Start Of Maintenance Treatment Research Articles

The M-ANNHEIM-AiP-Activity-Score is useful for predicting relapse in patients with type 1 autoimmune pancreatitis

Background/ObjectivesProper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP. MethodsWe retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment. ResultsMAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS<60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse. ConclusionsMAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.

Association of antidepressant drug use with outcome of patients with glioblastoma.

Depressive symptoms are common among patients with glioblastoma, but patients are often not treated with antidepressants. There is only limited evidence on the association of antidepressant drug use with survival in glioblastoma. We performed a pooled analysis of patients treated within the CENTRIC, CORE, AVAglio and ACT-IV trials to explore the relation of antidepressant drug use with progression-free (PFS) and overall survival (OS) at baseline, at the start of maintenance therapy and at the start of maintenance cycle 4. We further assessed the association of antidepressant drugs with seizure, cognition, fatigue and a diagnosis of depression. Among more than 1700 patients, we found no significant association between the use of antidepressants at baseline or at the start of maintenance therapy and PFS or OS. However, we found OS, but not PFS, to be significantly worse in patients using antidepressants at the start of maintenance cycle 4. After adjustment for antiepileptic drug use and despite showing a trend for increased risk, seizures were not significantly associated with antidepressant drug use, nor was there a change in mini mental state examination (MMSE) scores or fatigue by antidepressant drug use at baseline. However, there was a significant positive association between antidepressant use at the start of maintenance treatment and fatigue during maintenance treatment. The association of antidepressant use at the start of maintenance cycle 4 with inferior OS of glioblastoma patients requires independent confirmation and further study. Further prospective trials should evaluate efficacy, side effects and associations with outcome of antidepressants in glioblastoma.

The MaDo real-life study of dose adjustment of allergen immunotherapy liquid formulations in an indication of respiratory allergic disease: Reasons, practices, and outcomes.

Sublingual allergen immunotherapy (SLIT) is a safe, effective, disease-modifying treatment for moderate-to-severe respiratory allergies. The function and responsiveness of the immune system components underlying the effects of allergen immunotherapy may vary from one patient to another. Furthermore, the severity of the symptoms of allergic disease can fluctuate over time, due to changes in environmental allergen exposure, effector cell responsiveness, and cell signaling. Hence, the allergen dose provided through SLIT can be fine-tuned to establish an optimal balance between effectiveness and tolerability. The objective of the MaDo study was to describe and understand dose adjustments of SLIT liquid formulations in France. We performed a retrospective, observational, cross-sectional, real-life study of allergists and other specialist physicians. Physicians described their patients via an anonymous case report form (CRF). The main patient inclusion criteria were age 5 years or over, at least one physician-confirmed IgE-driven respiratory allergy, and treatment for at least 2 years with one or more SLIT liquid preparations. A nationally representative sample of 33 specialist physicians participated in the study. The physicians' main stated reasons for dose adjustment were adverse events (according to 90.9% of the physicians), treatment effectiveness (60.6%), sensitivity to the allergen (42.4%) and other characteristics (30.3%: mainly symptom severity, type of allergen, and asthma). 392 CRFs (mean ± standard deviation patient age: 27.8 ± 17.5; under-18s: 42.1%; polyallergy: 30.9%) were analyzed. Respectively 53.6%, 25.8%, 15.3%, and 8.7% of the patients received house dust mite, grass pollen, birch pollen and cypress pollen SLIT. Dose adjustments were noted in 258 (65.8%) patients (at the start of the maintenance phase for 101 patients (39.2%) and later for 247 (95.7%)). Dose adjustment was not linked to sex, age, or the number of allergens administered. All measures of disease severity (including symptom severity noted on a 0-to-10 visual analogue scale by the physician) decreased significantly during SLIT. Notably, the mean AR symptom severity score decreased to a clinically relevant extent from 7.6 at SLIT initiation to 2.4 at last follow-up, and the mean asthma symptom severity score decreased from 5.0 to 1.3. The few differences in effectiveness between patients with vs. without dose adjustment were not major. For about one patient in five, a specialist physician decided to reduce or increase the SLIT liquid dose at the start of maintenance treatment and/or during maintenance treatment. This decision was influenced by a broad range of patient and treatment factors, mainly to improve tolerability to treatment and/or enhance effectiveness. In France, dose adjustment of SLIT liquid preparations as a function of the patient profile and/or treatment response is anchored in clinical practice. Precision dosing might optimize the overall benefit-risk profile of AIT for individual patients throughout their entire treatment course, enabling them to achieve both short- and long-term treatment goals, whilst maximizing the safety and tolerability.

Brief Report: Exploratory Analysis of Maintenance Therapy in Patients With Extensive-Stage SCLC Treated First Line With Atezolizumab Plus Carboplatin and Etoposide

IntroductionIn the phase 1/3 IMpower133 study, atezolizumab plus carboplatin and etoposide (CP/ET) followed by maintenance atezolizumab for first-line treatment of extensive-stage SCLC (ES-SCLC) led to improvement in both overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET followed by maintenance placebo. We explored the benefit of atezolizumab versus placebo in the subset of patients who reached the IMpower133 maintenance phase and the safety profile of maintenance therapy. MethodsPatients with untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo, followed by maintenance atezolizumab or placebo. The primary end points were OS and investigator-assessed PFS. A multivariate Cox model from the start of maintenance treatment was used to evaluate the treatment effect and account for lead-time bias; a generalized linear model was used to identify prognostic or predictive characteristics for reaching the maintenance phase. ResultsA similar proportion of patients in each arm received at least the first dose of maintenance therapy (atezolizumab: 77%, n = 154 of 201; placebo: 81%, n = 164 of 202) and were included in the maintenance analysis population. An Eastern Cooperative Oncology Group performance status of 0 and absence of liver metastases at baseline were identified as prognostic factors for reaching the maintenance phase. The positive treatment effect with atezolizumab remained after adjusting for baseline characteristics. Median OS and PFS from the start of maintenance therapy in the atezolizumab versus placebo arm were 12.5 versus 8.4 months (hazard ratio = 0.59, 95% confidence interval: 0.43–0.80) and 2.6 versus 1.8 months (hazard ratio = 0.63 [95% confidence interval: 0.49–0.80]), respectively. Treatment-related adverse events from the start of maintenance therapy occurred in 41% (n = 64 of 155) and 25% (n = 41 of 163) of safety-evaluable patients in the atezolizumab and placebo arms, respectively, and were grade 3 or 4 in 28% (n = 43 of 155) and 23% (n = 37 of 163) of the respective populations; no patient in the atezolizumab arm and one patient in the placebo arm had a grade 5 treatment-related adverse event. ConclusionsThese data in the context of other immunotherapy trials in ES-SCLC suggest that induction with atezolizumab plus CP/ET and maintenance treatment with atezolizumab are important components that contributed to the OS benefit observed in IMpower133. Safety results from randomization and from the start of maintenance therapy were similar between the treatment arms despite the continuation of atezolizumab in the maintenance phase.

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma during Treatment with Ixazomib-Thalidomide-Dexamethasone Followed By Ixazomib Maintenance

Health-Related Quality of Life in Patients with Relapsed/Refractory Multiple Myeloma during Treatment with Ixazomib-Thalidomide-Dexamethasone Followed By Ixazomib Maintenance

Decreasing Dose and Duration of Dexamethasone Therapy for Low-Risk Childhood Acute Lymphoblastic Leukemia Aiming to Avoid Serious Viral Infections Results in Significant Increase in Isolated CNS Relapse: A Prospective Study

Background: In the era of treating childhood acute lymphoblastic leukemia (ALL) without cranial irradiation, optimization of central nervous system (CNS) active therapeutic agents is needed to prevent CNS relapse. Dexamethasone is an essential part of maintenance therapy in most current protocols for its excellent CNS penetration and anti-leukemic effect. The dose and duration of dexamethasone treatment for low-risk patients vary across trials. In our institution, we adopted the St Jude Total XV protocol with minor modifications since 2002. This treatment has resulted in 5-year OS and EFS rates of 96.4% and 94% respectively for low-risk patients. However, around 11% of patients developed serious viral infections, mainly disseminated varicella (6%), CMV retinitis (3.6%) and progressive multifocal encephalopathy (1.1%). The aim of this trial was to decrease the incidence of serious viral infections by decreasing the dose and the duration of dexamethasone treatment during maintenance therapy.Patients and Methods: This is a prospective, non-randomized trial of all consecutive low-risk ALL patients aged 1-18 years treated at the Children's Cancer Center of Lebanon that included patients diagnosed after June 2013 as well as patients diagnosed earlier who had not reached week 100 of maintenance therapy by June 2013. Low-risk patients were defined elsewhere [Muwakkit et al, Am J Hematol. 2012 Jul;87(7):678-83].For patients diagnosed after June 2013; dexamethasone dose was decreased by 25% (from 8 to 6 mg/m2/day for 5 days/week every 4 weeks) and dexamethasone pulses were stopped at week 69 instead of week 100 from start of maintenance therapy. For patients on therapy who had not reached week 69 of maintenance; dexamethasone pulses were stopped at week 69, and dexamethasone dose was decreased by 25% (from 8 to 6 mg/m2/day for 5 days/week every 4 weeks) starting June 2013. For patients who had completed 69 weeks but did not reach week 100 of maintenance by June 2013, dexamethasone pulses were stopped. The interval between dexamethasone pulses was 4 weeks for all patients, before and after the change.The number of intrathecal chemotherapy injections was not changed.For analysis, historical control patients who completed therapy before June 2013 and patients on therapy who completed more than half of their planned dexamethasone pulses (week 50) by June 2013 were assigned to group 1. Patients who were diagnosed after June 2013 and those who had received less than half of their planned dexamethasone pulses (week 50) by June 2013 were assigned to group 2.The trial was stopped in May 2017 due to the observed increased incidence of isolated CNS relapse in group 2.Results: The total number of patients was 84 in group 1 and 33 in group 2. There was no significant difference in patient characteristics between the two groups. After a median follow-up of 88 months (range: 24-177), the 4-year cumulative incidence of isolated CNS relapse increased from 0% in group 1 to 9.5% (n=3) (95% CI: 0-19.2%) in group 2 (P : 0.005). The mean cumulative dose of dexamethasone was 1129 mg/m2 (SD 49 mg/m2) for group 1 and 838 mg/m2 (SD 31 mg/m2) for group 2 (P : <0.001). The mean total duration of dexamethasone pulses from start of maintenance treatment was 97 weeks (SD 8 weeks) for group 1 and 69 weeks (SD 0 weeks) for group 2 (P <0.001). The cumulative dose of dexamethasone received by patients with isolated CNS relapse was 824, 876 and 930 mg/m2. The isolated CNS relapses occurred at weeks 74, 95 and 116 of maintenance therapy. None of the patients with isolated CNS relapse had an initial traumatic lumbar puncture. None of group 2 patients developed disseminated varicella, CMV retinitis, or progressive multifocal encephalopathy. None of the patients in both groups developed bone marrow relapse within 4 years of diagnosis. The 4-year cumulative incidence of infection-related mortality was 3.5% (95% CI: 0-7.4%) for group 1 and 0% for group 2 (P : 0.27). The 4-year OS rate was 96.4% (95% CI: 89.3-98.8%) for group 1 and 100% for group 2 (P : 0.27). The 4-year EFS rate was 96.4% (95% CI: 89.3-98.8%) for group 1 and 90.5% (95% CI: 73.2-96.8%) for group 2 (P : 0.24).Conclusions: Decreasing dose and duration of dexamethasone therapy for low-risk childhood ALL patients aiming to avoid serious viral infections led to significant increase in isolated CNS relapse. Further studies are needed to identify the optimal dose and duration of dexamethasone therapy for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Infliximab in young paediatric IBD patients: it is all about the dosing

Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IFX was started as IBD treatment at age < 10 years (young patients, YP) and PK data were available. Older IBD patients aged 10–18 years were used as controls (older patients, OP). Two hundred and fifteen paediatric inflammatory bowel disease (PIBD) patients were eligible for the study (110 < 10 year; 105 ≥ 10 years). Median age was 8.3 years (IQR 6.9–8.9) in YP compared with 14.3 years (IQR 12.8–15.6) in OP at the start of IFX. At the start of maintenance treatment, 72% of YP had trough levels below therapeutic range (< 5.4 μg/mL). After 1 year of scheduled IFX maintenance treatment, YP required a significantly higher dose per 8 weeks compared with OP (YP; 9.0 mg/kg (IQR 5.0–12.9) vs. OP; 5.5 mg/kg (IQR 5.0–9.3); p < 0.001). The chance to develop antibodies to infliximab was relatively lower in OP than YP (0.329 (95% CI − 1.2 to − 1.01); p < 0.001), while the overall duration of response to IFX was not significantly different (after 2 years 53% (n = 29) in YP vs. 58% (n = 45) in OP; p = 0.56).Conclusion: Intensification of the induction scheme is suggested for PIBD patients aged < 10 years.What is Known?•Infliximab trough levels of paediatric IBD patients are influenced by several factors as dosing scheme, antibodies and inflammatory markers.•In 4.5–30% of the paediatric IBD patients, infliximab treatment was stopped within the first year.What is New?•The majority of young PIBD (< 10 years) have inadequate IFX trough levels at the start of maintenance treatment.•Young PIBD patients (< 10 years) were in need of a more intensive treatment regimen compared with older paediatric patients during 1 year of IFX treatment.•The chance to develop antibodies to infliximab was relatively higher in young PIBD patients (< 10 years).

Talking about Dr. Google: Communication strategies used by nurse practitioners and patients with inflammatory bowel disease in the Netherlands to discuss online health information

ObjectiveThis study explores how patients with Inflammatory Bowel Disease (IBD) and nurse practitioners (NPs) in the Netherlands communicate about online health information-seeking. MethodsWe analyzed 165 consultations of patients at the start of maintenance treatment using grounded theory. Consultations in which the words; internet, website, Google, Googled, webpages, online (forum/blog/platform) or a website was mentioned, were included. Segments were identified and analyzed that represented a discussion about online health information-seeking (n = 87). We coded the initiator, initiation and reaction communication strategy. ResultsHalf of the sample was female, most patients were moderately to highly educated and aged on average 48 years. One third of the consultations included a discussion about online health information-seeking. Seventeen communication initiation and reactions strategies were identified. Patients and NPs were equally as likely to initiate a neutral discussion about online health information-seeking. Patients repeatedly reacted with disclosing their concerns. NPs responded by taking patients’ online health information-seeking seriously or affirming patients’ beliefs. ConclusionThis exploration makes a unique contribution by demonstrating that NPs particularly adopt a patient-centered communication style while communicating about patients’ online health information-seeking. Practice implicationsResults of this study could guide interventions to train providers in talking about patients’ online health information-seeking.

Protein array profiling of circulating angiogenesis-related factors during bevacizumab containing treatment in metastatic colorectal cancer.

BackgroundProlonged angiogenesis inhibition may improve treatment outcome in metastatic colorectal cancer (mCRC) patients. However, due to the complexity of the angiogenic pathways there is a lack of valid predictive biomarkers for anti-angiogenic agents. Here, we describe and optimize a procedure for simultaneous dynamic profiling of multiple angiogenesis related proteins in patient serum to explore associations with the response and acquired resistance to anti-angiogenic therapy.Materials and methodsPatients (n=22) were selected from a clinical trial investigating maintenance treatment with bevacizumab alone after response to induction chemotherapy + bevacizumab in mCRC. Serum samples were analysed for 55 unique angiogenesis related proteins using a commercial proteome profiler array and a publicly available image analysis program for quantification. Samples were collected at baseline before induction treatment start, at start of maintenance treatment, and at end of treatment after tumour progression.Main results and conclusionFor eight proteins, the antibody array signals were below detection range in all patient samples. None of the proteins showed levels at baseline or at start of maintenance with strong evidence for correlation to time to progression (lowest nominal p-value 0.03). The dynamic ranges of protein levels measured during the induction treatment period and during the maintenance period were analysed separately for time trends. Evidence for changing trends (up/down) in the levels of MMP-8, TIMP-4 and EGF was observed both during response to induction treatment and at progressive disease, respectively. For three of the proteins (IL-8, Activin A and IGFBP-2), weak evidence for correlation between increasing protein levels during induction with chemotherapy and bevacizumab and time to progression was observed.In conclusion, semi-quantitative profiling of angiogenesis related proteins in patient serum may be a versatile tool to screen for protein patterns aiming at identifying resistance mechanisms of anti-angiogenic treatment in patients with mCRC.

On-demand versus half-dose continuous therapy with esomeprazole for maintenance treatment of gastroesophageal reflux disease: A randomized comparative study.

Background and aims:No consensus has been established regarding optimal long-term maintenance therapy in symptomatic gastroesophageal reflux disease (GERD). The aim of this study was to compare the efficacies of on-demand and continuous therapy with esomeprazole as maintenance treatments for GERD.Methods:Patients with upper gastrointestinal (GI) endoscopy-proven GERD who received initial proton pump inhibitor (PPI) therapy for 8 weeks were randomized to an on-demand group (esomeprazole 40 mg) or a continuous group (esomeprazole 20 mg). Intensities and frequencies of heartburn and acid regurgitation were assessed using a 6-point Likert scale (0 = no symptoms; 5 = very severe symptoms) and a 6-point frequency scale (0 = none; 5 = symptoms for > 5 days per week) at baseline (start of maintenance treatment) and after 12 weeks of treatment. Alleviation of symptoms was quantified using percentages of patients with a Likert scale or frequency scale of 0 or 1.Results:Of the 88 patients enrolled, 8 patients were excluded due to follow-up loss in early period of this study, and finally, 39 in the on-demand group and 41 in the continuous group were analyzed. No significant intergroup difference was found between Likert scale or frequency scale of heartburn or regurgitation at baseline. Percentages of symptom alleviations in the on-demand and continuous groups for intensity of heartburn were 56.4%/48.8% at baseline (P = .523) and 82.1%/87.8% at 12 weeks (P = .471), for frequency of heartburn were 61.5%/46.3% at baseline (P = .173) and 76.9%/87.8% at 12 weeks (P = .200), for intensity of regurgitation was 53.8%/43.9% at baseline (P = .374) and 82.1%/87.8% at 12 weeks (P = .471), and for frequency of regurgitation was 61.5%/56.1% at the baseline (P = .621) and 82.1%/82.9% at 12 weeks (P = .918), respectively. Furthermore, no significant intergroup difference was found for convenience of medication or subjective satisfaction.Conclusions:Intensities and frequencies of heartburn and regurgitation responded well to maintenance treatment in patients in the on-demand and continuous groups. On-demand therapy with esomeprazole 40 mg appears to be sufficient for maintenance treatment in GERD patients.

Tu1122 Optimal Dosing of Mesalamine for Maintenance of Clinical Remission in Patients With Distal Ulcerative Colitis and Residual Endoscopic Activity: A Subgroup Analysis of a Double-Blind, Double-Dummy, Randomized, Controlled, Dose-Ranging Study

Introduction: Proctosigmoiditis is the most frequent phenotype of ulcerative colitis (UC). Recently, it has been shown that 3 g oral mesalamine (Salofalk® granules) once daily (OD) showed higher rates for maintaining remission compared to lower doses of mesalamine, especially in patients with residual signs of endoscopic inflammatory activity at the start of the treatment.1 But, whether patients with proctosigmoiditis and residual endoscopic inflammation might profit from a higher dose is unclear. Aims: To study optimal dosing of mesalamine for maintenance of remission in proctosigmoiditis with residual endoscopic activity at the start of treatment. Methods: This was a stratified subgroup analysis of a double-blind, double-dummy, randomized, multicenter, comparative phase III study, in which the clinical outcome (i.e., clinical remission at wk 52) was analyzed in patients with proctosigmoiditis according to the presence of residual endoscopic inflammation at the start of maintenance treatment. Patients with active UCwho had recently achieved clinical (Clinical Activity Index [CAI] ,= 4) and an endoscopic index (EI) ,= 3 were randomized to mesalamine (Salofalk® granules) 3g OD, 1.5g OD, or 0.5g TID for 12 months. Remission at study end was defined as a CAI of ,= 4 with no increase of .=3 points from baseline. Results: A total of 647 patients who came into remission within the last 12 weeks prior to baseline were randomized and treated; 217 patients with 3g OD, 212 with 1.5g OD, and 218 with 0.5g TID mesalamine. All three treatment regimens were efficacious in maintaining clinical remission of UC over 1 year. A subgroup analysis in patients with vs. without residual mucosal damage showed that 3g OD performed best in the subgroup with residual inflammation at start of treatment. A further subgroup analysis of patients with residual mucosal damage according to extent of UC revealed that 3g OD performed best independently from the extent (see table below). Conclusions: A dosage of 3g mesalamine (Salofalk® granules) once daily showed the best efficacy for prevention of relapse in UC compared to a daily dose of 1.5g mesalamine, especially in patients with residual signs of inflammation, even in the distal colon. Reference: (1) Kruis W, Jonaitis L, Pokrotnieks J, Mikhailova TL, Horynski M, Batovsky M, et al. Aliment Pharmacol Ther. 2011;33(3):313-22. Support: Dr. Falk Pharma GmbH, Freiburg, Germany Clinical remission by mucosal damage and extent of mucosal damage (ITT):

Quality of life of patients and medical cost of “half elemental diet” as maintenance therapy for Crohn’s disease: Secondary outcomes of a randomised controlled trial

Quality of life (QOL) of the patients and medical costs are important in current medical treatments, especially those for chronic diseases. We have reported the effectiveness of 'half elemental diet (ED)' as maintenance therapy for patients with Crohn's disease (CD). The aim of this study was to evaluate the QOL of CD patients and medical costs of half-ED. Fifty-one CD patients in remission were randomly assigned to a half-ED group (n=26) or a free diet group (n=25). The primary outcome measure was the occurrence of relapse during a 2-year period. This time, we investigated the QOL of the patients and medical costs of half-ED, as secondary outcomes. QOL was evaluated using the Japanese version of the IBDQ scoring system, and medical costs were calculated monthly from the receipts. IBDQ score was not significantly different between the two groups at 1 and 13 months after the start of maintenance treatment. Medical costs were not significantly different between them either. This study showed that half-ED therapy did not affect the treatment of CD patients, neither regarding their QOL nor medical costs. This study has confirmed this half-ED therapy is beneficial for patients with Crohn's disease.