Reasons For Cessation Of Treatment Research Articles

Navigating the discontinuation of multiple sclerosis first line treatments: A paradigm shift in patient care

BackgroundThis retrospective study, conducted between 2005 and 2016, investigated the outcomes of patients with multiple sclerosis (MS) who discontinued injectable first-line disease-modifying therapies (DMTs). The study aimed to identify factors influencing treatment discontinuation and assess the impact of discontinuation on disease progression. MethodsData was collected from 2,270 patients who received injectable DMTs for at least two years and subsequently discontinued treatment due to clinical and MRI remission, side effects, or noncompliance. Patients were categorized into two groups: those stable after discontinuation (SAD) and those with relapse after discontinuation (RAD). Survival analysis and logistic regression were employed to assess factors influencing treatment discontinuation. ResultsOf the 60 patients who discontinued DMTs, one-third (n = 20) remained stable, while 40 patients experienced clinical and/or MRI activity during follow-up. The SAD group had a significantly later age at treatment discontinuation compared to RAD patients (35.9 ± 11.1 vs. 30.7 ± 6.1, p = 0.025). Patients below 40 years old had a higher likelihood of experiencing worsening (75 %), while those over 50 years old demonstrated an 80 % stability rate. SAD patients used DMTs for a more extended period than RAD patients (69.1 ± 47.3 vs. 46.6 ± 20.3 months, p = 0.012). A notable proportion (42.9 %) of worsened patients discontinued DMTs without consulting a physician, emphasizing potential challenges in treatment adherence. After treatment discontinuation, RAD patients experienced relapses after a median of 21.0 months. Survival analysis suggested a more favorable disease course for patients who discontinued treatment after achieving a stable period (p = 0.237), with evidence of differentiation between groups after four years. Regression analysis indicated that older age at discontinuation had a favorable impact on relapse probability (HR: 0.904; p = 0.031; 95 % CI: 0.825, 0.991). Reasons for discontinuation unrelated to disease stability showed a positive but imprecise effect on relapse probability. ConclusionThis study provides insights into the outcomes of MS patients discontinuing injectable DMTs, emphasizing the importance of age at discontinuation and reasons for treatment cessation in predicting disease progression. The findings suggest that discontinuation after achieving stability may lead to more favorable outcomes, highlighting the need for personalized treatment decisions in MS management. Further research is warranted to validate these findings and inform clinical practices.

P718 Observational real-world evidence on the efficacy and safety of Janus Kinase inhibitors (JAKi) in the treatment of moderate to severe Active Ulcerative Colitis (UC)

Abstract Background Janus kinase inhibitors (JAKi) are the first orally administered treatment for Ulcerative Colitis (UC). The JAK family comprises of four intracellular tyrosine kinases inhibitors (JAK1, JAK2, JAK3 and Tyrosine Kinase 2). Inhibition of the JAK kinases lead to dampening of the inflammatory cytokines which drive Inflammatory Bowel Disease (IBD). Tofacitinib was the first generation pan-JAKi. This was followed by second generation JAKi: Filgotinib and Upadacinib which preferentially inhibit JAK1. We report on the real-world evidence on the efficacy and safety of JAKi in the treatment of UC in a tertiary IBD treatment centre. Methods Patients attending the IBD clinic at weeks 8-12 of initiation of therapy were included. Baseline demographics, disease activity and previous therapies were recorded. Clinical response was measured using the SCCAI and biochemical response was measured using calprotectin and CRP. We defined clinical response as ≥3 points reduction from baseline SCCAI, and clinical remission as SCCAI Score of <2.5, and / or biochemical remission as a CRP of less than 5 mg/L and a calprotectin level of < 250 mg/g. We also assessed treatment persistence, and the reasons for treatment cessation. Results The UC populations are shown in Table 1. 52 patients were included and an additional 24 patients who discontinued therapy early on were assessed to review secondary outcomes. Table 1 summarises the comparative outcomes of the JAKi. 81% and 63% of patients achieved clinical and biochemical remission respectively. Overall, 31% discontinued treatment due to lack of efficacy or adverse events. 60% of patients reported adverse events (AEs), 25 % of patients discontinued treatment due to AEs and 84% of patients continued treatment despite reporting AEs. The most common AEs were hypercholesteremia and cold and flu like symptoms and the most common AEs related with treatment discontinuation were recurrent infection or persistent deranged liver functions contributed to patients’ history of primary sclerosing cholangitis. No Serious Adverse Events were reported. 60% of patients on tofacitinib developed side effects and persisted with therapy, which included hypercholesteremia (67%), shingles (11%), flu like symptom (11%) and hair loss (11%). 53% had side effects with Filgotinib; hypercholesteremia (25%), cold like symptoms (25%), chest infection (13%), shingles (13%), acne (13%). 68% developed side effects with Upadacitinib; reports of acne (20%), cold and flu (33%), shingles and mood swings (7%) and high cholesterol (67%). Conclusion In this real-world cohort of UC patients, JAKi was effective in inducing remission and had an acceptable safety profile. The observed safety profile was as expected compared to clinical data results.

A Prospective Phase 2 Study of Venetoclax and Low Dose Ara-C (VALDAC) to Target Rising Molecular Measurable Residual Disease and Early Relapse in Acute Myeloid Leukemia

Introduction The 2021 European LeukemiaNet (ELN) recognizes MRD relapse as ≥1 log rise confirmed on repeat testing (Heuser Blood 2021). Molecular MRD relapse (e.g. NPM1mut) precedes clinical relapse by ~3-4 months (Ivey NEJM 2016) and provides a window of opportunity for pre-emptive therapy to be delivered prior to clinical relapse. Venetoclax (VEN)-based low intensity therapy is associated with rapid achievement of clinical response in older patients (pts) with AML (DiNardo NEJM 2020 and Wei Blood 2020) but only has modest activity in relapsed/refractory AML. We hypothesized that VEN-based therapy initiated at the time of MRD relapse could be associated with improved clinical response and longer clinical benefit. We therefore conducted a prospective study to explore the efficacy of low dose ara-C (LDAC) + VEN in pts with AML and MRD relapse (ACTRN12619000746134). Methods This multicenter phase 2 study stratified pts into either oligoblastic relapse (marrow blasts 5-15%; Group A), or molecular MRD relapse (Group B). Pts received VEN 600 mg (days 1-28, without dose ramp-up for Group B) and LDAC 20 mg/m2 sc (days 1-10). Primary objectives were morphologic or MRD response (≥1 log reduction) in groups A and B, respectively. Key secondary objectives were realization of allogeneic hematopoietic cell transplantation (HCT), relapse-free (RFS) and overall survival (OS). The study was approved by Alfred Health ethics committee (196/19). NPM1mut and other fusions (per 100 ABL1) from bone marrow were analyzed by RT-qPCR, and IDH1/2mut by Bio-RadTM droplet digital PCR. Results A total of 48 pts were recruited (median age 67; range 18-80). Cytogenetic risk was intermediate in 91%, favorable in 4.5% and adverse in 4.5%. Most (94%) had received prior intensive chemotherapy and only 2 (4%) had received prior HCT in first remission. The median interval from AML diagnosis to study entry was 13.7 months (IQR 9, 23). At the time of study screening, 22 (46%) pts had oligoblastic disease and 26 (54%) MRD relapse. Oligoblastic relapse included pts with early progression not captured by interval MRD surveillance. Pts received a median of 3 cycles (range 1-21+) of VEN-LDAC (ongoing in 11). Reasons for treatment cessation in 37 pts were: HCT (n=19, 51%), treatment failure (n=11, 30%), adverse events (n=3), donor lymphocyte infusion (DLI, n=2) or death before response assessment (n=2). One patient (Group B, NPM1mut) was deemed not evaluable for response assessment after only receiving 9 days of therapy but included in the survival analysis. Among 22 pts with oligoblastic disease, CR/CRi was achieved in 17 (77%). Two additional pts achieved morphologic leukemia-free state and 1 had stable disease. MRD response (≥1 log reduction) among those with an evaluable marker (N=8; all NPM1 mutated) was achieved in 8/8 (100%), with MRD negative in 6/8 (75%) (Figure). Among 25 evaluable pts with MRD relapse, MRD response (≥1 log reduction) was observed in 68% and MRD negative in 52%. Of patients with NPM1mut AML treated at MRD relapse, 13/19 (68%) achieved an MRD response and 10/19 (53%) an MRD negative response (Figure). An MRD response was observed in 2/3 with IDH1/2mut, 1/2 with core-binding factor and 1/1 with KMT2A::MLLT3. Bridging to HCT or DLI (median time 4 months) was successful in 18/27 (67%) pts ≤70 years. With a median follow up time of 14.4 months, the median RFS was 21.5 months and not reached for OS. The estimated 18-month RFS was 63.3% (95% CI, 48.0-83.5) and OS 71.1% (95% CI, 56.5-89.4). Similar outcomes were observed for Groups A and B. Subsequent HCT (as a time-dependent covariate) was the only significant factor for RFS (HR 0.13, 95% CI 0.03-0.61) but not OS (HR 0.48, 95% CI 0.13-1.75) in a multivariate Cox regression model that included age, features at original diagnosis (NPM1, FLT3-ITD and ELN 2017 risk), time since AML diagnosis, and study cohort (A vs B). FLT3-ITD was detected in 3/7 (43%) of relapsed pts. Conclusions In this prospective study of pts with early relapsing AML (oligoblastic or MRD relapse), VEN in combination with LDAC induced a high rate of molecular MRD response, resulting in excellent RFS and OS outcomes. Follow-up is ongoing to determine the durability of response. This novel MRD-targeting approach is being further investigated in a multi-arm, precision-based platform trial ( INTERCEPT: Investigating Novel Therapy to Target Early Relapse and Clonal Evolution as Pre-emptive Therapy in AML; ACTRN12621001265864). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

AB0551 TREATMENT WITH IXEKIZUMAB FOLLOWING SECUKINUMAB FAILURE IN PATIENTS WITH PSORIATIC ARTHRITIS: REAL-LIFE EXPERIENCE FROM A RESISTANT POPULATION

Background:Anti-IL17 agents, such as Secukinumab (SEC) and Ixekizumab (IXE) have been shown to be efficacious for the treatment of psoriasis and PsA12. In the field of psoriasis, there is growing evidence of a successful switching between the two anti-IL-17 agents in case of an insufficient response to one of the treatments3 There is no information on the efficacy of switching between anti IL17 agents in PsA.Objectives:To assess the clinical response to IXE in patients with PsA following SEC failure.Methods:A retrospective observational study was conducted in two rheumatology centers in Israel, including PsA patients with a history of treatment with SEC, further treated with IXE for a minimum of 3 months. Lack of efficacy, loss of efficacy, and side effects over time were reported as a reason for switching to another anti-IL17 agent. The mean difference between the beginning of the follow up period and the different follow up points (6 and 12 months) was tested using a one-sample t-test. Time until treatment failure was estimated using Kaplan–Meier curves, and compared using the log-rank test. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional-hazards model to test the association between each variable and the time to treatment failure.Results:The study included 23 PsA patients (11♀/12♂), mean age 58.7 years±13.4 SD. Most patients (n=20, 86%) received 2+ TNFi and 10 patients (43%) received both TNFi and ustekinumab. Median number of biologics prior to SEC was 3 (IQR 2-4). There was a significant improvement in TJC at 6 and 12 months (-2.16 [-4.0, -0.3]; p=0.025 and-1.69 [-3.09, -0.28]; p=0.022, respectively). SJC was significantly improved at 6 months but not at 12 months (-2.68 [-5.3, -0.04]; p= 0.046 and -1.50 [-4.25,1.25]; p=0.26, respectively). CDAI score was significantly improved at 6 months (-10.19, [-16.26, -4.1], p=0.002) and at 12 months (-9.29 [-14.8, -3.71], p=0.003) as was SDAI score (-10.13 [-16.4, -3.8], p=0.003 and -12.2 [-17.1, -7.2], p=0.0002). At six months, PASI50 was achieved by 81% (13 patients), PASI75 was achieved by 63% (10 patients), PASI90 was achieved by 50% (8 patients) and PASI100 by 31% (10 patients). At 12 months, PASI50 and PASI75 was achieved by 57% (8 patients), PASI90 was achieved by 43% (6 patients) and PASI100 by 21% (3 patients).Over time, of the 23 patients treated with IXE, 15 patients (65%) had experienced treatment failure, with a median treatment period of 8 months (IQR 6.5-13.5), of which 4 (17%) had primary treatment failure and 11 patients (48%) secondary treatment failure. Reasons for treatment cessation were: worsening psoriasis (4 patients (27%)), worsening peripheral arthritis (4 patients (27%)), both (7 patients (47%)), worsening of axial disease (2 patients (13%)) and adverse events (1 patient, 6%).Conclusion:patients after failure of multiple biologic treatments experienced significant response of peripheral arthritis and dermatologic disease on IXE after they had previously failed SEC. . However, in this refractory cohort of PsA, the effect was limited on time with 65% failure after a median time of 8 months.Within class switch from SEC to IXE is a plausible therapeutic option in PsA patients following secukinumab failure.

Correlation of immune-related adverse events with peripheral baseline immune markers and overall survival in patients with metastatic melanoma on ipilimumab and chemotherapy.

9561 Background: Very few predictive markers have been validated for immune-related adverse events (irAE), which are the number one reason for cessation of treatment and treatment-related deaths on checkpoint inhibitors. In a phase II trial of combined ipilimumab (ipi) with carboplatin/paclitaxel (C/P) (NCT01676649), we sought to determine baseline peripheral blood markers predictive of irAEs and to correlate these adverse with subsequent survival. Methods: Thirty patients with untreated unresectable/metastatic melanoma were treated with C (AUC = 6) and P (175mg/m2) every 3 weeks x 5 and Ipi (3mg/kg) every 3 weeks x 4. irAEs were graded according to the CTCAE v5.0. Median follow-up was 60 months. Baseline blood markers was assessed by a 37 multiplex cytokine-chemokine platform (Meso Scale Discovery) and multiparameter flow cytometry. Results: Grade 2 or higher irAE occurred in 11/30 of patients (4 colitis, 2 hepatitis, 2 hypophysitis, 3 rash). Median survival was 43.8 months in patients with irAE and 14.5 months for those without irAE (p = 0.001). Pts with irAE had lower baseline circulating levels of IL-6 (3.6 vs. 19.8 pg/mL, p = 0.049), TNF alpha (7.6 vs. 11.6 pg/mL, p = 0.003), CXCL9 (83.4 vs. 116.8 pg/mL, p = 0.042) and CCL3 (52.3 vs. 76.4 pg/mL, p = 0.012), but higher baseline circulating dendritic cells (DC) (4.9 vs. 2.9 % of total PBMC, p = 0.002) and a lower level of myeloid-derived suppressor cells (MDSC) (0.8 vs. 1.7 %, p = 0.049). There was no correlation between baseline B cell circulating numbers or differentiation and irAEs. Conclusions: Although results from previous studies of ipi monotherapy vary, our small study shows a highly significant correlation between irAEs and improved long term outcome for patients treated with ipi/C/P. Our exploratory analysis also identifies putative predictive immune and cytokine-chemokine markers of irAEs, which are associated with: 1) Antigen presentation dysregulation (high DC cells) and lack of adequate auto-immune suppression (low MDSC), as also seen in classic autoimmune diseases; and 2) A low inflammatory baseline signature (low TNF, IL-6, CCL3, CXCL9) consistent with possible immune exhaustion and reduced lymphocytic homeostatic fitness. Our combined markers depict a dysregulated immune landscape favorable to the expansion of self-reactive immune cells under CTLA-4 blockade. Our results are hypothesis generating and require further evaluation in a larger group of patients, including PD-1 treated cohorts. Clinical trial information: NCT01676649.

South-West of England's Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).

Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. We sought to characterize the population of patients prescribed antifibrotics and determine the drug tolerability of these medications in the Northern hub of the Southwest of England regional ILD network.Methods: A retrospective analysis of all patients treated with antifibrotics between August 2012 and July 2017 was undertaken. Baseline characteristics including patient demographics and pulmonary physiology, in addition to drug tolerability and reasons for treatment cessation were collated. Data were compared using unpaired student’s t-test, Chi-squared, Mann–Whitney rank sum or ANOVA as appropriate. Logistic regression analysis evaluated clinical characteristics associated with discontinuation of pirfenidone therapy. P < 0.05 was considered statistically significant.Findings: A total of 164 patients, all with consensus diagnoses of IPF, were identified. Of these, 70.1% (115/164) received pirfenidone as their initial therapy. Baseline age, gender and pulmonary physiology did not differ significantly between groups. Drug discontinuation occurred most commonly due to adverse drug reactions events (ADRs) for both pirfenidone [40.0% (46/115)] and nintedanib [16.3% (8/49)]. Anorexia, rash and gastrointestinal disturbance were reported most commonly as the reason for cessation of pirfenidone; anorexia, nausea and weight loss for nintedanib. Duration of therapy prior to discontinuation because of ADRs did not differ significantly between medication groups but patients with a baseline FVC < 65% predicted, had a significantly shorter duration of pirfenidone prior to discontinuation due to ADRs, compared to those with a FVC 65–80% predicted. Multivariate logistic regression did not identify any independent baseline characteristics that predicted discontinuation of pirfenidone therapy prior to 52 weeks.Implications: Idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib had comparable treatment emergent adverse event (TEAE) profiles in clinical practice to those reported in clinical trials. The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.

Pain management for laminitis in the horse

SummaryThe inability to control pain is the most common reason for cessation of treatment and euthanasia in cases of laminitis, yet pain also serves a unique protective function in these cases, particularly in the acute phase when lamellar integrity is weakened. Successful analgesia requires an understanding of the disease pathophysiology, the sources of pain in laminitis, methods of serial pain evaluation, and methods of analgesia including systemic and regional techniques. This review discusses the approach to analgesia including detail of traditional and novel analgesic medications and techniques with specific reference to the laminitis case.

Psoriatic arthritis treatment regimens, therapy duration and reasons for cessation in the biologics era: a multi-centre Australian study.

To describe the treatment regimens, duration of therapy and reasons for disease-modifying antirheumatic drug (DMARD) cessation in a large psoriatic arthritis (PsA) cohort. A retrospective non-interventional multi-centre study using Audit4 electronic medical records, with de-identified, routinely collected clinical data from rheumatology practices in the OPAL consortium (Optimising Patient outcomes in Australian rheumatoLogy) during November 2015. Baseline characteristics, type and duration of conventional and biologic DMARDs (cDMARD and bDMARD, respectively), disease activity (Disease Activity Score of 28 joints C-reactive protein [DAS28-CRP]), and reasons for treatment cessation were recorded. A total of 3422 rheumatologist-diagnosed PsA patients were included: 60% female, mean age 54 years and disease duration 10 years. Of patients with treatment recorded (n = 2948), 46% were on cDMARD monotherapy, 19% bDMARD monotherapy, 13% combination bDMARD and cDMARDs, 11% combination cDMARDs and 10% no DMARDs. Of those with DAS28-CRP results (n = 494), the highest mean DAS28-CRP was 3.32 on combination cDMARDs, and the lowest was 2.19 on bDMARD monotherapy. Median duration on cDMARD monotherapy was 33.5 months (n = 2232), on bDMARD monotherapy 110.1 months (n = 751), on combination bDMARD and cDMARDs 68.5 months (n = 559). The most common reasons for cessation of cDMARD monotherapy was adverse reactions (41%), for bDMARD monotherapy lack of efficacy (26%), and for combination bDMARD and cDMARDs treatment completed or no longer required (37%). Most PsA patients were prescribed DMARD therapies with a large proportion receiving cDMARDs. Patients on combination cDMARD therapies had the highest DAS28-CRP results. Adverse reactions were the most common reason for cessation of cDMARD monotherapy, whereas for bDMARD monotherapy it was lack of efficacy.

A home enteral nutrition (HEN); spanish registry of NADYA-SENPE group; for the year 2013.

To present the results of the Spanish home enteral nutrition (HEN) registry of the NADYA-SENPE group for the year 2013. From January 1st to December 31st 2013 data was recorded for the HEN registry and further descriptive and analytical analysis was done. In this period 3 223 patients (50.6% men) and a total of 3 272 episodes of HEN were registered in 33 Spanish hospitals. The rate of prevalence was of 67,11 patients/million habitants/ year 2013. A high percentage of patients (98,24%) were older than 14 years. Adult's mean age was 69,14 years (sd 17,64) and men were younger than women p-value <0,001. Children mean age was 2,38 years (sd 4,35). The most frequent indication for HEN was neurological disease for children (49,1%). and for adults (60,6%). Gastrostomy was the most used administration route for children (51%) while younger ones were fed with NGT (p-value 0,003) also older adults (48%) were fed with this type of tube (p-value <0,001). The most frequent reasons for cessation of treatment was death, 44,4% were children and 54,7% were adults. The number of patients and hospitals registered increased in the last years while the other variables maintain steady. The registry developed allowing contrasted analysis of data in order to get more information.

Russian

The article features literature data for treatment of patients with HIV infections as well as factors for prescription the antiretroviral drugs. The analysis of the VAART use between 1012-13 in Karaganda region was conducted. The data of in-and outpatients with HIV infections are presented. The reasons for treatment cessation and the data of ARV of HIV patients‘ tuberculosis are shown.

AB1024 Side effects associated with the use of zolendronic acid

BackgroundThe zolendronic acid (ZO) is indicated in the treatment of osteoporosis and Paget’s disease, as well as in the prevention of fractures. The adverse effect (AE) more prevalent is the...

Treatment of Severe Atopic Dermatitis with Cyclosporine: A Review of Eight Patients

AbstractAtopic dermatitis is most frequently well controlled with topical therapeutic agents, but based on several studies, 10-20% of patients need systemic therapy. The most common systemic treatment for atopic dermatitis in everyday practice includes systemic corticosteroids, although there are insufficient valid data to support this. Cyclosporine is the treatment of choice for severe atopic dermatitis resistant to other commonly used treatment options, since its favorable therapeutic risk/benefit ratio is well documented in randomized placebo controlled trials, and also in uncontrolled trials. However, approximately 10% of patients with atopic dermatitis with indication for cyclosporine treatment are actually treated with this modality in Serbia, and there are no published case series on its use in this region so far. In this article, we evaluated the treatment efficacy and safety of cyclosporine microemulsion in patients with severe atopic dermatitis hospitalized at the Military Medical Academy in Belgrade from 2009 to 2012. This restrospective analysis included patients with severe forms of atopic dermatitis treated at the Department of Dermatology of the Military Medical Academy from 2009 - 2012. The hospital database was used to retrieve patients’ medical records. Approximately 200 patients were treated for atopic dermatitis and 20 patients were admitted to the hospital, 17 due to severe forms of disease. In total, 8 of 17 (47.05%) hospitalized patients with severe forms or erythroderma due to atopic dermatitis were treated with cyclosporine microemulsion with an initial dose of 4-5 mg/kg. Laboratory tests were done before treatment, 7 days later, and/or at the end of hospitalization. Therapeutic efficacy was evaluated based on the percentage of reduction of skin lesions from baseline to the end of hospital treatment (early efficacy), and at the end of follow-up (late efficacy). Duration of therapy, adverse events, treatment efficacy and reasons for treatment cessation were recorded during the follow-up period. There were five male and 3 female patients, with an average age of 36.8 years (15 - 60 years). Previous treatment modalities in all patients included emollients, topical and systemic corticosteroids and PUVA therapy. The average dose of cyclosporine was 4.5±0,5 mg/kg. Median reduction of skin lesions at discharge was 60%. There was no need for further hospitalization after an average of 10±3.2 days. Mean duration of treatment was 16 months (3 - 24), with an average reduction of skin lesions of 75% during follow-up. Arterial blood pressure increased in 3/8 (37.5%) patients, regardless of their age, with and average increase of systolic blood pressure of 11.9±11.6 mm Hg (median 7.5, 0-30 mm Hg) and diastolic blood pressure of 5.6±12.9 mm Hg (median 0, -10-20). Mean increase in urea concentration was 0.3 mmol/L (11.8%) and creatinine increased only in three patients by 4.2% (median increase 4 mmol/L). Hypertension was found in three patients during follow-up, and there were no other adverse events. In conclusion, based on previous studies and this small case series of hospitalized patients with severe forms of atopic dermatitis including erythroderma, cyclosporine can be regarded as a safe and effective treatment modality and it can be recommended as first line therapy in severe forms of atopic dermatitis refractory to topical therapy and phototherapy. Long term therapy, however, should be avoided and a maximum 1-2 year therapy is recommended.

The Safety and Tolerability of Oral Fludarabine, ±oral Cyclophosphamide and Iv Rituximab Therapy In Previously Untreated Patients with Chronic Lymphocytic Leukaemia (CLL) Aged ≥65 Years – Interim Analysis From the Australasian Leukaemia and Lymphoma Group (ALLG) and CLL Australian Research Consortium (CLLARC) CLL5 Study.

AbstractAbstract 699 Background:Combination immunochemotherapy with fludarabine (F), cyclophosphamide (C) and rituximab (R) gave superior progression free and overall survival compared to FC in the German CLL8 Study. The median age in CLL8 was 61 years compared to a median age for overall CLL patients of 72 years. There is ongoing debate regarding the tolerability and safety of FCR in elderly patients. Arbitrary dose reductions are common practice. Oral FC is more convenient for many older patients. Methods:Previously untreated patients with progressive CLL aged ≥65 were randomised to one of three treatment regimens FR5, FCR3 and FCR5 as follows: (i) F 24mg/m2 po D1-5 + R (375 mg/m2 C1, 500mg/m2 C2-6) iv D1 (FR5), (ii) F 24mg/m2 po and C 150mg/m2 po D1-3 + R iv D1 (FCR3) or (iii) F 24mg/m2 po + C 150mg/m2 po D1-5 + R iv D1 (FCR5), all given at monthly intervals for an intended 6 cycles. The dosage of FCR5 is equivalent to standard intravenous FCR in the CLL8 Study. Patients were administered their therapy arm with no dose reduction. Fludarabine dosing was reduced according to renal function by calculated GFR. Therapy was delayed by 2 weeks if there was any grade 3 or 4 toxicity. If this was unresolved after 2 weeks, patients were taken off study. If toxicity resolved to grade 2 or less, therapy proceeded. Results:Over half the planned patients (65 of 120) were recruited by 1 August, 2010 from 21 centres in Australia and New Zealand with the study having been open for 18 months. Median age is 72 (range 65–85) years. Binet stage at registration was progressive A – 11 (16.9%), B – 32 (49.2%) and C – 22 (33.8%). Randomisations are FR5 – 22, FCR3 – 22 and FCR5 – 21. FISH data is available on 50 patients: 25 with 13q-, 9 with 12+, 4 with 11q−, and 6 with 17p−. P53 functional analysis is available on 15 patients. Interim reasons for cessation of treatment, dose delay and clinical responses are shown in tables 1, 2 and 3 respectively for the total patient cohort. Cessations for reasons other than toxicity occurred in 7 patients: intercurrent illness (N=2) with acute myocardial infarction (AMI) and recurrent episodes of amnesia, and other reasons (N=5). Deaths were recorded for 2 patients due to infection and AMI.Table 1Reason for cessation of treatmentFrequencyPercentCompletion of protocol treatment1346.4%Unresolved Grade 3/4 toxicity >2 weeks828.6%Intercurrent illness27.1%Other517.9%Total28100.0%Table 2Dose delays during treatmentFrequencyPercentYes3061.2%No1938.8%Total49100.0%Table 3Reponses in patients who have completed treatmentInterim staging after 3 cyclesInitial clinical response after 6 cyclesFinal staging 2 months after completionComplete Remission131911Nodular Partial Remission115Partial Remission27910Stable Disease232Progressive Disease000Total433228 Conclusions:Oral F(C)R therapy appears generally safe and well tolerated to date in CLL patients aged ≥65 years requiring first-line treatment. Using stringent stopping criteria with delay of 2 weeks for recovery of grade 3 or 4 toxicity but no dose reduction, about half the patients will stop early due to toxicity or intercurrent illness. Nevertheless, response rates are high. Accrual is ongoing. Disclosures:Mulligan:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Schering, now Genzyme: Honoraria. Seymour:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Patterns of treatment in Australian men following fracture

This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50years and older who had sustained fracture in the study period. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.

Long-term adherence to antihypertensive therapy: a survey in four primary care clinics

Background: Many hypertensive patients have suboptimal control of their blood pressure. One of the most common causes is poor adherence with treatment. Aim: To identify factors associated with poorer adherence to antihypertensive treatment. Methods: The study was conducted in four urban clinics of Clalit Health Services (Israel's largest Health management organization): 3799 patients aged > 20 years with hypertension in whom a new antihypertensive medicine was started in a 3-year period were included. Data included: age; gender; chronic diseases; type of antihypertensive medicine; and adherence with treatment. Reasons for non-adherence had been evaluated in a random sample of 453 of the medical records. Results: Of the patients, 2234/3799 (58.8%) stopped ≥ 1 medicine. Lower adherence was associated with female gender, new immigration, ischemic heart disease and being a non-diabetic. Adherence was related to the type of medicine. The highest rates of adherence were found with the use of angiotensin receptor blockers (59.1%) and selective β-blockers (59%), and the lowest with non-selective β-blockers (30.1%). There was no documentation of the reason to medicine cessation in 183/453 (40.4%) of the medical records. In 20.1% of cessations, the physician continued to prescribe the drug, despite the fact that the patient had stopped purchasing it. Common reasons for treatment cessation were side effects (15%) and lack of blood pressure control (5.5%). Conclusions: Adherence with antihypertensive treatment declines with time and is associated with the type of medicine, and sociodemographic and clinical backgrounds. Family physicians must increase their documentation and awareness to medicine adherence.

Long-Term GH Therapy: Epidemiology and Auxologic Outcome

Objectives: Epidemiologic and auxologic characteristics of patients treated with GH during childhood and adolescence and entered in a national registry in Catalonia were studied between 1988 and 1997. At the end of 1997, prevalence was 53.2 treatments/100,000 inhabitants aged 0–14 years. Maximum annual incidence rates were observed in 1990 and 1991 (34.0–35.6 cases/100,000 inhabitants aged 0–14 years). Study Design: Analysis of treatments terminated in 1993 (n = 548) revealed, for the three principal reasons for cessation of treatment (‘near-final height’, ‘adequate height but further growth potential’, and ‘poor growth response’), that males began and ended treatment at older ages with a better auxologic situation in SDS than girls at the beginning and end of therapy in the first two subgroups, with a similar duration of therapy. Severe GH deficiency (GHD) [both multiple pituitary hormone deficiency (MPHD) and the most severe isolated GHD (IGHD-A)] was more frequent in the group ending treatment at ‘near-final height’, whereas cessation of therapy because of ‘poor growth response’ was more frequent in the group with ‘other causes of short stature’ and no demonstrable GHD by routine tests. In the near-final height group, after excluding Turner’s syndrome, MPHD and GHD cases secondary to brain tumors and GH deficiencies associated with malformative syndromes, positive linear correlations were observed between HSDS at the end of treatment and HSDS at the beginning, predicted adult height SDS (PAHSDS) and target height SDS (THSDS). Multiple regression analysis showed that in this group of patients, 41.4% of the variability in HSDS increment can be explained by the equation: HSDS increment = –0.33 + 0.29 THSDS – 0.68 HSDS at the beginning of treatment. Results: The outcome showed a reasonable use of GH, since good-response cases generally continued treatment until final height whereas therapy was suspended in doubtful cases.

Nocturnal Nasal Ventilation for Treatment of Patients With Hypercapnic Respiratory Failure

We reviewed the Mayo Clinic experience with nocturnal nasal ventilation (NNV) and retrospectively assessed the clinical benefits, patient compliance, and complications. NNV had been instituted in 26 patients with daytime hypercapnia and nocturnal hypoventilation due to neuromuscular diseases or chronic obstructive pulmonary disease. After initiation of NNV, 21 of 26 patients continued to use this treatment regularly (81% compliance rate) and considered their life-style improved. In this subset of patients, the arterial partial pressure of carbon dioxide during unassisted breathing decreased from 64 +/- 13 to 51 +/- 7 mm Hg, and the arterial partial pressure of oxygen increased from 58 +/- 12 to 68 +/- 8 mm Hg. No significant change was noted in the forced vital capacity or maximal respiratory pressures. Four of the five patients in whom NNV had been discontinued cited discomfort related to the mask or severity and poor prognosis of the underlying illness as reasons for cessation of treatment. We conclude that NNV is well tolerated by most patients and may improve alveolar ventilation and arterial oxygenation in patients with chronic respiratory failure.

An evaluation of the duration and the results of orthodontic treatment.

abstract – In 1,486 schoolchildren with various anomalies, different needs of orthodontic treatment, and treated with different techniques, the following variables were studied: uncompleted orthodontic treatment and reason for cessation of treatment, duration of active treatment, duration of retention period, complete registration period, results of treatment. One to five years after the end of treatment, 300 cases were examined regarding relapse, opinion of treatment, and opinion of the results of treatment.