was to evaluate the efficacy of a novel microbe-directed UC diet (UCD) for clinical remission, as well as use of antibiotics for dietary refractory patients as an alternative strategy for remission. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores &amp;gt;10 on stable maintenance therapy. Patients failing to enter remission (PUCAI&amp;lt;10) on diet could receive a 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention to treat (ITT) remission at week 6 with UCD. Results Twenty-four UCD treatment courses were given to 23 eligible children (mean age 15.3±2.9 years). Median PUCAI decreased from baseline 35 (30–40) to 12.5 (5–27.5) week 6 (P=0.001). Clinical remission with UCD alone was achieved in 9/24 (37.5%). Median calprotectin declined from baseline 818 (630.0–1880.0) to 592.0 (140.7–902.4) week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion The UC Diet appears to be effective for induction of remission in children with mild to moderate UC suggesting that diet could play a role in the disease. Sequential use of UCD followed by antibiotic therapy needs to be evaluated as a microbiome targeted steroid sparing strategy.

EVALUATION OF A DIET AND ANTIBIOTICS TARGETING THE MICROBIOTA FOR TREATMENT OF MILD TO MODETARE ACTIVE PEDIARTIC ULCERATIVE COLITIS: AN OPEN LABEL PILOT STUDY

Abstract Background Newer strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). We developed a novel diet that targets changes in the microbiome and barrier function that have been reported in UC. The goal of the current study was to evaluate the efficacy of two sequential induction of remission strategies that target the microbiota: the novel diet termed the ulcerative colitis diet (UCD) and an antibiotics cocktail combination in dietary non responders. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores &amp;gt;10 and ≤45 on stable maintenance therapy (5ASA or thiopurines). PUCAI score was assessed at week 3 and 6. Patients failing to enter remission or intolerant to dietary therapy could receive an open label 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and had PUCAI scored at day 21. Response was defined a decline in PUCAI ≥ 10 points, remission as PUCAI&amp;lt; 10. The primary endpoint was intention to treat (ITT) remission at week 6 with diet as the sole intervention. Results Twenty-three children mean age of 15.1±2.9 years were enrolled. Two patients (1 responder, 1 remission) withdrew by 3 weeks, four required additional therapy by week 3, all were considered failures by ITT. Mean PUCAI decreased at week 3 and 6 from 34.5±9.8 to 21.7±14.9 and 17.6±17.2 respectively (P=0.005, P=0.001) at ITT analysis including all patients. Sixteen out of twenty-three patients (69.6%) responded by week 6. Ten of twenty-three (43.5%) achieved remission by week 6, and nine (39.1%) had clinical remission at week 6. The median fecal calprotectin (FC) level decreased in patients (n=5) who achieved remission from 630 (IQR, 332–1586) μg/g at week 0 to 230 (75–1298) μg/g at week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission. Conclusion A dietary intervention called the UC Diet appears to be effective for induction of remission in children with mild to moderate UC. Sequential use of diet, followed by antibiotic therapy in dietary non responders, needs further evaluation as a microbiome directed steroid sparing therapy in patient’s refractory to 5ASA and thiopurines.

Fluctuations in serum levels of adalimumab and infliximab in patients on stable treatment for psoriasis.

Many patients with psoriasis fail to respond to biologic drugs either initially or lose response over time, the latter having predominantly been linked to low circulating drug levels. We examined how serum drug levels varied over three treatment cycles of stable maintenance therapy with either adalimumab or infliximab among a total of 28 patients with psoriasis (22 men, mean age 48.6 years, mean treatment time 6.2 years) and whether there was an association with various patient-specific factors. The range for all concentrations was 1.1 to 24.3 μg/mL for adalimumab and 0.0 to 180.6 μg/mL for infliximab. There was a consistent inverse association between body mass index (BMI) and trough and maximum serum concentrations of adalimumab (P < .05 for all comparisons) and a positive, less consistent, association between age and maximum serum concentration of infliximab (P < .05 for both comparisons). Patient-specific factors, such as BMI and age, can help predict fluctuations in serum concentrations of biologics used for psoriasis.

Wide variation in the use and understanding of therapeutic drug monitoring for anti-TNF agents in inflammatory bowel disease: an inexact science?

ABSTRACTBackground: We aimed to understand the way in which therapeutic drug monitoring (TDM) is used, understood and interpreted for anti-TNF agents in IBD.Research design and methods: We designed an 18-question survey that included 5 TDM-based clinical scenarios, for which the ‘most appropriate’ responses were based on the BRIDGe groups ‘Anti-TNF Optimizer’. This resource combines TDM evidence with expert consensus.Results: We received 110 complete responses: 50 (45%) consultants, 30 (27%) trainees, 25 (23%) IBD nurse specialists and 5 (5%) gastroenterology pharmacists. Over half (61, 55%) only carry out TDM in non-response. The remainder use TDM routinely, including during stable maintenance therapy for patients in remission. Lower therapeutic thresholds used were variable. Most (82, 75%) were unsure whether their laboratory uses a drug-tolerant or drug-sensitive antidrug antibody assay and few (15, 14%) understand the difference. Consultants, high-frequency users (> 3requests/month) and clinicians with larger anti-TNF cohorts (> 100) were significantly more likely to select the ‘most appropriate’ answer to at least 1 of the 5 TDM-based clinical scenarios.Conclusions: There exists marked heterogeneity in the practical use, understanding and interpretation of biologic TDM. Biologic decision-making, informed by TDM, should involve consultation with experienced clinicians who are frequent TDM users, ideally, as part of a multidisciplinary, biologics-focused IBD meeting.Abbreviations: TDM: therapeutic drug monitoring; CNS: clinical nurse specialist; ELISA: enzyme-linked immunosorbent assay; RIA: radioimmunoassays; HMSA: homogenous mobility shift assays; BSG: British Society of Gastroenterology.

Atorvastatin-induced necrotizing autoimmune myositis: An emerging dominant entity in patients with autoimmune myositis presenting with a pure polymyositis phenotype.

The general aim of this study was to evaluate the disease spectrum in patients presenting with a pure polymyositis (pPM) phenotype. Specific objectives were to characterize clinical features, autoantibodies (aAbs), and membrane attack complex (MAC) in muscle biopsies of patients with treatment-responsive, statin-exposed necrotizing autoimmune myositis (NAM). Patients from the Centre hospitalier de l’Université de Montréal autoimmune myositis (AIM) Cohort with a pPM phenotype, response to immunosuppression, and follow-up ≥3 years were included. Of 17 consecutive patients with pPM, 14 patients had a NAM, of whom 12 were previously exposed to atorvastatin (mean 38.8 months). These 12 patients were therefore suspected of atorvastatin-induced AIM (atorAIM) and selected for study. All had aAbs to 3-hydroxy-3-methylglutaryl coenzyme A reductase, and none had overlap aAbs, aAbs to signal recognition particle, or cancer. Three stages of myopathy were recognized: stage 1 (isolated serum creatine kinase [CK] elevation), stage 2 (CK elevation, normal strength, and abnormal electromyogram [EMG]), and stage 3 (CK elevation, proximal weakness, and abnormal EMG). At diagnosis, 10/12 (83%) patients had stage 3 myopathy (mean CK elevation: 7247 U/L). The presenting mode was stage 1 in 6 patients (50%) (mean CK elevation: 1540 U/L), all of whom progressed to stage 3 (mean delay: 37 months) despite atorvastatin discontinuation. MAC deposition was observed in all muscle biopsies (isolated sarcolemmal deposition on non-necrotic fibers, isolated granular deposition on endomysial capillaries, or mixed pattern). Oral corticosteroids alone failed to normalize CKs and induce remission. Ten patients (83%) received intravenous immune globulin (IVIG) as part of an induction regimen. Of 10 patients with ≥1 year remission on stable maintenance therapy, IVIG was needed in 50%, either with methotrexate (MTX) monotherapy or combination immunosuppression. In the remaining patients, MTX monotherapy or combination therapy maintained remission without IVIG. AtorAIM emerged as the dominant entity in patients with a pPM phenotype and treatment-responsive myopathy. Isolated CK elevation was the mode of presentation of atorAIM. The new onset of isolated CK elevation on atorvastatin and persistent CK elevation on statin discontinuation should raise early suspicion for atorAIM. Statin-induced AIM should be included in the differential diagnosis of asymptomatic hyperCKemia. Three patterns of MAC deposition, while nonpathognomonic, were pathological clues to atorAIM. AtorAIM was uniformly corticosteroid resistant but responsive to IVIG as induction and maintenance therapy.

Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid under naturalistic conditions

Introduction: To investigate whether drug concentrations in plasma can be considered as a valid surrogate marker of concentrations in brain/cerebrospinal fluid, the concentrations of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in plasma and cerebrospinal fluid (CSF) were measured in 18 patients diagnosed with a depressive Episode in stable maintenance therapy. Method: The present study is a naturalistic prospective investigation of 18 depressive patients treated daily doses of venlafaxine extended release in a dose range between 75 and 300 mg. Patients underwent lumbar puncture (LP) for medical reasons and not for the purpose of this study. Blood was collected in at the same time as lumbar puncture was done. LP was done as part of the clinical routine without placing a special emphasis on trough levels of the ingested drug. Results: Plasma-levels of VEN were in a range between 10 and 1,269 ng/mL, ODV was in a range between 1 and 456 ng/mL. VEN + ODV (active moiety) correlated significantly with the oral venlafaxine dose (plasma: r =+0.810, p < 0.01; Pearson's correlation). CSF-levels were between 0 and 945 ng/mL for VEN, and 0 and 380 ng/mL for ODV. The correlation between plasma levels of VEN + ODV (active moiety) and the daily oral venlafaxine dose was highly significant and the correlation between the active moiety in plasma and CSF as well. Conclusion: The preliminary data of this ongoing study highlight the penetration of VEN and its active metabolite ODV into the CSF. In recent times, only few studies have addressed the question as to which extent plasma concentrations of psychotropic drugs correlate with CSF levels and knowledge is lacking concerning the impact of different drug levels in CSF on clinical outcome or on (cellular) homaeostasis within the CSF. The presented data show that in case of VEN and ODV, plasma concentrations can be considered as a valid surrogate marker of concentrations in CSF and possibly at its target structures inside the brain

Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing

Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (>6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) ≥4 (primary end point) and the percentage of patients with a maximum GFSS of ≥4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of ≥4 (p <0.001) and the percentage of patients with a maximum GFSS of ≥4 (p <0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.

PTU-129 Initial experience with infliximab levels in a tertiary IBD centre

IntroductionBiologic use in the UK is increasing in patients with Crohn's disease (CD). While highly effective at inducing and maintaining remission, secondary loss of response occurs in approximately 15% of...

Epoetin theta: efficacy and safety of subcutaneous administration in anemic pre-dialysis patients in the maintenance phase in comparison to epoetin beta

Objective:To compare the efficacy and safety of epoetin theta and epoetin beta in anemic patients with chronic kidney disease (CKD) not yet receiving dialysis and previously on stable maintenance therapy with epoetin beta.Methods:In this multicenter, randomized, controlled, double-blind, non-inferiority study, 288 patients were treated subcutaneously (s.c.) for 24 weeks with epoetin theta (n = 193) or epoetin beta (n = 95). The primary efficacy endpoint was change in hemoglobin (Hb) from a 2-week baseline period to end of treatment (12-week efficacy evaluation period [EEP], weeks 15–26). The non-inferiority limit was 1.0 g/dL (2-sided alpha = 0.05). Weekly doses of epoetin required to maintain Hb levels, dose changes, safety, tolerability, and immunogenicity were also evaluated.Clinical trial registration:EudraCT No. 2005-000142-37Results:Mean Hb values were comparable in both groups at baseline and during the 24-week treatment period. The estimated treatment difference between groups from baseline to EEP was 0.01 g/dL (95% confidence interval: −0.20, 0.22; p = 0.9207 (ANCOVA)), indicating that epoetin theta was non-inferior to epoetin beta. The weekly doses of epoetin theta or epoetin beta were nearly the same and the change from baseline to EEP in patients who switched to epoetin theta (36.6 to 30.0 IU/kgBW) was comparable to those continuing epoetin beta therapy (37.7 to 28.3 IU/kgBW). The profile and the frequency of adverse drug reactions (ADRs) were comparable in both groups (17.1% epoetin theta; 14.7% epoetin beta). The most common ADR was hypertension. No patient developed anti-erythropoietin antibodies.Conclusions:Epoetin theta (s.c.) has efficacy comparable with epoetin beta (s.c.) in pre-dialysis patients with renal anemia based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was also comparable. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.

Abstract 8824: Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients

Extended-release niacin (ERN) produces improvements across the lipid profile in patients with dyslipidemia, but is underutilized due to flushing, a process primarily mediated by prostaglandin D 2 (PGD 2 ). The PGD 2 receptor antagonist, laropiprant (LRPT), reduces ERN-induced flushing in patients with dyslipidemia. This study tested the hypothesis that, after 20 weeks of the fixed-dose combination ERN/LRPT, patients who continued on ERN/LRPT would have less flushing than patients who had LRPT withdrawn, but continued on ERN alone. After a 2-week placebo run-in, 1152 patients with dyslipidemia were randomized 2:2:1 to one of three daily treatment groups: (1) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg for the remainder of the study; (2) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg from 5 to 20 weeks, then ERN 2g without laropiprant from 21 to 32 weeks; or (3) placebo for the duration of the study. The key endpoints were based on the Global Flushing Severity Score (GFSS) from the previously validated Flushing Symptom Questionnaire: the number of days/week with moderate or greater GFSS ≥4 (primary) and the percentage of patients with maximum GFSS ≥4 (secondary) during the post-withdrawal period of the study (weeks 21 to 32). ERN/LRPT produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p&lt;0.001; see fig) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%). There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups. In summary, following 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less flushing than patients who had LRPT withdrawn, and continued with ERN alone. This study supports the long-term efficacy (&gt; 24 weeks) of ERN/LRPT in reducing flushing symptoms.

Epoetin theta: efficacy and safety of IV administration in anaemic haemodialysis patients in the maintenance phase in comparison to epoetin beta

Objective:To compare the efficacy and safety of epoetin theta and epoetin beta in anaemic patients with chronic kidney disease, undergoing haemodialysis and previously on stable maintenance therapy with epoetin beta.Methods:In this multicentre, randomised, controlled, double-blind study 270 haemodialysis patients were treated intravenously (i.v.) for 24 weeks with either epoetin theta (n = 180) or epoetin beta (n = 90). The primary efficacy endpoint was the change in haemoglobin (Hb) from baseline to end of treatment (efficacy evaluation period, EEP, weeks 15–26). Hb levels, weekly doses of epoetin theta or epoetin beta required to maintain Hb levels, dose changes, safety, tolerability and immunogenicity were evaluated.Clinical trial registration: EudraCT No. 2005-000143-28Results:Mean Hb values were similar in both treatment groups at baseline and during the 24-weeks treatment period. The estimated treatment difference between epoetin theta and epoetin beta from baseline to EEP was −0.01 g/dL (95% confidence interval: −0.24, 0.21), p = 0.9021, indicating that the difference between both groups was not statistically significant. The weekly doses of epoetin theta or epoetin beta required to maintain Hb levels were nearly the same. The changes from baseline to EEP in patients who switched to treatment with epoetin theta (95.5–99.7 IU/kgBW) were smaller than in patients staying on their epoetin beta therapy (89.0–98.0 IU/kgBW). The profile and the frequency of adverse drug reactions (ADRs) were similar in both treatment groups (21.7% epoetin theta; 22.2% epoetin beta). The most common ADRs were hypertension, headache and arteriovenous fistula thrombosis. None of the patients developed anti-erythropoietin antibodies.Conclusions:Epoetin theta (i.v.) has a similar efficacy compared to epoetin beta (i.v.) in haemodialysis patients based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was similar in both groups. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Frequency of relapses in patients with polymyositis and dermatomyositis.

The frequency of clinical and biochemical relapses was determined in a group of 50 patients with polymyositis (PM), dermatomyositis (DM), or overlap syndromes who were followed for periods of up to 13 years. Relapses occurred in 30 of the 50 patients (60%) during the period of follow-up. The annual relapse rate was not significantly different in the three groups of patients. Subclinical relapses occurred in each group but were less frequent in the DM than in the PM and overlap groups. Relapses could occur at any time but were more frequent during periods of stable maintenance therapy. There was no correlation between relapses and initial disease severity, delay to diagnosis and commencement of treatment, or any class I or II histocompatibility locus antigen.

Practical approach to quality of life in Parkinson's disease: the nurse's role.

In recent years it has become apparent that nurses have several key roles in the treatment of Parkinson's disease. These include the practice of skilled clinical care, the provision of advice and education, communicating with patients and carers, and also between health and social care agencies. Their goals are to facilitate good clinical care, to reduce morbidity (both physical and psychological) and to achieve better informed patients by the reduction of misinformation, fear and distress caused by the diagnosis and consequences of this disease. The overall goal is to improve the prognosis and to reduce the impact of this disease on patients and their care givers. To achieve these goals the specialist nurse needs skills in assessment, reassessment and counselling in addition to knowledge of the disease and its management. The training needs have been established for the nursing profession to address these issues, and courses have been established and approved. A scale comprising four clinical management stages has been proposed: initially around the time of diagnosis; stable maintenance therapy; a more complex management stage, and palliative care. Nursing interventions and priorities differ in these arbitrary stages. Several models of nursing provision have been piloted in the United Kingdom, and results of evaluations are keenly awaited. Meanwhile, specialist nurses are proving to be popular with patients and carers, medical specialists, and the Parkinson's Disease Society which aims to see their provision in each Health District throughout the United Kingdom. In summary, the nursing role is complementary to those of the other members of the multi-disciplinary health team that aims to improve the quality of life of PD patients and their carers.