Incidence Of Clinical Relapse Research Articles

Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review

BackgroundUse of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established. MethodsIn accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included. ResultsThe overall incidence of clinical relapse during washout periods ranging from 4.4–10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02–0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %. ConclusionsThis systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.

P-018 YI Which Patients Are at Risk for Clinical Relapse in Ulcerative Colitis? A Prospective Study

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by periods of remission and periods of relapse. Up to 25% of the patients in clinical remission will present with disease relapse over a 6-month period. Most studies determining risk factors for clinical relapse are retrospective and performed over an extended period of time, being subject to selection, report and intervention bias. We aimed to prospectively identify clinical, analytical and endoscopic variables associated with an increased risk of short-term clinical relapse in corticosteroid-free remission UC patients. Prospective, observational study, including consecutive patients previously diagnosed with UC observed in our institution at scheduled consultations. During enrollment, only patients currently under medication for UC, in sustained corticosteroid-free remission and minimum follow-up of 6 months were included. Clinical and analytical variables were registered at enrollment, as well as recent (<6 months) endoscopic studies performed during clinical remission, current medication, and patient-reported adherence to prescribed medication. Patients were prospectively followed for 6 months, and clinical relapse (defined as the need to change or intensify treatment, hospitalization or surgery) was assessed. Statistical analysis was performed using SPSS v21.0, using univariate analysis with chi-square-test and independent-samples t-test; P value <0.05 was considered statistically significant. Included 135 patients, 56.3% female, mean age 44 (±13) years, and mean disease duration 6.4 (±4.8) years. Most patients (73%) were non-smokers, 20% were former smokers and 7% were smokers; familial history of IBD was present in 12% of the enrolled patients. Mean laboratorial values were within the normal range, except for slightly elevated c-reactive protein levels (7.9 ± 6.2 mg/L). The Mayo endoscopic score was ≤1 in 65% of the patients, and >1 in 35%. Disease extent was classified as proctitis in 47% of the patients, left-sided colitis in 35% and extensive colitis in 18%. Patients' medication included aminosalicylates in 91% of the cases, thiopurines in 17% and anti-TNFα agents in 13%. During follow-up, clinical relapse was observed in 14.1% (n = 19) of the patients. Age at enrollment <40 years (21.8% versus 8.8%, P = 0.032), disease duration <8 years (17.3% versus 3.2%, P = 0.048), disease flare during the previous year (40.0% versus 12.0%, P = 0.034), Mayo endoscopic Score >1 (50.0% versus 3.1%, P < 0.001) and partial or non-adherence to prescribed medication (30.0% versus 11.3%, P = 0.038) were significantly associated with an increased risk of clinical relapse during follow-up. The risk of relapse at 6 months was not associated with smoking status, disease extent, familial history of IBD, prescribed medication for UC or any analyzed laboratorial variable. In this prospective, observational study, there was a 15% incidence of clinical relapse at 6 months. This risk was significantly increased in younger patients (P = 0.032) with a shorter disease duration (P = 0.048), patients with recent disease flares (P = 0.034) or non-adherent to medication (P = 0.038), as well as patients where mucosal healing was not achieved (P < 0.001). In these patients in clinical remission, a lower threshold to intensify or change medication should be considered, and the importance of adherence to treatment should be reinforced.

Mucosal Healing in Ulcerative Colitis--When Zero is Better.

Extensive evidence has underlined the importance of mucosal healing as a treatment aim for ulcerative colitis (UC). We aimed to assess differences in the incidence of clinical relapse at 12 months between UC patients with Mayo endoscopic scores (MES) 0 and 1. This retrospective study included consecutive patients in corticosteroid-free remission between 2008 and 2013 and with follow-up of at least 1 year, with MES 0 or 1 in complete colonoscopy. Clinical relapse was defined as need for induction treatment, treatment escalation, hospitalization or surgery. A p value <0.05 was considered statistically significant. The study included 138 patients, 72 (52.2%) female, with mean age of 49 (±14) years. Inflammatory activity was classified as MES 0 in 61 (44.2%) patients and MES 1 in 77 (55.8%) patients. Clinical relapse during follow-up was significantly more frequent in patients with MES 1 than MES 0 (27.3 vs 11.5%, p = 0.022), and in the multivariate analysis MES 1 was the only factor significantly associated with an increased risk of relapse (odds ratio 2.89, 95% confidence interval 1.14-7.36, p = 0.026). This association was encountered in the subgroup of patients with left-sided/extensive colitis (29.7 vs 11.1%, p = 0.049), but not proctitis (25.0 vs 12.0%, p = 0.202). In patients with UC in corticosteroid-free remission, particularly those with left-sided colitis or extensive colitis, MES 1 was significantly associated with a 3-fold increased risk of relapse compared with endoscopic MES 0. Our results support the use of endoscopic MES 0 as the most suitable treatment endpoint to define mucosal healing in patients with UC.

Efficacy and tolerability of systemic methylprednisolone in children and adolescents with chronic rhinosinusitis: A double-blind, placebo-controlled randomized trial

The place of systemic corticosteroids in the treatment of children with chronic rhinosinusitis (CRS) remains unclear. We sought to assess the effectiveness and tolerability of oral methylprednisolone as an anti-inflammatory adjunct in the treatment of CRS in children. Forty-eight children (age, 6-17 years) with clinically and radiologically proved CRS were included. Patients were randomly assigned to either oral amoxicillin/clavulanate (AMX/C) and methylprednisolone or AMX/C and placebo twice daily for 30 days. Oral methylprednisolone was administered for the first 15 days with a tapering schedule. Primary parameters were mean change in symptom and sinus computed tomographic (CT) scan scores after treatment. Secondary study parameters were mean changes in individual symptom scores after treatment, relapse rate, and tolerability. Forty-five patients completed the study: 22 received AMX/C and methylprednisolone, and 23 received AMX/C and placebo. Both groups demonstrated significant improvements in symptom and sinus CT scores when comparing baseline values with end-of-treatment values (P< .001). Methylprednisolone as an adjunct was significantly more effective than placebo in reducing CT scores (P= .004), total rhinosinusitis symptoms (P= .001), and individual symptoms of nasal obstruction (P= .001), postnasal discharge (P= .007), and cough (P= .009). At the end of treatment, 48% of the children in the placebo group still had abnormal findings on CT scans versus 14% in the methylprednisolone group (P= .013). Therapy-related adverse events were not different between groups. Although insignificant, the incidence of clinical relapses was also less in the methylprednisolone group (25%) compared with that in the placebo group (43%, P= .137). Oral methylprednisolone is well tolerated and provides added benefit to treatment with antibiotics for children with CRS.

Differential effect of adjuvant taxane-based and taxane-free chemotherapy regimens on the CK-19 mRNA-positive circulating tumor cells in patients with early breast cancer.

10554 Background: To investigate the effect of adjuvant taxane-free and taxane-based chemotherapy regimens on the elimination of circulating tumor cells (CTCs) in patients with early breast cancer. Methods: The presence of CK-19 mRNA-positive CTCs in the peripheral blood was evaluated both before and after chemotherapy, using a real-time RT-PCR assay, in 545 women with stage I-III breast cancer who received adjuvant taxane-free (FE75C and E75C) or taxane-based (sequential docetaxel followed by epirubicin/cyclophosphamide or docetaxel/epirubicin) chemotherapy. Results: Taxane-based regimens were more effective than taxane-free regimens in the elimination of CTCs since 49.7% and 33.0% of patients with detectable CTCs before chemotherapy, respectively, became CK19 mRNA-negative after completion of chemotherapy (p=0.015). The incidence of clinical relapses was higher in patients treated with taxane-free than in those treated with taxane-based (33.2% and 16.6%, respectively, p=0.00001). Patients treated with a taxane-free regimen had a significantly lower DFS compared to patients treated with a taxane-based chemotherapy (p=0.035); this difference was observed in patients with but not without detectable CTCs before chemotherapy (p=0.018 and p=0.481, respectively). Multivariate analysis revealed that the chemotherapy regimen was significantly associated with a prolonged DFS (HR: 2.00; 95% CI: 1.20-3.34) in patients with detectable CTCs. Conclusions: Elimination of CK-19 mRNA-positive CTCs during adjuvant chemotherapy may be an indicator of the efficacy of the chemotherapy regimen and this is associated with a favorable clinical outcome in patients with detectable CTCs

Effect of adjuvant treatment on the circulating CK-19 mRNA-positive tumor cells in patients with early stage breast cancer

20012 Background: To evaluate the effect of adjuvant treatment on the peripheral blood CK-19 mRNA circulating tumor cells (CTCs) in patients with early-stage breast cancer. Methods: CTCs were detected by real-time RT-PCR assay, in 119 patients with estrogen or/and progesterone receptors-positive tumors at the following time points: before the initiation and after the completion of adjuvant chemotherapy and every 3 or 6 months during the period of adjuvant tamoxifen administration. Results: Adjuvant chemotherapy failed to “eliminate” the CTCs in 17 (47%) out of 36 patients with detectable cells in pre-chemotherapy samples; in addition, adjuvant tamoxifen failed to “eliminate” the CTCs in 8 (36.4%) of 22 patients displaying detectable cells in post-chemotherapy samples. The incidence of clinical relapse was significantly (p = 0.017) higher for patients with post-chemotherapy detectable CTCs as well as for patients with persistently detectable CTCs throughout the follow-up period compared with those who did not (65.3% vs 7.3%, respectively; p &lt; 0.001). In multivariate analysis, post-chemotherapy detection of CTCs and their persistence throughout the follow-up period were significantly associated (p = 0.001 and 0.003, respectively) with early relapse. Conclusions: The detection of CK-19 mRNA+ CTCs after adjuvant chemotherapy and during tamoxifen administration is an independent prognostic factor associated with unfavorable outcome. No significant financial relationships to disclose.

Radical versus postoperative radiotherapy for localized prostate cancer: a 10-year experience of an academic hospital

This study is a presentation of our department's experience in the treatment of localized prostate cancer with either radical or postoperative radiotherapy (RT). Fifty-five patients with clinical localized prostate cancer were reviewed. Thirty-three patients (T1-T2AN0M0 stage) were treated with radical RT and 22 (T2B-T3N0M0 stage) with postoperative RT. All patients received hormonal therapy. Primary end points of the study were the incidence of clinical and biochemical recurrences and death in the whole group and according to treatment modality. Within a median follow-up of 18 months the overall incidence of clinical relapse was 16.9%, of biochemical relapse 12.7% and of death 10.9%. Both treatment options achieved similar outcomes despite the fact that the patients in the postoperative RT group were of higher stage. Radical RT group tended to have better overall and disease-free survival compared to postoperative RT group, but there was no statistically significant evidence. Long-term toxicity was negligible.