Long-term Maintenance Of Remission Research Articles

Adapting dose-response methodology to improve clinical trial design for psychotherapies.

Conventional randomized controlled trials (RCTs) have long served as the foundation of research in clinical psychology; however, most treatments for eating disorders show only modest effects on reduction of symptoms and maintenance of long-term remission. New options for psychotherapy treatment development research, beyond continuing to pursue additive or subpopulation approaches, are needed. One option is to apply dose-response designs, which are commonplace in studies of pharmacology, toxicology, and medical research, and characterized by the evaluation of the amount of exposure (dose) to an intervention, and the resulting changes in body function or health (response). Eating disorder interventions are particularly well-suited for dose-response treatment designs. The deadly nature of eating disorders makes it imperative that patients are not turned away for not being "ready" to engage with treatment. By identifying optimal doses, research will likely yield a more parsimonious course of treatment, which will lend itself to reduced costs, greater uptake, and reduced drop-out. Limited use of within-subject designs in trials for patients with eating disorders has produced fast-track efficacy studies and omitted key elements in the treatment development pathway. To decrease reliance on RCT's, dose-response methods should be applied as an alternative study design. Eating disorders are associated with medical and psychiatric comorbidities, poor quality of life, and high mortality. Access to evidence-based services for patients with eating disorders is limited, and identifying additional effective treatment options can be difficult because of challenges inherent to randomized-controlled trials. This manuscript describes an alternative trial methodology to maximize the information that can be gathered prior to utilizing a standard large-scale efficacy design.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

CD19 CAR-T Cell Therapy in Children with Relapsed and Refractory B-ALL

IntroductionCD19 CAR-T is a highly effective therapy among children with relapsed/refractory B-ALL. The optimal approach to delivery of this therapy and the best post-remission strategy remain to be established. We have tested in a prospective academic trial CD19 CAR-T cells manufactured at the point-of-care based on the automatic bioreactor platform. Based on the results of the first part of the trial, a toxicity mitigation strategy with conditional split dosing and refined post-remission therapy based on allogeneic HSCT was implemented. We report here the results of toxicity mitigation strategy approach as well as the long-term outcome with regard to the HSCT consolidation.Patients and methodsA total of 57 pts with relapsed/refractory B-ALL were screened, 54 pts were included in the trial, and additional 3 pts were eligible for compassionate use of CD19 CAR-T cell therapy. The CliniMACS Prodigy T-cell transduction process with lentiviral second generation CD19.4-1BB zeta vector (Lentigen, Miltenyi Biotec) was used for CAR-T manufacturing. All patients received prophylactic tocilizumab before CAR-T cells infusion.In the first part of trial 33 pts received lymphodepleting chemotherapy containing cyclophosphamide (750 mg/m2) and fludarabine (120 mg/m2), CAR-T cells was administered in dose-escalating regimen (0.1, 0.5, 1, and 3х10 6/kg b.w.).After the interim analysis, treatment scheme was modified to adapt the lymphodepletion therapy and the starting CAR-T dose to the leukemia burden. Twenty-four consecutive pts were divided into “low leukemia burden” (n=10) and “highleukemia burden” (n=14) groups, based on the threshold of 15% leukemic cells in the bone marrow.Patients with low leukemia burden received the same lymphodepletion chemotherapy as in the first part of the trial, and a single fixed dose of CAR-T cells at 1x10 6/kg b.w.Patients with high leukemia burden received an escalated lymphodepletion (fludarabine 120 mg/m 2, cyclophosphamide 750 mg/m 2, cytarabine 900 mg/m 2, etoposide 450 mg/m 2, dexamethasone 30 mg/m 2) and a divided dose of CAR-T. Day 0 CAR-T dose was set at 0.1 x10 6/kg. The second dose of 0.9x10 6/kg b.w. was administered between day 7 and day 14 if the following criteria were met: bone marrow leukemia burden by flow cytometry < 15% and CRS and/or ICANS grade within 3 previous days does not exceed grade 2.ResultsThirty patients included in the first part of the trial, were evaluable for response at day 28, and 27 (90%) of them had MRD-negative remission. Interim analysis showed that grade 3-5 CRS and neurotoxicity were associated exclusively with large leukemia burden (>15% blasts in the bone marrow) at the enrollment (p=0,003).With the risk-adapted strategy (part 2 of the trial), 8 patients (80%) with low leukemic burden achieved CR at day 28, and all patients (100%) with high leukemic burden achieved complete remission on day 28. In the high burden cohort 4 patients received the second CAR-T infusion, while the remaining 10 patients did not receive second dose due to either toxicity grade ³2 (4 pts), or persistence of >15% blast cells in bone marrow (6 pts). There were no cases of grade IV-V toxicity among patients with high leukemia burden, Table 1.For all patients the median follow-up for survivors was 490 days (287-1193), the cumulative incidence of relapse after initial response was 69.6%, median time to relapse was 250 days (58-696). HSCT during the CR was performed in 15 patients. The median time between first CAR-T infusion and HSCT was 96 days (41-292). Three patients (20%) relapsed early after HSCT (88, 114 and 155 days). Event-free and overall survival for the total cohort was 19.6% and 56.4%, respectively. Among the 34 pts, who did not receive HSCT in CR after CAR-T therapy, EFS and OS were 14.7% and 55.7%. Among the 15 pts, who received HSCT as consolidation, EFS and OS were 86.1% and 80%, p-value for HSCT vs no HSCT 0.125 (OS) and 0.0001 (EFS).ConclusionLow doses of non-cryopreserved CAR-T cells (0.1*10 6/kg), manufactured at the point-of-care, demonstrated high efficacy in patients with high initial leukemia burden, as well as favorable profile of life-threatening toxicity. The proposed risk-adapted strategy of CAR-T dosing allows to achieve high remission rate in all patients (with high and low leukemic mass). HSCT is likely to be a necessary modality for consolidation and long-term maintenance of remission after CAR-T therapy among a majority of patients with advanced B-ALL. [Display omitted] DisclosuresMaschan: Miltenyi Biotec: Speakers Bureau.

Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis

BackgroundWe previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy.MethodsThe relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study).ResultsIn the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA 6 months after the initiation of remission-induction therapy than in patients in remission. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months.ConclusionWe herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.

Management of Ulcerative Colitis: Putting Patients at the Centre

The treatment landscape of ulcerative colitis (UC) is changing, with new treatment options becoming available and insights into disease management demonstrating the importance of a patient-centric approach. Induction and maintenance of long-term remission are important treatment goals. However, some of the current treatment options often have limited efficacy, which may be coupled with an unfavourable safety profile, such as an increased risk of infection. A multiphase approach to disease management, which includes induction and maintenance of remission through close monitoring, is a viable clinical strategy. Selecting an appropriate first-line therapy is a crucial part of this strategy, as options are sometimes limited for patients who have failed anti-tumour necrosis factor (TNF) therapy. The integrin antagonist, vedolizumab, has demonstrated effective induction and maintenance of clinical remission in both anti-TNF-naïve and anti-TNF-failure patients, with no increase in infection risks. Therefore, vedolizumab should be considered for inducing and maintaining remission as part of a patient-centric disease management programme. The development of simplified monitoring systems that provide an indication of endoscopic activity will also aid patients in taking charge of their disease management. In conclusion, putting our patients at the centre of a proactive model of disease management can help prevent complications in the long-term, and selecting suitable first-line therapies is an important step in this process.

Efficacy and tolerability of certolizumab pegol in Crohn's disease in clinical practice.

To assess the efficacy and tolerance of certolizumab pegol (CP) in patients with Crohn's disease (CD) treated in the Department of inflammatory bowel diseases of the A.S. Loginov Moscow Clinical Research Center and to determine the predictors of response to therapy. All patients with CD who had received the treatment of CP were observed prospectively for at least 6 months or until the date of discontinuation of the drug. The effectiveness of the study was assessed response to therapy by the 6th week, maintaining the clinical response (6th and 26th weeks), the dynamics of endoscopic parameters by the 10th and 54th week of therapy, long-term maintenance of remission, healing fistula. Used univariant and multivariate analyses of predictors of response to treatment. The study included 39 patients: 12 (30.7%) men and 27 (69.3%) female, the average duration of observation was 104 weeks. The interdepartmental range was in the range from 28 to 158 weeks. Clinical improvement occurred in 38 out of 39 (97.4 %) patients with CD. Comparative analysis of response to treatment with CP have bionaive patients previously treated with another inhibitor of TNF-α. In the group of bionaive response to therapy in a month, 6 months and at the end of the observation period occurred at 100.0%, 95.0% and 95.0%, respectively. In the group of patients previously treated with GSI, the response rate was about 94.4 %, 88.9 % and 77.7% week 54 endoscopic response and endoscopic remission was maintained in 46,2% and 30,1% patients, complete healing of the mucosa on the background of maintenance therapy, CP, was preserved in 20.5% of patients with Crohn's disease. In the group of patients with perianal lesions (n=13) complete closure of all fistulas was observed in 5 (38.6 %) patients, partial response was observed in 4 patients (30,7%) patients, in 4 (30.7 %) closure of fistulas occurred. The frequency of adverse events was 0 cases (0.0%). The dose escalation was required in 3 patients (7,7%) patients with CD. Dose escalation in our study required patients with high initial CDAI and previous inefficiencies of the other two inhibitors of TNF-α. Reliable predictors of secondary loss of response and need for dose escalation of the drug has been the continued level of CRP &gt;5 mg/l after 2 weeks initiation of therapy CP and smoking. The obtained results demonstrate the efficacy and tolerability profile of CP appropriate for long-term CD therapy in real clinical practice.

Maintenance Treatment Of Eosinophilic Esophagitis With Swallowed Topical Steroids Alters Disease Course Over A 5-Year Follow-up Period In Adult Patients

Although swallowed topical corticosteroids (STCs) are effective in inducing remission of active eosinophilic esophagitis (EoE), there are few data on maintenance of long-term remission. We evaluated the long-term effectiveness of STC therapy for adults with EoE. We performed a retrospective study using the Swiss EoE database. We analyzed data on 229 patients with EoE treated with STCs (175 male; mean age at diagnosis, 39±15 years; median time until diagnosis, 6 years) from 2000 through 2014. Patients were followed for a median of 5years (interquartile range [IQR], 3-7 years). We collected data from 819 follow-up visits on clinical, endoscopic and histological disease characteristics. The primary endpoint was proportions of clinical, endoscopic, and histological remission in all patients and groups, based on the status and duration of STC treatment. Patients were taking STCs at 336 of the follow-up visits (41.0% of visits). The median duration of STC use before a follow-up visit was 347 days (IQR, 90-750 days) corresponding to 677 doses (IQR, 280-1413 doses) of 0.25 mg each. At the visits, higher proportions of patients who were still taking STCs were in clinical remission (31.0%) compared to patients not taking STCs (4.5%) (P <.001), as well as endoscopic remission (48.8% vs 17.8%; P < .001), histologic remission (44.8% vs 10.1%; P < .001), and complete remission (16.1% vs 1.3%; P < .001). Higher cumulative doses of STCs and longer durations of treatment were associated with higher proportions of clinical and complete remission. No dysplasia or mucosal atrophy was detected. Esophageal candidiasis was observed at 2.7% of visits in patients taking STCs. In an analysis of data from the Swiss EoE database, we found maintenance therapy with STCs to achieve complete remission at 16.1% of follow-up visits, which was higher than in patients receiving no treatment (1.3%). Given the good safety profile of low-dose STC, we advocate for a prolonged treatment. Dose-finding trials are needed to achieve higher remission rates.

Other Antidepressants.

Other Antidepressants.

MON-P270: A Meta-Analysis of the Effectiveness of Daily Enteral Nutrition in the Maintenance of Long Term Remission in Crohn’s Disease

MON-P270: A Meta-Analysis of the Effectiveness of Daily Enteral Nutrition in the Maintenance of Long Term Remission in Crohn’s Disease

Chronic Inhibition of Complement C1s By TNT009 Produces Sustained, Complete Remission in Patients with Severe, Transfusion-Dependent Cold Agglutinin Disease (CAD)

Background: We recently presented that the humanized anti-complement C1s monoclonal antibody, TNT009, rapidly stoppedhemolysisand correctedanemiain patients with severe CAD in an ongoing Phase 1b clinical trial. After completion of washout from protocol treatment, these patients suffered relapse of CAD with a drop inhemoglobinto pre-dose levels. We now report on the clinical experience of their extended re-treatment under the Named Patient provision of the Austrian Drug Act, which provided the occasion: 1) to explore lower dose regimens and alternative dosing schedules; 2) to try to recapitulate the initial success of complete remission under protocol treatment; 3) to test the durability of response with a longer term maintenance treatment with TNT009.Methods: In order to test a lower dose regimen of TNT009, the Phase 1b trial dosing of 60 mg/kg IV once weekly for both loading and maintenance was reduced to 45 mg/kg IV once weekly (4x) followed by maintenance with 45 mg/kg every other week. A simplified dosing regimen was then tried, using a single priming dose of 60 mg/kg on Day 0 followed by 60 mg/kg every other week (biweekly) thereafter beginning on Day 7. This TNT009 biweekly maintenance with 60 mg/kg was continued indefinitely to test the durability of the effect, to monitor for safety, and to serially assess their hematologic response to TNT009.Results:All infusions were well tolerated without premedication and without relevant adverse effects. TNT009 re-exposure immediately decreased CH50 activity and increased complement C4 levels, confirming the rapid onset ofpharmacodynamiceffect. The concordant and sustained effect of TNT009 on hematologic parameters related tohemolysisandanemiasis illustrated in the composite Figure 1 for the first patient treated, C1001. This patient has undergone three treatment episodes with TNT009: weekly dosing at 60 mg/kg under the Phase 1b protocol (left); weekly → biweekly 45 mg/kg (center); 60 mg/kg on Day 0 and biweekly thereafter starting on Day 7 (right). Note that the CH50 serves as apharmacodynamicmarker for the effective inhibition of the classical complement pathway by TNT009. Each new episode of treatment with TNT009 induced remission ofhemolyticanemia, and relapse occurred following washout (60 mg/kg weekly x 4) orpharmacodynamicbreakthrough (45 mg/kg maintenance regimen). Although it appears that the reduced dose maintenance regimen of 45 mg/kg biweekly does not suffice to maintain full C1s inhibition, there is no evidence oftachyphylaxisas restoration of full dose treatment at 60 mg/kg biweekly was able to restore remission again.A similar pattern of results was observed in the other patients offered Named Patient treatment with TNT009, but with two instructive exceptions. Patient C1004 had unsuspected erythropoietin deficiency and did not achieve complete normalization ofhemoglobinuntil concomitant treatment with erythropoietin was begun. Patient C1003 did not have CAD but Cold Agglutinin Syndrome (CAS) secondary to an extensivelymphoplasmacyticlymphoma (LPL). Initially she was treated with TNT009 monotherapy and did not respond. TNT009 was then stopped and her LPL was treated withibrutinib, resulting in a gradual amelioration of heranemiauntil anintercurrentinfection triggered relapse of herhemolyticanemia. At that time re-treatment with TNT009 (whileibrutinibwas continued) quickly normalized her hematologic parameters. Eventually TNT009 was able to increasehemoglobinlevels to >12 g/dLin all 5 of 5 treated patients.Conclusion:TNT009 was previously shown to induce rapid correction ofhemolyticanemiain severe CAD patients in a Phase 1b trial. It has now been shown that subsequent washout of TNT009 leads to relapse in all patients, and that re-induction of remission by TNT009 is possible in all. Long-term maintenance of remission can be achieved by dosing TNT009 at 60 mg/kg biweekly, the dose regimen to be tested in larger-scale clinical trials of CAD. [Display omitted] DisclosuresGilbert:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Panicker:Truenorth Therapeutics, Inc.: Employment. Parry:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Jaeger:Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses.

Detailed profiling of anti-desmoglein autoantibodies identifies anti-Dsg1 reactivity as a key driver of disease activity and clinical expression in pemphigus vulgaris

With their near-universal presence in patients and ease of clinical measurement, anti-desmoglein (Dsg) antibodies serve as primary candidates for creating prognostic tools in Pemphigus vulgaris (PV). Although the desmoglein compensation hypothesis postulates a clear relationship between anti-Dsg autoantibodies and clinical phenotype in PV, recent studies have questioned the fidelity of this hypothesis as a predictor of lesion morphology. Moreover, few studies address the association of anti-Dsg antibodies to other clinical parameters such as disease phase and age at onset. Using the largest patient repository to date in PV, we present a detailed analysis of anti-desmoglein antibody profiles across a comprehensive range of dynamic (disease phase, therapy, lesion morphology) and temporal (disease duration, age at sampling, age at onset) clinical parameters. Our data highlight the non-traditional but key role of anti-Dsg1 levels in tracking disease activity. We show that declining anti-Dsg1 levels may predict progression from active phase to early remission and long-term maintenance of remission, regardless of lesion morphology. In contrast, many remittent patients have elevated levels of anti-Dsg3 without lesional activity. Furthermore, we describe a unique subset of remittent patients that develop chronic transient lesions (lasting <1 week) in the setting of elevated anti-Dsg3 levels but do not meet the consensus criteria for active phase. Re-classification of patients with transient lesions as “active” may shed new light on pathophysiological processes underlying cycles of blister formation and rapid spontaneous healing in PV. Additionally, we provide evidence for the potential attenuation of the immune response with prolonged disease duration. Our data fit into the broader effort of immunoprofiling to promote data-informed decision-making regarding diagnosis, prognosis and treatment of complex diseases.

Hepatic encephalopathy

Hepatic encephalopathy causes significant cognitive impairment and morbidity in patients with cirrhosis; however, hepatic encephalopathy is considered a reversible syndrome once recognized clinically. Although hepatic encephalopathy is not a single clinical entity, the pathophysiology resulting in brain dysfunction is not fully understood, although it is believed that ammonia production is an important contributing factor. The purpose of this review is to highlight studies used to test for hepatic encephalopathy and those utilizing specific new treatments. A 'STROOP' smartphone app has been developed to allow clinicians to test for covert hepatic encephalopathy (CHE). Lactulose therapy was effective for cirrhotic patients as primary prophylaxis to prevent overt hepatic encephalopathy (OHE) episodes. In patients without prior OHE, probiotics can be useful in preventing OHE. Lactulose, probiotics, L-ornithine-L-aspartate, and potassium-iron-phosphate-citrate have been studied in the treatment of CHE. Rifaximin was found to be safe and well tolerated in long-term maintenance of remission from OHE; however, compared to lactulose therapy in CHE, it is not cost-effective. Refinement in clinical management strategies for patients with cirrhosis and hepatic encephalopathy appears to continue to contribute to improved patient outcomes.

Tumor Necrosis Factor Alpha Blocking Agents as Treatment for Ulcerative Colitis Intolerant or Refractory to Conventional Medical Therapy: A Meta-Analysis

BackgroundEfficacy of tumor necrosis factor alpha (TNF-α) blockers for treatment of ulcerative colitis that is unresponsive to conventional therapy is unclear due to recent studies yielding conflicting results.AimTo assess the efficacy and safety of anti-TNF-α agents for treatment of ulcerative colitis patients who were intolerant or refractory to conventional medical therapy.MethodsPubmed, Embase, and the Cochrane database were searched. Analysis was performed on randomized controlled trials that assessed anti-TNF-α therapy on ulcerative colitis patients that had previously failed therapy with corticosteroids and/or immunosuppressants. The primary outcome focused on was the frequency of patients that achieved clinical remission. Further trial outcomes of interest included rates of remission without patient use of corticosteroids during the trial, extent of mucosal healing, and the number of cases that resulted in colectomy and serious side effects.ResultsEight trials from seven studies (n = 2122) met the inclusion criteria and were thus included during analysis. TNF-α blockers demonstrated clinical benefit as compared to placebo control as evidenced by an increased frequency of clinical remission (p<0.00001), steroid-free remission (p = 0.01), endoscopic remission (p<0.00001) and a decrease in frequency of colectomy (p = 0.03). No difference was found concerning serious side effects (p = 0.05). Three small trials (n = 57) comparing infliximab to corticosteroid treatment, showed no difference in frequency of clinical remission (p = 0.93), mucosal healing (p = 0.80), and requirement for a colectomy (p = 0.49). One trial compared infliximab to cyclosporine (n = 115), wherein no difference was found in terms of mucosal healing (p = 0.85), colectomy frequency (p = 0.60) and serious side effects (p = 0.23).ConclusionTNF-α blockers are effective and safe therapies for the induction and maintenance of long-term remission and prevention of treatment by colectomy for patients with refractory ulcerative colitis where conventional treatment was previously ineffective. Furthermore, infliximab and cyclosporine were found to be comparable for treating acute severe steroid-refractory ulcerative colitis.

The interactive effects of effort to regulate alcohol use, anxiety disorders and affective disorders on long-term remission from alcohol dependence

Objective: This study examined how effort to regulate alcohol use may interact with anxiety and affective disorders to influence long-term remission from alcohol dependence.Method: Using participants (n = 96; 73% male; 66% children of alcoholics; 71% non-Hispanic Caucasian; 26% Hispanic) from a high-risk community study who showed evidence of recovered alcohol dependence at baseline, this study examined whether effort to regulate alcohol use at the baseline assessment significantly influenced the likelihood of maintaining remission from alcohol dependence for a period of five years or more. This study also examined whether having an anxiety or affective disorder interacted with effort to regulate alcohol use. All analyses controlled for treatment history, baseline alcohol use, parent alcoholism, age and gender.Results: Results from logistic regressions showed that effort to regulate alcohol use had a significant unique main effect on long-term maintenance of remission from alcohol dependence. Having an affective and/or anxiety disorder did not have a significant main effect on the maintenance of remission. However, having an anxiety/affective disorder significantly moderated the influence of effort to regulate alcohol use such that the protective effect of effort to regulate use on remission from alcohol dependence was only significant for those without an affective or anxiety disorder.Conclusions: Individuals who try harder to limit their drinking are more likely to maintain long-term remission from alcohol dependence. However, affective and anxiety disorders may undermine the protective effect of effort to regulate alcohol use on long-term remission.

Long-term Maintenance of Remission with No Dose Escalation After Re-induction with Certolizumab Pegol in Patients with Crohnʼs Disease Exacerbation Who Were Naïve to Anti-TNF Treatment: 4-Year Results from the PRECiSE 4 Study

Long-term Maintenance of Remission with No Dose Escalation After Re-induction with Certolizumab Pegol in Patients with Crohnʼs Disease Exacerbation Who Were Naïve to Anti-TNF Treatment: 4-Year Results from the PRECiSE 4 Study

Long-term maintenance of remission with no dose escalation after re-induction with certolizumab pegol in patients with Crohnʼs disease exacerbation: 3-year results from the PRECiSE 4 study

Long-term data on therapeutic strategies that aim to recapture patients with relapsed Crohn's disease (CD) are lacking. Here we report the long-term (3-year) efficacy and safety of certolizumab pegol (CZP) in patients who, after initial response to CZP induction, experienced disease exacerbation on either active or placebo maintenance therapy in PRECiSE 2 (P2). Patients were re-induced with CZP, or in the case of those on active treatment given 1 single extra dose, and then continued with q4w maintenance therapy in PRECiSE 4 (P4). In the P2 study, 428 patientswhoresponded to induction therapy with CZP at Week 6 were randomized to continuous therapy with CZP or placebo (drug interruption) during weeks 6-26. Patients who had an exacerbation of symptoms before Week 26 could enter P4, an open-label extension study. In P4, patients received CZP 400 mg at Weeks 0, 2, and 4 followed by q4w maintenance therapy with CZP 400 mg through Week 156 (3 years). Disease activity was measured using the Harvey Bradshaw Index (HBI). Here we examine the sustainability of remission (total HBI score of ≤4 points) in patients who were in remission at Week 4 of P4. Of the 124 patients who entered P4, 36% (n= 45) achieved remission by Week 4. After 1, 2, and 3 years of q4w CZP 400mgmaintenance therapy, remission was maintained in 56% (n= 25/45); 42% (n= 19/45) and 27% (n= 12/45) of patients, respectively. Remission rates for those who remained in the study and provided data at 1, 2, and 3 years (ie observed case analysis) were69%(25/36),76%(19/25), and67%(12/18), respectively. Rates of remission were similar in the continuous exposure and drug interruption groups. No new safety concerns were identified. No Caption available. No Caption available. Over two-thirds of patients who were recaptured with re-induction and maintained on q4w dosing were in remission at any observed point during the 1-, 2-, and 3-year treatment period. These data suggest that a long-term benefit is achieved with a re-induction strategy in patients with CD who lost response due to drug interruption or loss of initial response to active therapy with no dose escalation.

Long-term Maintenance of Remission with No Dose Escalation After Reinduction with Certolizumab Pegol in Patients with Crohnʼs Disease Exacerbation: 3-year Results from the PRECiSE 4 Study

Long-term Maintenance of Remission with No Dose Escalation After Reinduction with Certolizumab Pegol in Patients with Crohnʼs Disease Exacerbation: 3-year Results from the PRECiSE 4 Study

Immunsuppressive Therapie - Myasthenia gravis

Immunosuppressive therapy of myasthenia gravis is important for long-term maintenance of remission with minimal side effects. Indication for immunosuppressive treatment is dependent on the severity and course of the disease, and has to take into account the effect of thymectomy which is eventually performed in early-onset generalized myasthenia. Azathioprin is the only drug formally approved for treatment of myasthenia. However, a variety of other immunosuppressants, such as cyclosporine, mycophenolate, cyclophosphamide, and tacrolimus, have also been shown to be effective and can be prescribed off-label as second-line treatment in cases with inefficacy or intolerable side effects of azathioprine.

Long‐term Treatment With Autologous Red Blood Cells Loaded With Dexamethasone 21–Phosphate in Pediatric Patients Affected by Steroid‐dependent Crohn Disease

Inflammatory bowel disease (IBD) present in childhood in 15% to 25% of cases. The aim of therapy in children is not only to guarantee normal growth but also to prevent relapse and to maintain remission. Steroids are effective to induce remission; however, resistance, dependency, and irreversible side effects can develop. The aim of this study was to determine whether treatment with repeated infusions of autologous red blood cells (RBCs) loaded with dexamethasone 21-phosphate (Dex 21-P) is safe and allows maintenance of long-term remission in children with steroid-dependent Crohn disease (CD). Eighteen consecutive pediatric patients who met the inclusion criteria were admitted to the study. Infusions of autologous RBCs loaded with Dex 21-P were performed every 4 weeks; the mean duration of treatment was 24 months. At the beginning of treatment and after 6, 12, and 24 months, we performed clinical evaluation according to the Pediatric Crohn Disease Activity Index (pCDAI). Assessment of body mass in dexamethasone and bone mineral density by means of computerized bone mineralometry-dual energy x-ray absorptiometry, endoscopic evaluation, and hematic morning cortisol determination were also performed. During treatment, the mean pCDAI significantly decreased (P < 0.05); 78% of patients discontinued steroids. Determination of morning cortisol showed suppression only on the first day after infusion, followed by normalization of values. Endoscopic findings showed remission in 44% of patients. None of the patients experienced serious side effects. These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Maintenance of long-term remission using oral administration of low-dose etoposide in a patient demonstrating a relapse of blastic natural killer-cell lymphoma

Conflict of interest: none declared. Cutaneous manifestations are frequent in cases of blastic natural killer (NK)‐cell lymphoma, which is a rare malignant lymphoma. Blastic NK‐cell lymphoma has a poor prognosis, with repeated relapses, and most patients with this disease are elderly.1 It is therefore important to develop treatments that prevent relapse of this lymphoma without severe adverse effects, so that the quality of life of patients with this disease can be maintained. We report here a case of blastic NK‐cell lymphoma with relatively long‐term survival, in which the oral administration of low‐dose etoposide seemed to be useful for preventing relapse of the disease. A 72‐year‐old man presented with a tumour on the flexural region of his right forearm and multiple erythematous plaques on his back in December 2001. He had first become aware of a small tumour on his right forearm about 6 months earlier, and the tumour had been gradually increasing in size since then. He also noted multiple eruptions on his back early in December 2001.