Mean Number Of Relapses Research Articles

TAURUS-MS II: real-world use of teriflunomide in Germany and changes in treatment patterns over time.

Teriflunomide is a once-daily oral disease-modifying therapy (DMT) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Only limited information is available about its real-world use and changes over time. To collect real-world data on teriflunomide use in clinical routine (and comparison to the previously conducted study TAURUS-MS). National, open, non-interventional, prospective, multicenter study. TAURUS-MS II was conducted at 220 German sites between July 2017 and March 2022, including RRMS patients treated with teriflunomide. Data on patient demographics, MS history, previous treatment, therapy satisfaction, and safety were collected. In total, 752 patients were included (65% female) with a mean age (±standard deviation) of 43 ± 11 years. Sixty-six percent had DMT before, and 46% had discontinued their last pretreatment ≤6 months prior to study entry. Among the latter, previous DMTs were interferon (21%), glatiramer acetate (11%), and dimethyl fumarate (9%), and reasons for discontinuation were adverse events (AEs; 55%) and insufficient efficacy (16%). Over 24 months, the mean treatment Satisfaction Questionnaire for Medication scores improved by 6 ± 29 points on effectiveness, 8 ± 20 on convenience, and 12 ± 25 on global satisfaction. The mean number of MS relapses decreased from 0.81 ± 0.81 in the 24 months prior to 0.27 ± 0.57 within 24 months after study entry. Non-serious AEs occurred in 423 patients (56%) and serious AEs in 49 patients (7%). Most reported AEs were alanine aminotransferase increase (11%), hypertension (8%), and alopecia (7%). Compared to TAURUS-MS, patients in TAURUS-MS II were younger, had a higher employment rate, and a higher share of treatment-naïve patients. Mean number of relapses was significantly reduced. Patient satisfaction was significantly improved compared to previous DMT. Tolerability was comparable to previous trials. Bundesinstitut für Arzneimittel und Medizinprodukte public database for non-interventional studies, number 7138.

10203-ML-6 TIRABRUTINIB FOR PRIMARY CNS LYMPHOMA: A SINGLE INSTITUTE RETROSPECTIVE ANALYSIS

Abstract In 2020, Tirabrutinib (TIR) was approved in Japan as a novel treatment for primary CNS lymphoma (PCNSL). However, the position of TIR in relation to the existing therapy, methotrexate (MTX)-based therapy, is still unclear. We are currently using TIR for patients who have insensitivity to MTX, have short-term recurrence after MTX, or have difficulty receiving MTX, with the principle of readministering MTX-based therapy to patients with recurrent disease. The subjects were ten patients treated with TIR at our institute, 6 with multiple relapses, 3 with inability to MTX, and 1 with difficulty in MTX treatment, and the mean number of relapses was 3.8 when Tirabrutinib was used. The mean number of treatments was 104 days, and 7 patients discontinued treatment due to tumor progression, while 3 patients discontinued due to severe skin problems. The median progression-free survival was 99 days, and only one patient was controlled for more than one year. 4 patients received the best supportive care for recurrence after TIR, and one patient received radiotherapy. The four patients in the MTX-based retreatment group had two progressions and two no progressions at the time of the abstract, with a progression-free survival of 133 days, and two patients had CTCAE grade 4 hematologic toxicities that had not occurred with previous therapy. One patient treated surgically died of postoperative pneumocystis pneumonia. Tirabrutinib showed a high early response rate, but the duration of tumor control tended to be shorter than with MTX-based retreatment. This may be due to its use in our institution after multiple relapses and its aggressive administration in MTX-naive patients. It is also important to note that chemotherapy after TIR use is associated with increased hematologic toxicity.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6months for 2years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and theTreatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18months (p = 0.004) and 29.0 (24.6) at 24months (p = 0.002). Levels of fatigue and depression were also reduced. After 2years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2years is effective in reducing ARR and disability progression.

A Study to Assess Burden on Caregivers of Opioid Use Disorder

Abstract Background: Substance use disorder is global problem associated with significant socio-occupational dysfunction. It has been increasingly realized that it should be conceptualized as affecting a family and not just an individual. This study aimed at assessing the caregivers’ burden in opioid dependence in a Tertiary Care Teaching Hospital in Punjab. Materials and Methods: This was a cross-sectional study where the sample comprised 50 patients diagnosed with opioid dependence, as per the International Classification of Diseases-10 criteria and their 50 caregivers. The caregivers’ burden was assessed with the help of the Montgomery Borgatta Caregiving Burden Scale, which is a subject-rated scale. Results: Most of the patients (54%) as well as the caregivers (30%) were 21–30 years of age, with male predominance and belonged to rural area, were unmarried, living in a nuclear family, and had a middle socioeconomic status. Most of the patients (88%) reported consuming “Heroin” and 64% reported using two or more than two substances. The mean age of first use of opioid was found out to be 21.8 years, the mean duration of the illness was 8.04 years, and the mean number of relapses was 2.94. About 58% of caregivers had moderate objective burden, 98% had severe subjective burden, and 78% had severe subjective demand burden. Conclusions: There is an urgent need to target the community awareness programs at the adolescent age group and a need to focus on the family rather than the individual patient, in the backdrop of the findings of this study.

To wait, or too late? Modeling the effects of delayed ofatumumab treatment in relapsing-remitting multiple sclerosis

BackgroundSeveral disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) reduce relapse rates and slow disease progression. RRMS DMTs have varying efficacy and administration routes; DMTs prescribed first may not be the most effective on relapses or disease progression. Here, we aimed to quantify the benefit of initiating ofatumumab, a high-efficacy DMT, earlier in the treatment pathway.MethodsAggregate data from a real-world cohort of patients with RRMS, who were eligible for dimethyl fumarate (DMF) or ofatumumab treatment within the UK National Health Service (N = 615), were used to produce a simulated patient cohort. The cohort was tracked through a discrete event simulation (DES) model, based on the Expanded Disability Status Scale (EDSS), with a lifetime time horizon. Outcomes assessed were: mean number of relapses, time to wheelchair (EDSS ≥7), and time to death. Two modeling approaches were used. The first compared outcomes between two treatment sequences (base case: ofatumumab to natalizumab versus DMF to ofatumumab). The second incorporated a time-specific delay of 1–5 years for switching from DMF to ofatumumab; the difference in outcomes as a function of increasing delay to ofatumumab are reported.ResultsCompared with delayed ofatumumab, fewer relapses and increased time to wheelchair were predicted for earlier ofatumumab in the treatment-sequence approach (mean relapses over the lifetime time horizon: 8.63 versus 9.00; time to wheelchair: 17.55 versus 16.60 years). Time to death was similar for both sequences. At Year 10, a numerically greater proportion of patients receiving earlier ofatumumab had mild disease (EDSS 0–3: 44.12% versus 40.06%). Greater differences, reflecting poorer outcomes, were predicted for relapses and time to wheelchair with increasing delays to ofatumumab treatment.ConclusionsThe DES model provided a means by which the magnitude of benefit associated with earlier ofatumumab initiation could be quantified; fewer relapses and a prolonged time to wheelchair were predicted.

Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients.

BackgroundHigh dose systemic glucocorticoid is the main therapy of treatment-naïve Vogt-Koyanagi-Harada (VKH) disease. However, series side effects induced by high dose systemic glucocorticoid frequently occur, which makes alternative therapy necessary for certain patients. This study sought to compare the efficacy and safety of systemic glucocorticoid-free (SGF) therapy with conventional therapy (CT) as an initial treatment for VKH patients.MethodsVKH patients who had not been systemically treated were enrolled. Patients were allocated into 2 therapeutic groups depending on their treatments. In CT group, patients received systemic glucocorticoid plus immunosuppressants (IS), and in SGF group, patients received adalimumab (ADA) plus IS. Patients received approximately 12 months treatment and visit monthly. The outcome parameters included the changes of best-corrected visual acuity (BCVA), intraocular inflammation (including anterior chamber cell grade and vitritis grade) and central macular thickness (CMT) (the change values define as the final-visit values subtracted from baseline counterparts). Other outcomes included the relapses times of ocular inflammation, adverse events (AEs), changes of optic nerve inflammation (ONI) and intraocular/extraocular manifestations.ResultsA total of 30 patients (60 eyes) were included. with 19 patients (38 eyes) in CT group and 11 patients (22 eyes) in SGF group. After approximately 1 year of treatment, the improvements of BCVA were slight better in the SGF group (0.57±0.23) than in the CT group (0.40±0.26), (P=0.014). In both groups, the ocular inflammatory improvements in both groups were similar, with an improvement of AC cell grade of −1.5 (−2, −0.5) in CT group versus −1 (−2, −1) in SGF group (P=0.367); improvement of vitritis grade was 0 (−1.25, 0) in CT group and −1 (−1, −1) in SGF group (P=0.050). The improvement in CMT was similar in both groups, with −523.47±412.09 µm in CT group and −362.73±375.73 µm in SGF group (P=0.572). The mean number of relapses was 1 (0, 2) in the CT group and 0 (0, 2) in the SGF group (P=0.372). No severe AEs were observed in this study.ConclusionsSGF therapy is effective, safe, and well-tolerated in treatment-naïve VKH patients. SGF therapy seems to be a feasible option in patients with existing systemic diseases intolerant to glucocorticoid.

Comparative Efficacy of Relapsing Multiple Sclerosis Therapies: Model-Based Meta-Analyses for Confirmed Disability Accumulation and Annualized Relapse Rate

BackgroundMultiple sclerosis (MS) is an inflammatory autoimmune disorder and the most common cause of non-traumatic disability in young adults. The Phase 3 OPTIMUM study evaluated the efficacy and safety of oral ponesimod, a selective sphingosine-1-phosphate (S1P) receptor 1 modulator, vs. teriflunomide in patients with relapsing multiple sclerosis (RMS). The aim of this analysis was to assess the effect of ponesimod and other disease modifying treatments (DMTs) compared to placebo, as measured by 12-week confirmed disability accumulation (CDA) and annualized relapse rate (ARR) in RMS patients. MethodsA database was developed by Certara Inc. (USA) based on relevant clinical trials identified from searching the following sources: PubMed, clinicaltrials.gov, FDA and EMEA documents, and conference abstracts. This database consisted of 203 unique randomized controlled trials (RCTs) with 74 MS treatments and was subsequently filtered to include RCTs with more than 25 patients receiving monotherapy to treat RMS for at least 48 weeks. A model-based meta-analysis (MBMA) was performed on the filtered database to assess treatment effects measured by CDA and ARR. Analyzed data for CDA were digitized from published Kaplan-Meier plots. A Weibull distribution was assumed to adequately capture the relationship of CDA probability over time, and hazard ratios (HRs) between treatments were assumed constant over time (proportional hazards). HRs were estimated for 12-week CDA for 17 DMTs vs. placebo. Additionally, mean ARR for each treatment arm was modelled, where relative effect versus placebo was estimated as a fixed effect parameter for each unique drug. A dose-response relationship was included if data for multiple doses were available. Relative treatment effect covariates explored for CDA and ARR included: percent of patients with relapsing-remitting MS (RRMS), trial start year, mean duration of disease, percent of patients who received DMTs within the prior 2 years (pDMT), mean number of relapses in the prior year, mean age, mean baseline EDSS score, and mean treatment duration (for ARR). ResultsThe 12-week CDA model utilized longitudinal data from 26 RCTs (18 unique treatments [including placebo]), 69 treatment arms, 31,160 patients). The ARR model utilized data from 40 RCTs (18 unique treatments [including placebo], 100 treatment arms, 33,686 patients). Compared to placebo, ponesimod significantly reduced 12-week CDA by 39% (HR: 0.61; 95% CI: 0.45–0.82) and reduced ARR by 53% (rate ratio [RR]: 0.47; 95% CI: 0.39–0.58). Except for three DMTs (interferon β-1b, glatiramer acetate, ozanimod), HR of 12-week CDA vs. placebo was significantly lower for the DMTs included in this analysis (HR range: 0.41 to 0.79). The ARR was significantly reduced for all DMTs compared to placebo (RR range: 0.29 to 0.82). A dose-response relationship indicated a potential dose-dependent effect (12-week CDA: 6 treatments; ARR: 8 treatments). Relative treatment effect was found to be significantly smaller in trials including more patients with prior DMT usage. Cross-trial heterogeneity in relative effects was assessed and found to be negligible; however, there is a possibility that confounders remain which may impact estimated relative treatment effects. ConclusionsCompared to placebo, ponesimod 20 mg significantly reduced both the risk of 12-week CDA and mean ARR, suggesting it has robust efficacy in the treatment of RMS.The study was funded by Janssen Research & Development, LLC.

RELATIONSHIP BETWEEN MYOPIC CHOROIDAL NEOVASCULARIZATION ACTIVITY AND PERFORATING SCLERAL VESSELS IN HIGH MYOPIA.

To study perforating scleral vessels (PSVs) in patients with high myopia using swept-source optical coherence tomography and to determine their relationship with myopic choroidal neovascularization (mCNV) and its activity. Retrospective analysis of patients with high myopia (≥-6 D or ≥26 mm of axial length) using multimodal imaging. The presence of PSVs and mCNV was assessed using swept-source optical coherence tomography images (TRITON; Topcon Corporation, Japan). Five hundred sixty-four eyes from 297 highly myopic patients were studied. One hundred fifty-five eyes (27.5%) showed signs of mCNV while PSVs were found in 500 eyes (88.6%). Perforating scleral vessels were found in 93.5% (145/155) of eyes with mCNV, and they were under or in contact with the mCNV in 80.6% (117/145). The mean number of intravitreal injections received by patients with mCNV was 4.06 ± 4.17 along 66.9 ± 4.1 months of follow-up. The number of injections per year was 1.32 ± 1.56, the mean number of relapses was 1.11 ± 1.83, and the mean number of relapses per year was 0.25 ± 0.41. Perforating scleral vessels are more common among highly myopic patients suffering from neovascular complications. Myopic CNV complexes that are coincident with PSVs on optical coherence tomography show higher rates of activity, needing more injections to control them and being more prone to relapses.

Factors Affecting the Statural Growth Retardation in Children using Steroids in Idiopathic Nephrotic Syndrome

Background and Aim: Idiopathic nephrotic syndrome or nephrosis causes massive protein leakage in the urine. Its treatment requires steroids (prednisone, methylprednisolone), often for a prolonged period, notably in case of steroid-dependence or steroid-resistance. In children, long-term use of steroids can lead to several side effects such as statural growth retardation/ stunting. This study evaluated the frequency of stunting in idiopathic nephrotic syndrome in children on steroids and identified the associated factors. 
 Material and Methods: This was a retrospective, descriptive cohort study carried out in children aged 0 to 16 years treated at the paediatric nephrology unit of Aristide Le Dantec Hospital in Dakar, between 1 December 2017 and 31 May 2020. All records of nephrotic children treated in outpatient or inpatient setting were included. These children had to be on corticosteroid therapy for at least 30 months and have a height taken regularly during follow-up consultations.
 Results: Of 259 children followed for idiopathic nephrotic syndrome, 93 were included in the study. The median age was 96.5 months and the sex ratio was 1.9. The mean height of the children at the beginning of the follow-up was -0.26 DS, at the end it was -0.88 DS. At the beginning of the follow-up, 8 children had already stunting. At 12 months follow-up, 72 children (77.4%) had a decrease in z-score; and at 30 months, there were 7 more children (84.9%) who had a decrease in z-score. Methylprednisolone boluses were given to 17 children (18.3%). Calcium supplementation was done in 91 children (97.8%). Vitamin D supplementation was given to 91 children (97.8%). The mean number of relapses was 1.8. Factors associated with stunting were number of relapses ≤3 (p=0.03), duration of corticosteroid therapy >6 months (p<0.0001) and cumulative doses of prednisone >100 mg/kg (p=0.04).
 Conclusion: In prolonged nephrotic syndrome in children, corticosteroids can cause stunting.

Belimumab for the treatment of children with frequently relapsing nephrotic syndrome: the BELNEPH study.

Effectiveness of rituximab in pediatric idiopathic nephrotic syndrome suggests that B cells play a pathogenic role. We tested safety and efficacy of the B-cell-modulating agent belimumab in frequently relapsing nephrotic syndrome (FRNS). An open-label, prospective, single-arm pilot study (EUDRACT 2017-003839-11) was designed to treat 10 children with FRNS with i.v. belimumab for 12 months. Prednisone was tapered/stopped. Safety, number of relapses, cumulative prednisone dose and B-cell subset "levels" are referred to both B cell subset and immunoglobulin. Five patients were enrolled, and four reached the primary 6-month endpoint. Of these, two completed the 12-month endpoint. Three patients experienced ≥2 relapses while on belimumab, requiring additional immunosuppression. Compared to the 6 months before belimumab treatment, the mean number of relapses (1.4 vs. 2, p=0.21) and the mean cumulative prednisone dose (1.86 vs. 2.62 g/m2, p=0.17) were not significantly reduced during the 6 months on belimumab. This study was terminated by the steering committee after the interim evaluation because belimumab failed to show clear benefits to counterbalance the inconvenience of monthly i.v. infusion. During follow-up, total and mature-naïve B cells decreased, while no change in memory B-cells was observed. Serum immunoglobulins remained stable. No infusion reaction was observed. Short-term treatment with belimumab in pediatric FRNS was well tolerated. The number of patients was too small to draw conclusions on efficacy. Nonetheless, we did not observe clear improvements. The burden of monthly in-hospital i.v. infusions outweighed potential benefits. Persistence of circulating memory B cells supports their pathogenic role in the disease. A higher resolution version of the Graphical abstract is available as Supplementary information.

Comparaison clinico-épidémiologique des pathologies du spectre des neuromyélites optiques

Neuromyelitis optica spectrum disorder (NMO-SD) has been recognized for the past decade. Biomarkers such as anti-Aquaporin 4 antibodies (AQP4) and anti-Myelin Oligodendrocyte Glycoprotein (MOG) have been able to classify NMO-SD into several groups. A retrospective study was performed in the Strasbourg University Medical Center among patients with AQP4+, MOG+ and double-seronegative NMO to compare their clinical, epidemiological and paraclinical features. Thirty-two patients with NMO were included. The AQP4+ NMO patients had a median of age of 45 years, with associated myelitis in 62.5% of cases and other autoantibodies in 37.5% of cases. The mean number of relapses by clinical history was 3. The mean initial visual acuity during an exacerbation was 0.3 LogMAR, and the visual acuity after an exacerbation was 0.1 LogMAR. MOG+NMO patients had a median age of 23 years, with severely impaired initial visual acuity (0.6 LogMAR) but better recovery (0 LogMAR); optic disc edema was present in 80% of cases; the mean number of relapses on clinical history was 1. AQP4-/MOG- NMO's were more common in women (70%) and were bilateral in 40% of cases. The diagnostic characteristics of NMO-SD are becoming increasingly differentiated, with a positive impact on functional prognosis and long-term progression. Other biomarkers have yet to be identified to improve the diagnosis and treatment of these disorders.

Adherence to self-administering interferon-β1a using RebiSmart® device in Mexican patients with relapsing multiple sclerosis.

BackgroundAdherence to disease-modifying therapies is determinant to attain maximal clinical benefit in multiple sclerosis (MS). RebiSmart® is an electronic auto-injector for subcutaneous delivery of interferon β-1a (INF-β1a) that monitors adherence by featuring a log of each drug administration for objective evaluation. The aim of this study was to assess long-term adherence to INF-β1a by using the RebiSmart® device in Mexican patients with relapsing MS.MethodsThis is an observational multicenter study on patients with relapsing MS treated with INF-β1a subcutaneously delivered by the RebiSmart® device. Adherence was computed as the number of injections received during the study period divided by the number of injections scheduled and expressed as percent.ResultsA total of 66 patients from 6 specialized MS centers were evaluated (45 females and 21 males, mean age 43.91±13.32 years). Mean adherence was 79.51±18% (median: 85.54%, range: 34.4–100%). During a median follow-up of 27.5 months (mean 33.36±29.39 months) the annualized relapse rate had a mean of 0.50±1.63. Mean initial EDSS was 1.90±1.52, and mean EDSS at the end of follow-up was 1.80±1.74. Compared with their counterparts, the mean number of relapses was significantly lower among patients with high (>80%) adherence (0.25±0.44 vs 0.67±92 relapses, respectively; P = 0.03). The proportion of relapse-free patients was 75.0% among patients with high adherence and 53.3% in low-compliant patients (P = 0.06). High adherence patients presented lower rates of EDSS worsening ≥1.0 at the end of treatment, as compared with low-compliant patients (11.1% vs 43.3%, respectively; P = 0.003). High schooling (>12 years) was the only predictor of a high adherence (OR: 2.97, 05% CI: 1.08–1.18; P = 0.03) and of being relapse-free during follow-up (OR: 3.22, 05% CI: 1.12–9.23; P = 0.03).ConclusionAdherence to INF-β1a using RebiSmart® in this Mexican cohort with MS was moderate, but associated with low relapse rate and influenced by high schooling.

Effect of pregnancy and exclusive breastfeeding on multiple sclerosis relapse rate and degree of disability within two years after delivery

ObjectivesPregnancy and lactation are important issues for women with multiple sclerosis (MS). The purpose of this study was to investigate the effect of pregnancy and exclusive breastfeeding on the rate of relapse and degree of disability within two years after delivery among patients with relapsing remitting multiple sclerosis (RRMS). Patients and Methods30 pregnant women with RRMS who had exclusive breastfeeding for 4 months were compared with 67 non-pregnant women with RRMS between 2012 and 2017. Each patient was examined every three months for 33 months. In the study group, patients were examined at the beginning of pregnancy, and then every three months till 24th months after delivery. ResultsIn the study group, Expanded Disability Status Scale (EDSS) during the third trimester of pregnancy, between four to nine month after delivery, and the last 6 months of the study were significantly lower than the control group (p < 0.05). At the end of the study, the mean EDSS of the study group was significantly lower than the control group (p < 0.05). Also, EDSS during the second and third trimesters of pregnancy were significantly lower than the EDSS before pregnancy (p < 0.05). The mean number of relapses in the second and third trimesters of pregnancy, between four to six months after delivery, and the total number of relapses were significantly lower than the control group. ConclusionPregnancy and exclusive breastfeeding can have a positive effect in reducing relapse rate and disability. This effect will continue until the 24th month after childbirth.

Quality of life in children with severe forms of idiopathic nephrotic syndrome in stable remission-A cross-sectional study.

Severe forms of idiopathic nephrotic syndrome (INS) require immunosuppressive therapy: oral treatment or intravenous therapy (rituximab, RTX). The main objective was to describe quality of life (QOL) in these specific patients. Cross-sectional, multicentre, observational study analysed QOL using a standardised questionnaire in children from 7 to 17years, with a steroid-dependent or steroid-resistant INS in stable remission. The questionnaire consisted of 30 questions concerning physical and emotional well-being, self-esteem, family, friends, school and disease resulting in a global score of 0-100. A total of 110 patients with a mean age of 11.6years from three French paediatric nephrology centres were included. A total of 71 patients had oral immunosuppressive treatment, 27 had RTX, and 12 had both. 13.6% of patients had a steroid-resistant INS. The mean number of relapses was 5.8. Seventy-eight patients answered the questionnaire. The global score in the whole study population was 74.7; 72.6 in the RTX group, 76.2 in the oral drugs group, (P=0.49). The results of sub-dimension 'school' were statistically lower in RTX group (61.6±19.5) compared with oral drugs group (71.4±16; P=0.02). Global QOL score was high in 'difficult-to-treat' patients with INS in stable remission on oral immunosuppressive or RTX treatment.

Rituximab versus cyclophosphamide for the treatment of children with steroid resistance nephrotic syndrome; a clinical trial study

Introduction: The most common complications of the nephrotic syndrome (NS) are the frequent relapses, steroid resistance, and long-term steroid administration. Objectives: This study aimed to compare the therapeutic effect of rituximab versus cyclophosphamide in the prevention of relapses and the complications of treatment in children with steroid-resistant NS. Patients and Methods: This clinical trial study was performed on 50 patients with resistant steroidal NS referred to Masoumeh hospital in Qom, Iran. Patients were randomly divided into the two groups including intervention (n=20) and control groups (n=30). In addition to the prednisolone, the intervention group received 375 mg/m2/weekly rituximab intravenously for 4 weeks. The control group received oral doses of cyclophosphamide 2 mg/kg/d for 3 months. During treatment, the frequency of relapses, the mean dose of steroid and the complications of treatment were compared with a paired t-test, independent t-test, and chi-square test. Results: A significant decrease in the mean dose of steroids and the mean number of relapses were seen in patients after administration of rituximab and cyclophosphamide (P&lt;0.001). However, rituximab reduced the dose of steroid administration by 12.25 mg/d, while cyclophosphamide reduced only 2.83 mg/d (P&lt;0.001). Rituximab reduced the relapse rate two times on average, while cyclophosphamide reduced only 0.5 times (P&lt;0.001). The incidence of complications in the cyclophosphamide group was found to be more severe than the rituximab group. Conclusion: To compare rituximab versus cyclophosphamide regarding lower the frequency of recurrence after treatment, we found rituximab is a more suitable drug for the treatment of steroid-resistant NS than cyclophosphamide.

Efficacy and side effects of mycophenolate mofetil therapy in children with steroid dependent nephrotic syndrome in a tertiary paediatric nephrology centre in Sri Lanka

Background: Mycophenolate mofetil (MMF) has been shown to be a well-tolerated drug which could maintain prolonged remission in patients with steroid dependent nephrotic syndrome (SDNS). MMF is known to have a steroid sparing effect. Objectives: To determine the effect of MMF in reducing relapses in Sri Lankan children with SDNS and to ascertain the incidence of side effects of MMF in this population. Method: Children between 1-18 years of age with SDNS who had been treated with MMF for 12 months or more at the paediatric nephrology unit, Teaching Hospital Peradeniya, were selected and reviewed retrospectively. Children who had previously received immunosuppressive therapy other than prednisolone, cyclophosphamide, cyclosporin A, tacrolimus and levamisole and those who were on MMF for indications other than idiopathic nephrotic syndrome were excluded. Children and parents were interviewed and their patient-held health records, including their ‘nephrotic syndrome diary’ were reviewed. Data were collected twice a week using pretested questionnaires, in the nephrotic syndrome clinic for a period of 8 weeks. Results were analysed using SPSS version 23. Results:Thirty five children who met the selection criteria were included. Of them 26 (74.3%) were male and 09 (25.7%) were female. The median age was 9.7 years. Mean number of relapses in the year before starting MMF and the year after starting MMF were 3.5 and 1.8 respectively. The reduction in the relapse rate after being on MMF was significant (p=0.009). Child’s age or gender did not impact the relapse rate (p>0.05). The most common side effect observed was cough (20%) and the least common ones were abdominal pain, dyspnoea and dizziness (3%). Conclusions: In this study MMF reduced relapse rates of children with SDNS, despite some minor side effects.

The long-term outcome of childhood nephrotic syndrome in Germany: a cross-sectional study.

Long-term outcomes of children with nephrotic syndrome have not been well described in the literature. Cross-sectional study data analysis of n = 43 patients with steroid-sensitive (SSNS) and n = 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30years after onset, there was the longest follow-up period to date. The mean age at FUV was 33.6years (14.4-50.8 years, n = 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8years (1.2-14.5years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were "frequent relapsers" (25.6%) and four patients still had relapses beyond the age of 18years. Exceptof cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (< 4years) was a risk factor for frequent relapses. An early relapse (within 6months after onset) was a risk factor and a low birth weight was not a significant risk factor for a complicated NS course. The mean age of patients with SRNS at onset was 4.6 ± 4.4years and 27.5 ± 9.9years at FUV. Three patients received kidney transplantations. The positive long-term prognosis of SSNS can reduce the concern of parents about the probability of the child developing a chronic renal disease during the clinical course after onset.

Intravenous Immunoglobulin Treatment for Recurrent Optic Neuritis.

Recurrent optic neuritis neuritis (rON) is an autoimmune inflammatory condition of unknown cause. Intravenous immunoglobulin (IVIg) treatment is used for many autoimmune disorders; however we do not have any information about its effect in rON, other than case reports. We aimed to evaluate our patients with rON who were treated with IVIg. Data from all our patients with rON with or without anti aquaporin4 (AQP4) seropositivity, seen between April 2011 and October 2015, who received IVIg treatment were retrospectively evaluated. Nine patients (all female) with rON had received IVIg. These patients were aged between 34 and 65 years, and had started receiving monthly IVIg from 6 to 58 months after onset of disease. In three out of nine rON patients serum AQP4 antibody were positive. Under current treatments the patients had continued to have attacks, therefore monthly IVIg was given in addition to the existing immunosuppressant drug. The follow up duration was between 6 to 31 months. Three patients, each suffered one relapse under IVIg treatment. Mean number of relapses in the year prior to treatment was 1.4±0.72, whereas it was 0.3±0.5 during the year after IVIg therapy. During follow-up with IVIg administration only one patient had fever and no other adverse events were reported. Monthly IVIg is well-tolerated and safe and it seems to be effective in rON as an add on treatment. However, since our study is a retrospective case series, future randomized controlled trials with IVIg are needed.

Relapsing Thrombotic Thrombocytopenic Purpura: A Single Center Experience

Thrombotic thrombocytopenic purpura (TTP) is due to a severe deficiency of the von Willebrand factor (vWF) cleaving serine metalloprotease ADAMTS13 and is most commonly diagnosed in adults due to autoantibodies against ADAMTS13. Standard therapy includes plasma exchange (PEX) until platelet counts normalize plus concurrent high dose corticosteroids. In refractory cases, weekly pulse Rituximab for 4 doses is often added. Successful long-term management of relapsing patients beyond these treatments is unclear, in part because the mechanisms for relapsing TTP are unknown. Dysfunctional immunoregulatory systems likely play a role in relapsing disease. Several case series have described disease control following bortezomib therapy (Patriquin 2016). Other immunomodulators including complement pathway and tyrosine kinase inhibitors may prove to offer benefit. Further, supplementing PEX with N-acetylcysteine (Rottenstreich 2016) & Caplacizumab (anti-vWF humanized immunoglobulin) (Peyvandi 2016) has shown promising preliminary clinical results when used to treat an acute episode. Effects on relapse rates with these treatments have not been fully evaluated.Eight cases of relapsing TTP were identified at MedStar Georgetown University Hospital May 2004 to July 2016. Relapsing TTP was defined as recurrent episode(s) of thrombocytopenia, microangiopathic hemolysis, and confirmed ADAMTS13 activity levels <10% following remission from the initial TTP episode. Retrospective chart review was completed to evaluate demographic and clinicopathologic features, laboratories and treatment at relapse(s), and clinical outcomes.In our 8 patient cohort, 75% are female (6/8), 62.5% are African American (AA) (5/8), and the mean age at initial TTP diagnosis is 35.38 (range 16-67). The mean number of relapses is 3.38 (range 2-9) with a mean platelet nadir of 45,000/mcL. All patients remain alive. Two are ANA positive, 1 with known systemic lupus erythematosus (SLE) and 1 with suspected SLE. None are HIV positive, and none endorse a family history of TTP. Four identified infections as triggers for their TTP, 1 patient developed TTP during pregnancy and hormonal fertility treatments, and 3 had no identifiable triggers. All had an increased titer of ADAMTS13 inhibitor (Bethesda titer range 0.7 - >8) at the time of relapse(s). Normalization of ADAMTS13 activity was confirmed in most following treatment (n=6), with a mean ADAMTS13 activity level between relapses of 50.5% (range 32-88%). At the time of each relapse, all patients underwent daily PEX with fresh frozen plasma plus high dose corticosteroids for at least 5 days (range 5-21 days), with some requiring gradual PEX weaning over 1-4 weeks and steroid tapering over months based on lab parameters. Two relapsed quickly after PEX discontinuation, both in the setting of systemic illness (lupus flare, cholecystitis). Sequelae of TTP (neurologic, renal, hematologic anomalies) resolved with treatment. All patients received Rituximab therapy during the 1st or 2nd relapse. For the majority (87.5%, 7/8), this intervention did not lead to long-term remission, although 100% (2/2) who transitioned to prophylactic bolus Rituximab every 6 months post splenectomy achieved long-term disease control. It is difficult to distinguish whether remission resulted from maintenance Rituximab, the splenectomy, or a combination of the two. Patients who underwent splenectomy were vaccinated and have not had difficulty with infections or thrombosis.In conclusion, our cohort of patients with relapsing TTP all had documented ADAMTS13 inhibitors and acutely responded to daily PEX (most requiring PEX wean based on lab parameters) plus high dose corticosteroids. Although Rituximab therapy during initial relapse did not offer a high percentage of long-term remissions, the addition of prophylactic Rituximab every 6 months post splenectomy has achieved long-term control in 2 patients. In our cohort the majority are AA, suggesting genetic susceptibility. HLA/immune transcript levels and ribosomal gene signatures may correlate with TTP disease activity and risk for relapse (Edgar 2015), and could be used to identify high-risk patients in need of more intensive therapy. Given the complexity and severity of this disease, there is an ongoing need for evaluation of relapsing TTP and best strategies for long-term management. [Display omitted] DisclosuresKessler:Octapharma: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding; Grifols: Consultancy; Genentech: Consultancy, Research Funding; Biogen: Consultancy; Pfizer: Consultancy; Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; LFB: Other: Member of DSMB. Broome:True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

The Incidence and Differential Seasonal Patterns of Plasmodium vivax Primary Infections and Relapses in a Cohort of Children in Papua New Guinea

Plasmodium vivax has the ability to relapse from dormant parasites in the liver weeks or months after inoculation, causing further blood-stage infection and potential onward transmission. Estimates of the force of blood-stage infections arising from primary infections and relapses are important for designing intervention strategies. However, in endemic settings their relative contributions are unclear. Infections are frequently asymptomatic, many individuals harbor multiple infections, and while high-resolution genotyping of blood samples enables individual infections to be distinguished, primary infections and relapses cannot be identified. We develop a model and fit it to longitudinal genotyping data from children in Papua New Guinea to estimate the incidence and seasonality of P vivax primary infection and relapse. The children, aged one to three years at enrolment, were followed up over 16 months with routine surveys every two months. Blood samples were taken at the routine visits and at other times if the child was ill. Samples positive by microscopy or a molecular method for species detection were genotyped using high-resolution capillary electrophoresis for P vivax MS16 and msp1F3, and P falciparum msp2. The data were summarized as longitudinal patterns of success or failure to detect a genotype at each routine time-point (eg 001000001). We assume that the seasonality of P vivax primary infection is similar to that of P falciparum since they are transmitted by the same vectors and, because P falciparum does not have the ability to relapse, the seasonality can be estimated. Relapses occurring during the study period can be a consequence of infections occurring prior to the study: we assume that the seasonal pattern of primary infections repeats over time. We incorporate information from parasitological and entomology studies to gain leverage for estimating the parameters, and take imperfect detection into account. We estimate the force of P vivax primary infections to be 11.5 (10.5, 12.3) for a three-year old child per year and the mean number of relapses per infection to be 4.3 (4.0, 4.6) over 16 months. The peak incidence of relapses occurred in the two month interval following the peak interval for primary infections: the contribution to the force of blood-stage infection from relapses is between 71% and 90% depending on the season. Our estimates contribute to knowledge of the P vivax epidemiology and have implications for the timing of intervention strategies targeting different stages of the life cycle.