Course Of Retreat Research Articles

Observational Characterization of the Retreatment Course of Patients With Thyroid Eye Disease.

To characterize the retreatment course of patients with thyroid eye disease (TED), who had reactivation after initial therapy with teprotumumab. This was a single-center longitudinal cohort study of patients who received an initial course of teprotumumab for active TED and were followed for at least 6 months. Reactivation was defined as the increase of proptosis of 2 mm or more or an increase in Clinical Activity Score (CAS) of two points or more, as adapted from the Optic-X study. Data collection included patient age, sex, smoking status, history of thyroidectomy or radioactive iodine, proptosis measurements, clinical activity score (CAS) before initial infusion of teprotumumab, time interval to reactivation, diplopia assessment by the Bahn-Gorman scale, CAS at the time of reactivation, and CAS and proptosis measurements after completion of retreatment and retreatment modalities, including clinical monitoring, corticosteroids, teprotumumab, and/or surgery. Among the reactivated cohort, the treatment response of patients who received a second course of teprotumumab was compared with patients who were treated with intravenous (IV) steroids. Twenty-six percent (11/42) of patients experienced reactivation of TED with an average time to reactivation of 9 (SD:5) months (range: 2-20 months), average CAS at reactivation of 4 (SD:1) (range: 3-7), and average increase in proptosis of 3 (SD:1) mm (range: 2-6 mm). Of the 11 patients who reactivated, 4 received a second course of teprotumumab, while 6 received IV steroids. One patient elected to monitor. The patients who received a second course of teprotumumab had a mean (SD) posttreatment CAS score of 0 reduction in proptosis of 4 (2) mm (range: 3-6). The patients who received IV steroids had a mean (SD) posttreatment CAS of 2 (1) (range: 1-4) and a reduction in proptosis of 0 (1) mm (range: [-1] to [2]). Univariate analyses to look at predictors of reactivation found no correlation between factors such as age, sex, duration of TED, smoking status, presence of diplopia, previous treatment with radioactive iodine, history of periorbital surgery, and/or thyroidectomy after initial completion of teprotumumab between the 2 cohorts. We found a significant correlation between the CAS scores before initial treatment (P = 0.036) and thyroid hormone dysregulation (P = 0.006) in those who experienced reactivation. Patients with TED may experience reactivation of the disease after initial therapy with teprotumumab. Reactivated disease responds to repeat therapy with teprotumumab with higher previous CAS and thyroid hormonal dysregulation being the variables that were significantly associated with reactivation. These data underscore the importance of long-term monitoring and exploring underlying triggers for disease reactivation. Understanding these factors could help predict which patients may require retreatment or chronic dosing with teprotumumab. Further studies are essential to advance our understanding of the immunomodulatory effects of teprotumumab, duration of its therapeutic benefit, and potential retreatment strategies to improve long-term patient outcomes.

Re-treatment of failed maxillary implant sites with severe bone loss from peri-implant disease: case series

Background: Peri-implant disease is a major challenge for the long-term success of implant-supported therapy and may result in implant removal and the need for re-treatment. The manuscript provides a step-by-step algorithm for the management of severe implant failure and the means required for a predictable re-treatment course.

NIMG-81. EFFECT OF RE-TREATMENT WITH TEMOZOLOMIDE IN GRADE 2/3 IDH MUTANT GLIOMAS AT FIRST PROGRESSION

Abstract BACKGROUND Patients with WHO grade 2 and 3 IDHmt gliomas commonly receive temozolomide, with or without radiation therapy, as initial therapy. At progression, temozolomide is sometimes reinstated despite a paucity of data on effectiveness. METHODS We reviewed imaging outcomes of patients with grade 2/3 IDHmt gliomas re-treated with temozolomide at first progression between 2007 and 2019. RESULTS 15 subjects included six grade 2 and five grade 3 oligodendrogliomas, one grade 2 and three grade 3 astrocytomas. Median time between completion of first temozolomide course and initiation of re-treatment was 47 months (range, 8-126 months). Best treatment response after first progression by RANO criteria was stable disease in 10 and progressive disease in 5 patients. Median progression free survival with temozolomide re-treatment was 27.4 months (95% CI: [13.8, 41.2 months] and median overall survival 47.8 months (95% CI: [31.5, 125.6 months]). In 14 patients who had pre- and post- first tumor progression rate measurements, the mean rate of tumor growth by bidimensional product was 0.29 cm2/month (95% CI: [0.17, 0.42 cm2/month], p< 0.001) prior to first tumor progression versus 0.47 cm2/month (95 CI: [0.08, 0.85 cm2/month], p=0.021) during re-treatment with monotherapy temozolomide (prior vs after, p=0.371). The volumetric mean rate of tumor growth was 1.12 cc/month (95% CI: [0.31, 1.93 cc/month], p=0.010) prior to first tumor progression versus 1.29 cc/month (95% CI: [0.15, 2.43 cc/month], p=0.030) during temozolomide re-treatment (prior vs. after, p=0.802). CONCLUSION Among 15 patients with progressive IDHmt glioma re-treated with temozolomide, there was no radiographic response by RANO criteria nor a decrease in tumor growth rate during the re-treatment period compared to immediate pre-re-treatment period. These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to temozolomide, underscoring the need for novel therapies.

Sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for treating patients with hepatitis C virus reinfection following direct‐acting antiviral‐induced sustained virologic response

AbstractData regarding the patient characteristics of hepatitis C virus (HCV) reinfection following viral eradication by a prior course of direct‐acting antivirals (DAAs) and the clinical performance of pangenotypic DAAs to retreat such patients are lacking. The demographics and potential routes of transmission were shown in 22 patients with confirmed reinfection following HCV clearance by a prior course of DAAs. Twenty patients received retreatment with pangenotypic sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) according to label recommendations. The sustained virologic response (SVR12) rates and the tolerance following treatment were reported. The incidence rates of reinfection among human immunodeficiency virus (HIV)‐positive and HIV‐negative patients were 8.33 per 100 person‐years (95% CI: 5.33‐12.78) and 0.30 per 100 person‐years (95% CI: 0.12‐0.77), respectively. Eighteen (81.8%) patients had HIV coinfection. The elapsed time between SVR12 and reinfection ranged from 3 to 36 months. Twenty (90.9%) patients had different viral genotypes/subtypes before and after HCV reinfection. Prior to reinfection, 15 (68.2%) patients achieved SVR12 using SOF/VEL or GLE/PIB. Twelve and eight patients were retreated with SOF/VEL for 12 weeks and GLE/PIB for 8 weeks, respectively, in whom SVR12 was all achieved. All patients completed the assigned course of retreatment without interruption and all had excellent tolerance. The risk of HCV reinfection is higher in HIV‐positive patients than HIV‐negative patients following DAA‐induced SVR. Treating reinfected patients with SOF/VEL or GLE/PIB as DAA‐naïve patients has excellent effectiveness and tolerance, irrespective of the type of prior DAA exposure or viral genotypes/subtypes.

Analysis of influencing factors and Bayesian network model study of treatment outcome in tuberculosis patients in Qinghai

Objective To analyze the influencing factors for treatment outcome in tuberculosis (TB) patients registered in Qinghai province from 2011 to 2019, infer the causal effect by establishing the Bayesian network model, and provide scientific evidence for the TB prevention and control in Qinghai. Methods The TB cases information registered in Qinghai from 2011 to 2019 were collected from the National Tuberculosis Management System for a descriptive analysis on the treatment outcomes of TB patients, and multivariate Logistic regression analysis was used to identify the factors affecting the treatment outcomes of TB patients. The influencing factors with statistical significance were used in the Bayesian network model for causal correlation and conditional probability inferences. Results There were 35 910 TB patients in Qinghai from 2011 to 2019, and 31 908 cases were treated successfully, with a success rate of 88.86%. The results of multivariate Logistic regression analysis showed that clinical consultation, referral, follow-up and diagnostic type were protective factors affecting the treatment outcomes in TB patients, while older age (≥ 55 years old), being farmers and herdsmen, being detected in health examination and other contact examination, severe disease, retreatment and non-full course management were the risk factors. The Bayesian network model concluded that the source of patients, disease severity and management mode had casual correlation with the treatment outcomes in TB patients. The mild TB patients who had sought medical care and received full cause supervision management had highest treatment success rate (95.63%) and the lowest probability of adverse outcome (4.37%). Conclusion Age, occupation, source of patients, diagnostic type, disease severity, treatment classification and management mode were the influencing factors of treatment outcomes in TB patients. The causal relationship and intensity between TB patient treatment outcome and influencing factors were revealed by establishing Bayesian network model. The model showed that the treatment success rate was highest in mild TB patients who sought medical care due to illness and received full-cause supervision management.

Factors Determining Retreatment Time Interval of Rituximab in Korean Patients With Rheumatoid Arthritis.

Unlike other biologic agents for rheumatoid arthritis (RA) that are administered at regular intervals even without flare, rituximab can be administered according to the timing of retreatment determined by the physician. Recently, there has been a tendency to prefer on-demand administration for disease flares rather than regular retreatment. We aimed to investigate the retreatment patterns of rituximab in patients with RA and to identify factors associated with extension of the time interval between retreatment courses. This study included RA patients on rituximab treatment who were enrolled in the Korean Rheumatology Biologics registry (KOBIO) or treated at Ajou University Hospital. Previous or current concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), corticosteroids, number of previous biologic agents, withdrawal, and time intervals of rituximab retreatment were collected. In case of treatment failure, the reasons such as lack of efficacy, adverse events, and others, were also identified. A total of 82 patients were enrolled. The mean follow-up period from the first cycle of rituximab was 46.1 months, and the mean interval between the retreatment courses was 16.3 months. The persistent rates of rituximab after 5 years was 72.4%. Concomitant use of at least two csDMARDs (β = 4.672; 95% CI: 0.089–9.255, p = 0.046) and concomitant use of corticosteroids (β = 7.602; 95% CI: 0.924–14.28, p = 0.026) were independent factors for extending the time interval between the retreatment courses. In conclusion, RA patients treated with rituximab in Korea show high persistence rates. Concomitant use of two or more csDMARDs and concomitant use of corticosteroids with rituximab are associating factors of extending the retreatment time interval. These findings should be considered when selecting rituximab as a treatment for patients with RA.

Single Fraction LINAC-Based SRS Re-Treatment of Brain Metastases Using Conservative Doses

We sought to evaluate the efficacy and safety of single fraction stereotactic radiosurgery (SRS), using conservative doses (relative to maximum tolerated doses from RTOG 9005), for brain metastases that recurred after initial SRS also with conservative doses.Under an IRB approved protocol, brain metastases that underwent retreatment with single-fraction, LINAC-based SRS were identified from 2014-2018. For each treated brain metastasis, histology, prescribed dose, lesion size, local control, and symptomatic radiation necrosis were recorded. Control was analyzed by Kaplan-Meier and Cox models.From an initial database containing 597 individual lesions210, 52 lesions in 22 were identified that recurred after initial SRS, for a total of 59 courses of retreatment (with some lesions being treated 3 times). Of the 52 initial lesions, 16 were from breast, 23 non-small cell lung, 9 melanoma, and 4 colorectal primaries. The median size and volume at first treatment were 0.9 mm and 1.47 cc respectively (ranges 0.3-31 mm and 0.2-13.4 cc respectively). Median dose covering 99% of the PTV was 14.6 Gy on initial treatment (10.7-18.2 Gy). Median time to re-treatment was 6.0 months (1-31). The median size, volume, and 99% PTV dose at re-treatment was 1.4 cm, 2.76 cc, and 15 Gy respectively. Both size (P = 0.006) and volume (P = 0.04), but not prescribed dose (P = 0.06) were significantly different when comparing initial and re-treatment lesion and treatment characteristics. The crude local control at 6 months was 58% after initial treatment (with 42% of recurrences occurring at > 6 months), and 70% after re-treatment (P = 0.02). Seven lesions in 6 patients developed symptomatic radiation necrosis after retreatment, 3 confirmed pathologically, 2 by magnetic resonance spectroscopy, and the remainder by imaging characteristics in absence of CNS progression. The mean normal brain V10 for the re-treatment course was 6.4 cc (range 3.8-18.4 cc) in these lesions. In a Cox multivariate model including: initial versus retreatment course, lesion volume, and PTV, retreatment was associated with improved local control (0.49, HR 0.29-0.83 P = 0.008).In this series of single fraction SRS using conservative doses, re-treated lesions showed improved control relative to initial treatment without significant increases in prescription dose in subsequent courses. These findings suggest that a threshold effective dose was not met on initial course but was able to be successfully made up later. Symptomatic necrosis after retreatment was relatively high, despite relatively low V10.M.A. Cummings: None. K.Y. Usuki: None. S. Hardy: None. M.T. Milano: Honoraria; UpToDate, self.

The Role of Hypofractionated Radiation Therapy in the Management of Unresectable Hepatocellular Carcinoma (HCC)

Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity.We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity.149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BEDα/β = 10) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement).SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.

Hävituspataljonidest Eestis 1941. aasta sõjasuvel [Abstract: The Destruction Battalions in Estonia in the Summer War of 1941

Hävituspataljonidest Eestis 1941. aasta sõjasuvel [Abstract: The Destruction Battalions in Estonia in the Summer War of 1941

Laboratory Parameters after Treatment for Loa loa and Mansonella perstans: The Experience of a Single Referral Center for Tropical Diseases in a Non-Endemic Area.

Infections due to Loa loa and Mansonella perstans are common yet elusive neglected filariases. Parasitological cure after treatment is very difficult to assess, as adult parasites are not accessible. Therefore, outside transmission areas, patients require a long follow-up period to ascertain the therapeutic outcome, which is impractical for non-sedentary populations such as migrants. We studied the change over time of microfilaremia, eosinophil counts, and antifilarial antibodies tested with a commercial ELISA test (Bordier Affinity Products, Crissier, Switzerland), in a retrospective cohort of patients with confirmed L. loa and M. perstans infections, to evaluate the role of serology in clinical practice. After treatment, all 22 eligible patients diagnosed in our center between 2015 and 2017 reached amicrofilaremia, with microfilarial counts decreasing sharply within 2 months. Paralleling eosinophil counts, antibodies decreased in all patients, 36% of whom reached sero-reversion or near-sero-reversion in < 20 months. These findings suggest that positive serology is not just residual from a past infection, and may be used for diagnosis even when microfilaremia is negative or cannot be performed. Interestingly, antibodies and eosinophil counts increased following some, but not all, re-treatment courses. If the rise in these parameters reflects death of macrofilariae, caution is required in interpreting high eosinophil counts and antibody titers shortly after treatment, as these may reflect no need for further treatment. To optimize patients' management, it is now pivotal to ascertain the interval between treatment and macrofilarial death and therefore whether re-treatments are required for complete clearance of parasites.

THUR 177 Efficacy of alemtuzumab retreatment after 2 initial courses

Efficacy of alemtuzumab retreatment (course [C] 3) after the initial 2 courses were evaluated (CARE-MS II, NCT00548405; extension, NCT00930553). Patients received alemtuzumab retreatment (12 mg/day, 3 consecutive days;≥12 months apart) as needed for relapse and/or MRI activity or another disease-modifying therapy (DMT) per investigator’s discretion. Assessments 12 months before C3 and up to 3 years after C3: annualised relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus core study baseline); 6 month confirmed disability improvement (CDI). Patients receiving another DMT were excluded. Analyses included patients who received C3 or more, with data censored at the time of C4 if a fourth course was received. Through Year 6, 88% of patients entering the extension remained on study, with 45% receiving ≥1 retreatment. ARR decreased from 0.85 (12 months before C3) to 0.20 (12 months after C3; rate ratio [95% CI], 0.24 [0.17–0.34]; p&lt;0.0001), and remained low (0.27) 3 years after C3. 68% of patients maintained stable/improved EDSS 12 months after C3. The percentage with CDI increased from 4% (12 months before C3) to 14% (12 months after C3; p=0.0126). These findings demonstrate the efficacy of alemtuzumab C3 in patients with disease activity after the initial 2 courses.Study support: Sanofi and Bayer HealthCare Pharmaceuticals.

Analysis and treatment of 45 platinum-allergic gynecologic malignant tumors.

This study aimed to explore the potential risk factors of platinum allergy and follow-up treatment to provide a reference for the clinical prevention and treatment of platinum allergic reactions in patients with gynecological tumors. The study retrospectively analyzed 45 cases of platinum allergic reactions that occurred in Shengjing Hospital affiliated to China Medical University from August 2010 to July 2016. Analysis of risk factors included the cumulative dose, treatment course and time intervals. The cumulative carboplatin dose in allergic patients ranged from 900 to 10250mg (average 4845mg). The 45 allergic reactions occurred between the 3rd and 25th course of treatment (average 11.4 courses). The average re-treatment interval of carboplatin-allergic patients was 28.1 months, including 93.3% of patients with platinum re-treatment interval of more than 1year. The allergic reaction occurred in the 2nd or 3rd course of re-treatment in 26 patients, accounting for 70.3% of all patients with recurrence. Seventeen patients were subjected to desensitization therapy, among which 13 cases were well tolerated. Patients who received more than 8 courses of carboplatin or a cumulative dose of more than 3500mg were the high-risk population for platinum allergy. The 2nd and 3rd treatment course after restarting carboplatin treatment after an interval time of more than 1year was the high incident period of carboplatin allergy. Skin tests should be conducted in patients with high risk of carboplatin allergy. In cases of carboplatin allergy, patients could receive carboplatin or oxaliplatin desensitization therapy.

LTBK-01. UPDATES ON THE PHASE II AND RE-TREATMENT STUDY OF AZD6244 (SELUMETINIB) FOR CHILDREN WITH RECURRENT OR REFRACTORY PEDIATRIC LOW GRADE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

AbstractThe PBTC is conducting a phase II study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/refractory LGG assigned to 6 strata. We present the updated data on Stratum 2 and 5. Also, data on subsequent progression after treatment completion in patients enrolled on Stratum 1 and 3 will be discussed. Finally, we present details on the re-treatment study (PBTC-029C). Both stratum 2 (pilocytic astrocytoma [PA] without common BRAF aberrations) and Stratum 5 (non-pilocytic LGG with BRAF aberrations) met response criteria for expansion (> 2 objective responses in 16 patients), and accrual to a total of 25 patients on each stratum is ongoing. Among 50 patients treated on Stratum 1 (PA with BRAF aberrations) or Stratum 3 (NF-associated LGG), 21 have progressed. Thirteen of 21 have progressed after stopping therapy. The median time to progression for these 13 patients is 119 days (10–928). The re-treatment study has enrolled 25 patients who received a median of 12 re-treatment courses (2–36). The most common attributable toxicities after re-treatment were grade 1 CPK elevation (44%), diarrhea (44%), hypoalbuminemia (40%), elevated AST (36%), rash (36%) and fatigue (32%). The most common grade 3/4 attributable toxicities were grade 3 paronychia (8%), CPK elevation (4%), AST elevation (4%), decreased ejection fraction (4%), neutropenia (4%), elevated triglycerides (4%), peripheral neuropathy (4%) and grade 4 CPK elevation (4%). There is not a significant difference between the toxicities observed during original therapy versus re-treatment. The most current response and patient demographic data will be presented.

Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response.

To evaluate the efficacy and toxicity of a repeat peptide receptor radionuclide therapy (PRRT) course in neuroendocrine tumour patients who have progressed following previous PRRT and to identify factors contributing to retreatment outcomes. This was a retrospective analysis of 47 consecutive patients who had been treated with PRRT (PRRT1) and following disease progression were retreated with a second course of PRRT (PRRT2). We reviewed patient, tumour and treatment characteristics, time to progression after PRRT1 and PRRT2, overall survival and toxicity. We evaluated Kaplan-Meier survival plots, multiple regression analysis on factors predictive of time to progression and toxicity. PRRT1:45/47 patients were initially were treated with 90Y-DOTATATE, with two patients treated with 177Lu-DOTATATE. The median progression free survival (PFS) following PRRT1 was 30 months [95% confidence interval (CI) (26.9-36.6 months)]. Two patients developed Grade1 renal toxicity. 3/47 patients had bone marrow toxicity, with 1 of these patients having Grade3 toxicity. PRRT2: At the second course of treatment, 29 patients were treated with 90Y-DOTATATE and 18 patients with 177Lu-DOTATATE. Of the 44 patients with evaluable survival data, 41 patients developed disease progression. The median PFS after PRRT2 was 17.5 months [95% CI(11-23.8 months)]. There was no statistically significant difference in median PFS dependent on the choice of radiopharmaceutical: median PFS for 177Lu-DOTATATE = 17.2 months, median PFS for 90Y-DOTATATE = 17.3 months. Male sex and high burden of liver metastases were associated with shorter PFS following a PRRT retreatment course. 17/41 (41%) patients had bone marrow toxicity (2/17 had Grade 3 toxicity; no Grade 4 toxicity was seen). One patient developed myelodysplastic syndrome. 6/41 (14.6%) developed Grade 1 renal toxicity and 1/41 (2.4%) had Grade 4 renal toxicity. The median overall survival from commencement of first PRRT cycle was 71 months. PRRT retreatment is safe and offers patients, who had progressed following initial PRRT course, a reasonably good PFS. Extra consideration is needed in patients with multiple comorbidities, as they may be at greater risk of renal and haematological toxicity. Male sex and high burden of liver metastases seem to be associated with shorter PFS following PRRT retreatment. The majority of studies on PRRT have shown that it is effective as an initial treatment. This study with long-term follow-up demonstrates that PRRT is safe and effective retreatment option in patients that have progressed following initial PRRT course.

Doses of rituximab for retreatment in rheumatoid arthritis: influence on maintenance and risk of serious infection.

To investigate maintenance of rituximab (RTX) in RA patients re-treated with reduced doses compared with standard dose in a real life setting. The Autoimmunity and Rituximab (AIR) registry is a nationwide prospective observational cohort investigating the long-term safety and efficacy of RTX in RA. The present study included patients from the AIR registry that have been re-treated with RTX after a first course of RTX standard dose (1000 mg × 2). Two groups were defined according to dose of RTX of the first retreatment course (i.e. second course): standard dose group and reduced dose group. Five years' maintenance and rate of serious infections of the retreatment period were compared between standard dose and reduced dose groups. Analyses used the inverse probability of treatment weighting propensity score adjusted method. Among the 1986 patients from the AIR registry, 1278 were included, 1093 (85.5%) treated with standard dose and 185 (14.5%) with reduced doses. Maintenance of RTX at 5 years in the standard and reduced groups was 55.5 and 53.8%, respectively, and did not significantly differ between groups in adjusted analyses (hazard ratio = 1.03; 95% CI: 0.81, 1.30), but the cumulative RTX dose received for retreatment [1.4 (0.6) vs 2.3 (1.0) g/year, P < 0.001] and the rate of serious infections were significantly lower in the reduced dose group (adjusted hazard ratio = 0.50; 95% CI: 0.27, 0.92; P = 0.02). Use of reduced doses of RTX for retreatment did not alter the maintenance of RTX at 5 years in RA patients, but allowed a 39% total dose reduction and a lower rate of serious infections.

Update on the Management of Diarrhea-Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline.

Diarrhea-predominant irritable bowel syndrome (IBS-D) is one of the most common diagnoses made by gastroenterologists. Current pharmacologic treatments for IBS-D include fiber supplements, antidiarrheal over-the-counter medications, probiotics, antispasmodics, antidepressants, and a 5-hydroxytryptophan 3 receptor antagonist. All of these options have limited efficacy in managing IBS-D. Rifaximin, a nonabsorbable antibiotic, has been evaluated in patients with IBS-D. In two randomized, double-blind, placebo-controlled phase III trials evaluating rifaximin 550 mg by mouth 3 times/day for 14 days, the primary efficacy end point was achieved by 9% more patients randomized to the rifaximin group compared with placebo (40.7% vs 31.7%, p<0.001, number needed to treat ~11). The primary efficacy end point was defined as the proportion of patients having adequate relief of global IBS symptoms for at least 2 of the 4 weeks during the primary follow-up period (weeks 3-6). In the phase III trial examining the efficacy and safety of repeated courses of rifaximin in patients who responded to the initial 2-week course, rifaximin given for up to two additional courses provided a statistically significant incremental benefit (33% vs 25%, p=0.02). Eluxadoline is a gut-targeting μ and κ opioid receptor agonist and a δ opioid receptor antagonist. The dual mechanism of eluxadoline may explain the antidiarrheal and abdominal pain-modulating properties and lack of profound constipation. In two identically designed randomized, double-blind, placebo-controlled phase III studies, 10.3% more patients in an eluxadoline 100 mg by mouth twice/day group met the primary efficacy end point during the follow-up 1-12 week period compared with placebo (p<0.001). The primary efficacy end point was a composite response, defined as improvement in worst abdominal pain and stool consistency at the same time on most (50% or more) days during the follow-up period. This review evaluates evidence for the use of rifaximin and eluxadoline in patients with IBS-D. Rifaximin provides an additional modality for the management of IBS-D patients; it has mild to moderate efficacy similar to other currently available treatment options. Rifaximin is relatively safe, lacks significant drug-drug interactions, and can be used for up to two additional retreatment courses. This may make rifaximin a possible initial or second-line treatment option. Eluxadoline can also offer relief to patients with IBS-D. While effective, because of several limitations, including drug-drug interactions and drug disease contraindications, as well as current lack of clinical experience, it may be tried as a second- or third-line agent.

FRI0026 Correlation between Serum Rituximab Level and Clinical Response in Rheumatoid Arthritis Patients Treated with B Cell Depletion Therapy

BackgroundRituximab (RTX) sustained efficacy in rheumatoid arthritis (RA) patients can be achieved by repeated courses of RTX (1). The correlation between serum drug level before a new retreatment and clinical...

SAT0228 Sustained Clinical Benefit with Multiple Courses of Rituximab in Second Line for ALL Rheumatoid Arthtritis Patients Irrespective to the Inhibitor of Tumour Necrosis Factor Previously Used: 3-Year Data from REPEAT Study

BackgroundIn the last decade, biologic therapy changed dramatically treatment options for rheumatoid arthritis (RA). However, a significant number of patients failed to maintain the initial response to a TNF blocker....

AB0422 Serum Drug Level and Anti-Citrullinated Peptide Antibodies as Biomarkers That Predict Eular Response in Rheumatoid Arthritis - A New Step to Personalized Medicine

BackgroundRituximab (RTX) therapy for rheumatoid arthritis (RA) exhibit enhanced effectiveness in patients with positive rheumatoid factor and/or anti-citrullinated peptide antibodies (ACPA). These two findings seem to predict clinical response (1)....

THU0261 Correlation between Time to Switch and Clinical Response Amplitude to Rituximab in Second Line Treatment in Rheumatoid Arthritis Patients with Treatment Failure to Tumor Necrosis Factor Inhibitors: 3-Year Data from Repeat Observational Study

BackgroundIn recent years we assist to an increasing interest to get more clinical data to improve the control of disease course in rheumatoid arthritis (RA) patients. According to treat to...