Reduction In Prednisone Dose Research Articles

Belimumab corticosteroid-sparing treatment in systemic lupus erythematosus: a real-life observational study (BESST study).

Data about the impact of Belimumab on corticosteroid sparing in real life are scarce. To assess the corticosteroid-sparing effect among patients with systemic lupus erythematosus (SLE) treated with Belimumab in real-life settings. Multicentric observational retrospective study including patients with SLE and having received Belimumab for at least 6months between 2011 and 2020, in eight French hospitals. "Low dose" referred to patients receiving up to 7.5mg of prednisone a day and "Very low dose" to those receiving strictly ≤ 5mg prednisone a day The primary endpoint was the reduction of daily prednisone dose after six months of Belimumab. The secondary endpoint was a change in the proportion of patients with low or very low dose of prednisone as well as those without prednisone during the Belimumab course. Censoring occurred for patients who stopped Belimumab. Bivariate analyses were performed using the Wilcoxon signed-rank test. The threshold for statistical significance was set at p < 0.05. Thirty patients were included. All were female with a median age of 38years. A significant reduction in prednisone dose was observed at month 6 (10 [7-20] vs 6.75 [2-9] mg, p < 0.0001), continued until month 12 (10 [7-20] mg vs 5 [0-7.12] mg, p < 0.001) and was sustained until month 24. The proportion of patients with very low dose of prednisone and those without prednisone progressively increased during the Belimumab course. Introducing Belimumab in patients with SLE, in real-life conditions, is associated with early and sustained corticosteroid-sparing effect.

Early effectiveness and safety analysis of belimumab in addition to standard treatment in patients with systemic lupus erythematosus.

This study aimed to evaluate the early effectiveness and safety of belimumab in addition to standard therapy in patients with systemic lupus erythematosus (SLE) for 24 weeks. This retrospective study was conducted with 60 adult patients with active SLE between June 2020 and August 2022. The patients either received intravenous belimumab in addition to standard therapy (n=31; 24 females, 7 males; mean age: 33.7±14.1 years; range, 18 to 52 years) or only standard therapy (n=29; 22 females, 7 males; mean age: 34.1±13.4 years; range, 19 to 66 years) for 24 weeks. Outcome measures, including safety and effectiveness (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI]), changes in biomarkers (double-stranded DNA [deoxyribonucleic acid]), serum complement levels, and immunoglobin G (IgG) were recorded. Adverse events were recorded. Baseline demographic and clinical characteristics were similar between the two groups. More patients in the belimumab group achieved a reduction of ≥4 points in SELENA-SLEDAI at weeks 12 and 24 (week 12, 77.4% vs. 41.4%, p=0.008; week 24, 87.1% vs. 48.3%, p=0.002). The mean score of SELENA-SLEDAI was significantly lower in the belimumab group compared to the standard therapy group at week 12. However, a significant difference was not reached at week 24. Moreover, mean levels of serum C3 and C4 in the belimumab group were significantly higher than those in the standard therapy group at weeks 12 and 24. A higher proportion of patients in the belimumab group had a normal C3 level than in the standard therapy group. In addition, belimumab treatment resulted in a significant decrease in IgG levels at both weeks 12 and 24. At week 24, the belimumab group had a higher reduction in prednisone dose than the standard therapy group. Furthermore, the percentages of patients with more than 50% reduction in prednisone over baseline were significantly greater for belimumab versus standard therapy at week 12 (p=0.002). The occurrence of adverse events was similar between the two groups (standard therapy group, 44.8%; belimumab group, 51.6%). Intravenous belimumab was well tolerated and significantly improved disease activity in Chinese patients with SLE at the early stage of treatment. More importantly, belimumab treatment could result in a rapid reduction in prednisone dose as early as week 12.

A Single-center, Real-world Experience of Chronic GVHD Treatment Using Ibrutinib, Imatinib, and Ruxolitinib and its Treatment Outcomes.

Chronic graft-versus-host disease (cGVHD) is a common cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Tyrosine kinase inhibitors (TKIs), including ruxolitinib, imatinib, and ibrutinib, have shown promising efficacy in cGVHD treatment. A total of 43 patients who developed cGVHD and received at least one line of TKI therapy for cGVHD treatment were evaluated retrospectively. The overall response, clinical benefit (CB), corticosteroid dose reduction, failure-free survival (FFS), and overall survival (OS) were assessed. A total of 62 lines of TKI therapy were evaluated, including ruxolitinib (n = 18), ibrutinib (n = 13), and imatinib (n = 31). With a 12-month median follow-up duration, 19/58 (32.8%), 20/41 (48.7%), and 17/29 (58.6%) responded to TKI therapy at 3, 6, and 12 months, respectively. The CB was observed in 80% of patients over time, allowing prednisone dose reduction in all 3 TKIs. The FFS rate at 12 months was higher in the imatinib (71%) and ruxolitinib groups (67%) than in the ibrutinib group (46%), while the OS rate at 12 months was similar among the three groups at 96%-100% in patients. In the sclerotic GVHD patient subgroup (n = 39), the overall response rate gradually increased over time. Ruxolitinib appeared to be as effective as imatinib and gradually improved the photographic range of motion score in sclerotic GVHD patients. TKI drugs ruxolitinib, imatinib, and Ibrutinib are effective and feasible for cGVHD treatment. Ruxolitinib is as effective as imatinib for sclerotic GVHD.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Hypersensitivity pneumonitis: Principles in diagnosis and management.

Efficacy and safety of belimumab treatment in childhood-onset systemic lupus erythematosus

Objective: To evaluate the efficacy and safety of belimumab in children with systemic lupus erythematosus (cSLE). Methods: The clinical data of 49 cSLE patients admitted into the Department of Rheumatology and Immunology, Children's Hospital affiliated to the Capital Institute of Pediatrics, from August 2018 to December 2021 were collected. They were divided into the belimumab treatment group (18 cases) and the traditional treatment group (31 cases) according to whether they received belimumab treatment. The cSLE patients in the traditional group had similar baseline SLEDAI scores with the belimumab group and were treated with traditional immunosuppressive drugs. The clinical symptoms and improvements before and after treatment, as well as the differences in adverse events during follow-up were compared between the two groups. Results: In belimumab group, the age was (11.9±1.8) years old, the median (Q1, Q3) of disease duration was 7.5 (2.0, 16.8) months, 3 patients were male, and 15 patients completed 24 weeks of treatment. In the traditional treatment group, 31 patients with cSLE were enrolled, with an average age of (11.3±2.4) years, a median (Q1, Q3) of disease duration of 7.0 (2.5, 10.5) months, among whom 6 patients were male, and 25 patients completed 24 weeks of treatment. At baseline, the belimumab treatment group had a significantly lower oral prednisone dose than the conventional treatment group [(29.58±12.43) mg/d vs (38.20±14.11) mg/d, P=0.037]. After 24 weeks of treatment, the dosage of prednisone in both groups was reduced, and the dosage of prednisone in the belimumab group was (14.12±5.86) mg/d, which was lower than that in the traditional treatment group [(23.51±9.79) mg/d] (P=0.002). After 24 weeks of treatment, the levels of complement C3 and C4 increased, the dsDNA levels and SLEDAI score decreased in both groups (all P>0.05). The incidence of adverse events in belimumab group (3/15, 3 cases) was lower than that in traditional treatment group (32.0%, 8/25) (P>0.05). Conclusions: Belimumab in the treatment of cSLE can reduce the initial dose of prednisone and facilitate the reduction of prednisone dose, significantly improve the clinical symptoms and organ involvement, and reduce the disease activity. The incidence of adverse events was low during belimumab treatment.

Mepolizumab for Eosinophilic Granulomatosis With Polyangiitis: A European Multicenter Observational Study.

ObjectiveMepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort.MethodsWe included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015–2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations.ResultsTwo hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty‐five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty‐two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty‐four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44).ConclusionMepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

Methotrexate Use in Generalized Autoimmune Myasthenia Gravis: A Case series

Methotrexate (MTX) is an inexpensive and well-tolerated immunosuppressive medication that is used anecdotally in autoimmune myasthenia gravis (MG). However, the efficacy in MG is unclear at this time. This retrospective analysis describes six patients with acetylcholine receptor antibody positive MG who were treated with MTX and corticosteroids. The efficacy of MTX was measured by steroid-sparing effect and the Myasthenia Gravis Foundation of America (MGFA) classification. MTX initiation was associated with a reduction in prednisone dosage in all patients. Minimal manifestation status was reached at an average duration of 10 months in 5 patients. No patients were hospitalized for myasthenia gravis exacerbations. There were no major side effects experienced with MTX use. This retrospective analysis suggests that MTX is safe and probably efficacious as a corticosteroid-sparing agent in the management of MG.

Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study.

To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks. Of the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs. 56% on placebo. The study reached its futility endpoint (p=0.03) suggesting that the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified. While rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase-3 trial of mild-moderately symptomatic AChR-Ab+ gMG. This study provides Class I evidence that for mild-to-moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year. ClinicalTrials.gov Identifier: NCT02110706.

Update of Multicenter, Retrospective Evaluation of Overall Response and Failure Free Survival Following Ruxolitinib Therapy for Heavily Pre-Treated Chronic Gvhd Patients with Steroid-Failure: A Proposal of Risk Score Model for Failure-Free Survival

BackgroundThe REACH3 trial evaluating Ruxolitinib (RUX) treatment for steroid-refractory chronic GVHD concluded that RUX leads to significantly greater overall response and failure-free survival (FFS) than best available therapies (NEJM 2021). We reported a real-world experience of RUX in 47 chronic GVHD (cGVHD) patients, with 36% overall response rate (ORR) at 6 months (ASH 2020). The present study expanded this to 115 pts, evaluating ORR, FFS and overall survival (OS), and explored prognostic factors associated with clinical outcomes.Patients and methodsA total of 115 patients treated with RUX for cGVHD from 2016 to 2021 at 5 sites were evaluated retrospectively. Patients and disease characteristics are as follows: median age 57.5 years; males 67 (60%); organ involvement at the time of RUX: skin 75.7%, mouth 51.3%, eye 42.6%, gastrointestinal 19.1%, liver 39.1%, lung 31.3%, and musculoskeletal 38.3%. Out of 108 pts with available HCT-CI prior to HCT, 29 pts (26.9%) had HCT-CI score 3 or higher, while 79 (73.1%) had HCT-CI score 0-2.The ORR were assessed at months 3, 6 and 12, retrospectively. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to treatment. FFS and OS were calculated from the day of starting RUX therapy for cGVHD treatment.For risk factor analysis, logistic regression was adopted for ORR at 6 months, while Cox's proportional hazard model was implemented for FFS and OS at 12 months. The following variables were evaluated for risk factor analysis: GVHD-related factors (cGVHD severity, no. of organ involvement, prednisone dose or RUX dose at start, previous history of acute GVHD); host factors (age or performance status at RUX starts, sex, HCT-CI comorbidity score pre-HCT); transplant factors (conditioning intensity; donor type, HLA match, T-cell depletion). From those variables identified as significant in the multivariate analysis, a prognostic risk score was generated as the sum of adverse risk factor scores.ResultsA total of 115 pts had severe (n=69, 60%) or moderate grade (n=44, 38.3%) cGVHD except 2 (1.7%) who had mild grade cGVHD with high-risk features. The median number of organ involvement was 3 (range 1-7). 96 pts (84.2%) received RUX as 4 th line or beyond for cGVHD treatment. The previous treatments included mycophenolate mofetil (n=46, 40.0%), extracorporeal photopheres (n=45, 39.1%), Imatinib (n=13, 11.3%), and Ibrutinib (n=9, 7.8%). RUX was started at 10-20 mg daily as the initial dose, then maintained at 20mg daily in two divided doses on months 3, 6 and 12.With a median follow-up duration of 12 months, ORR was attained in 46.8%, 61.8% and 62.3% at 3, 6 and 12 months, similar to 49.7% ORR rate at 6 months in the REACH3 study. ORR in the range of 48.1-64.5% at 6 months was observed across all the organs involved. No difference in ORR was noted between steroid-resistant vs steroid-dependent cGVHD, or according to previous treatment with TKI drug for GVHD. For ORR, severe grade cGVHD showed a lower ORR rate at 46.8% at 6 months compared to those with moderate/mild grade cGVHD at 81.1% (p=0.001).In terms of prednisone dose reduction, by 12 months, more than half of pts (63.8%) could taper prednisone doses below 0.1mg/kg/day, while the proportion of pts on prednisone dose below 0.1mg/kg/day was 14.83%, 33.6%, 47.6%, and 63.8% at month 0, 3, 6 and 12, respectively.A total of 39 failures (33.4%) were noted, including resistance requiring switch to other therapy (n=17), NRM (n=14), relapse of primary disease (n=3) and intolerance (n=5). The FFS rate in the overall population was 64.6% (54.1-73.2), while the OS rate was 83.3% (74.4-89.4%) at 12 months.For FFS, two risk factors were identified for FFS (Figure): 1) Severe grade cGVHD at RUX start (p=0.008, HR 2.496 [1.229-5.072]); 2) HCT-CI comorbidity 3 or higher (p=0.001, HR 2.802 [1.493-5.259]). When a risk score model was generated, it stratified pts according to the FFS at 12 months (p=0.0001): 85.8% in score 0 (n=32); 58.7% in score 1 (n=57); and 36.8% in score 2 (n=19).Conclusion:Updated results confirm that RUX is an effective treatment option for cGVHD pts, even including heavily treated pts. Also, favorable response was observed across all organs involved with GVHD. Failure of RUX is associated with cGVHD severity and HCT-CI score. [Display omitted] DisclosuresWhite: Novartis: Honoraria. Elemary: Jazz, BMS, Abbvie, Novartis, Pfiz: Membership on an entity's Board of Directors or advisory committees; Pfizer, Janssen: Membership on an entity's Board of Directors or advisory committees. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Mattsson: MattssonAB medical: Current Employment, Current holder of individual stocks in a privately-held company. Kim: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Paladin: Consultancy, Honoraria, Research Funding; Bristol-Meier Squibb: Research Funding. OffLabel Disclosure:This presentation discusses the use of ruxolitinib for chronic GVHD. This indication is under FDA review.

Ruxolinitib As Salvage Therapy for Chronic Graft-Versus-Host Disease

Background:Chronic graft-versus-host disease (cGVHD) remains a common and potentially life-threatening complication after allogenic hematopoietic stem cell transplantation (HCT). Systemic corticosteroids are first-line therapy, however, they are often associated with inadequate responses and multiple side effects. There has been no single standard therapy for refractory cGVHD. Recently, ruxolitinib, a selective JAK1/2 inhibitor, has been suggested to have efficacy as salvage therapy in cGVHD. However, data are limited to a multi-center retrospective survey of 41 patients (Zeiser et al. Leukemia. 2015; 29(10):2062-8). Herein, we present a single-institution's experience with ruxolitinib as salvage therapy for management of refractory cGVHD.Methods:In this single-center, IRB-approved, retrospective analysis, the charts of 47 patients who received ruxolitinib as salvage therapy for cGVHD from March 2016 through December 2016 were reviewed. Clinical data were collected and analyzed at start of ruxolitinib treatment, 3 months-post, and 6 months-post to identify changes in prednisone dose, patient perceived improvement, physician perceived improvement, and incidence of adverse events including hospitalizations, documented infections, cytopenias, relapse, and death. In addition, we assessed for treatment failure-free survival (FFS) from the time of ruxolitinib to any of the following events: initiation of new cGVHD therapy, relapsed disease, patient death, or discontinuation of ruxolitinib.Results:The cohort consisted of 47 patients (median age = 51; range = 21 - 91; 21 females and 26 males) who received fully ablative (n=26) or reduced-intensity conditioning (n=18) followed by an allogeneic HCT from matched related donor (n=15), unrelated donor (n=13), or other donor sources (cord or haplo-identical donors: n=16) for their hematologic disorders. The median time from HCT to ruxolitinib initiation was 40.5 months (range: 3.8 to 267.2). Of the 47 patients in this cohort, 38 patients (80.9%) had sclerotic chronic graft versus host disease.The average dose of prednisone in evaluable patients was 11.1 mg/day (95% CI 6.9 - 15.3 mg/day) at time of ruxolitinib initiation, which decreased to 7.7 mg/day (95% CI 4.1 - 11.4 mg/day, p=0.043 by paired signed rank test, 30% reduction) at 3 months, and 5.6 mg/day (95% CI 3.2 - 8.0, p<0.001, 49% reduction) after 6 months of ruxolitinib therapy. There were 12 patients (36%) and 14 patients (42%) who experienced prednisone dose reduction at 3 & 6 months, respectively. Patient-reported subjective improvement was observed in 22 of 41 evaluable patients (53.7%) and 23 of 37 evaluable patients (62.2%) at 3 and 6 months, respectively. Physicians rated subjective improvement in 29 patients (70.7%) at 3 months and 25 patients (67.6%) at 6 months. Infections were documented in 25 patients (56.8%), of which 6 (12.8%) were considered life-threatening. Two patients (4.2%) with CMV viremia with no end-organ disease were identified. Significant cytopenias requiring ruxolitinib dose reduction or discontinuation were observed in 3 patients (7.0%). During the study period of 6 months, 18 patients (40.9%) required hospitalization at least once, and 6 patients (12.8%) died within first 6 months of ruxolitinib use. Treatment failure-free survival at 6 months was 68.1% (95%CI; 52.7% to 79.4%) with the failure events including death (n=6), relapse (n=2), addition of new therapy (n=2), and discontinuation of ruxolitinib for any reason other than resolution of cGVHD symptoms (n=6) (Figure 1).Conclusion:Ruxolitinib is associated with prednisone reduction after 3 and 6 months, self-/physician-reported improvements, and favorable FFS at 6 months in patients with steroid-refractory chronic GVHD. Prospective randomized trials are warranted to further define its therapeutic benefits and risks of cytopenia/infectious complications. [Display omitted] DisclosuresSalhotra:Kadmon: Consultancy.

Treatment With Tofacitinib in Refractory Psoriatic Arthritis: A National Multicenter Study of the First 87 Patients in Clinical Practice.

Tofacitinib (TOF) is the first Janus kinase (JAK) inhibitor approved for psoriatic arthritis (PsA). It has shown efficacy in patients refractory to anti-tumor necrosis factor-α in randomized controlled trials (RCTs). Our aim was to assess efficacy and safety of TOF in clinical practice. This was an observational, open-label multicenter study of PsA patients treated with TOF due to inefficacy or adverse events of previous therapies. Outcome variables were efficacy, corticosteroid dose-sparing effect, retention rate, and safety. A comparative study of clinical features between our cohort of patients and those from the OPAL Beyond trial was performed. There were 87 patients (28 women/59 men), with a mean age of 52.8 ± 11.4 years. All patients were refractory to biologic disease-modifying antirheumatic drugs (DMARDs) and/or to conventional synthetic DMARDs plus apremilast. TOF was started at 5 mg twice daily after a mean follow-up of 12.3 ± 9.3 years from PsA diagnosis. At first month, Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) decreased from median 4.8 (IQR 4.1-5.4) to 3.7 (IQR 2.8-4.7, P < 0.01), Disease Activity Index for Psoriatic Arthritis from median 28 (IQR 18.4-34.1) to 15.5 (IQR 10.1-25.7, P < 0.01), and C-reactive protein from median 1.9 (IQR 0.3-5.0) to 0.5 (IQR 0.1-2.2) mg/dL (P < 0.01). Also, TOF led to a significant reduction in prednisone dose. Mild adverse effects were reported in 21 patients (24.13%), mainly gastrointestinal symptoms. TOF retention rate at Month 6 was 77% (95% CI 65.2-86.3). Patients in clinical practice were older with longer disease duration and received biologic agents more commonly than those in the OPAL Beyond trial. Data from clinical practice confirm that TOF seems to be effective, rapid, and relatively safe in refractory PsA despite clinical differences with patients in RCTs.

Rituximab in Refractory Myasthenia Gravis: Experience in a Single Healthcare Center in Mexico.

Background: Ten to fifteen percent of patients with myasthenia gravis (MG) have treatment-refractory disease. In short series and case reports, rituximab has proven to be effective in refractory MG.Methods: A retrospective, longitudinal study was conducted. Recruitment was performed in an MG cohort from a single third-level healthcare center in Mexico. The selection included refractory MG patients that were treated with rituximab. Response after rituximab therapy was assessed with MG composite score (MGCS) and prednisone dose reduction at 6, 12, and 18 months after initiation. Wilcoxon signed-rank test was used to evaluate differences between related groups for non-continual variables. P<0.05 was considered statistically significant.Results: Ten patients (7%) fulfilled criteria for refractory MG, and eight of them were treated with rituximab. The mean age at MG diagnosis was 25.5 (±2) years, with a female predominance (75%). All our patients (100%) had positive acetylcholine receptor (AchR) antibodies. The median MG duration was six years (interquartile range [IQR] 4.2-6) before rituximab initiation. All patients were previously treated with azathioprine and 50% additionally with cyclophosphamide. The median prednisone doses before rituximab treatment and 18-month follow-up were 50 mg (IQR 30-50 mg) and 10 mg (IQR 0-20 mg), respectively (p=0.011). The median baseline MGCS and at 18-month follow-up were 19.5 (IQR 11-31) and 6 (IQR0-16), respectively (p = 0.012).Conclusion: Rituximab appears to be associated with clinical improvement and prednisone dose reduction in Latin-American patients diagnosed with anti-AchR MG. Our findings need to be interpreted in light of the limitations mentioned.

Effectiveness and safety of baricitinib in rheumatoid arthritis: a monocentric, longitudinal, real-life experience

Baricitinib is a Janus-kinase (JAK) 1/2 inhibitor, approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We report the first real-life experience with baricitinib in a monocentric cohort of unselected RA patients. We enrolled consecutive RA patients starting baricitinib. At baseline and after 4, 12, 24 and 48 weeks we assessed the disease activity by composite indices (SDAI, CDAI and DAS28CRP) and ultrasonography, and we recorded any adverse events. The primary endpoint was the percentage of patients achieving SDAI remission at week 4. We enrolled 59 patients [(F:M = 50:9, median age 58.1 years (IQR 12.8), median disease duration 144 (IQR 150) months] treated with baricitinib in combination with a csDMARD (52.5%) or monotherapy (47.5%) for a median follow-up of 24 weeks (IQR 36). The 12-month drug retention rate was 74%. At weeks 4, 12, 24 and 48 we observed a significant reduction of DAS28, CDAI and SDAI, global health and pain (p<0.001 for all). After 4 weeks of treatment, 12% of patients achieved SDAI remission. Concomitant csDMARDs, previous biological DMARDs, gender, seropositivity and BMI did not affect the efficacy of baricitinib. Baricitinib allowed a significant reduction in prednisone dose after 12 and 24 weeks and a rapid and sustained ultrasound improvement. No serious adverse events, serious infections or cardiovascular events were recorded. Our study confirms the efficacy and safety profile and rapid onset of the effect of baricitinib in RA patients in a real-life setting.

Exacerbation Rate in Generalized Myasthenia Gravis and Its Predictors

Objective: The aim of the study was to estimate the exacerbation incidence rate (IR) in acetylcholine receptor antibody (AChR)-positive generalized myasthenia gravis (MG) and its predictors. Methods: The primary outcome in this retrospective study was to estimate moderate-to-severe (M-S) exacerbations IR in the early course of generalized MG. The secondary outcome was to explore the predictors of MG exacerbations. Results: Between 1999 and 2015, we identified 78 AChR-positive generalized MG patients and 37 M-S exacerbations over the first 6 years following the onset of generalized MG symptoms. The M-S exacerbation IR was 12.2 per 100 person years (95% confidence interval [CI] 8.8–16.8). Any exacerbation (including mild) IR was 24.4 per 100 person years (95% CI 19.4–30.7). After controlling for confounding factors, MG exacerbation IR predictors included gender, disease severity at onset, and prednisone dose reduction with risk ratio of 0.34 (male gender), 2.67, and 20.8, respectively (all p values <0.05). M-S exacerbation occurred in 25 cases (32.1%), while any exacerbation (mild or M-S) was detected in 45 cases (57.7%). Conclusion: More than half of newly diagnosed AChR + MG cases experience an exacerbation in the first 6 years. Gender, disease severity at onset and prednisone dose reduction are predictors that could inform clinical practice and future research.

Salvage Therapy with Low-Dose Ruxolitinib Led to a Significant Improvement in Bronchiolitis Obliterans Syndrome in Patients with cGvHD after Allogeneic Hematopoietic Stem Cell Transplantation

Background Bronchiolitis obliterans syndrome (BOS) is a life-threatening pulmonary manifestation of chronic graft versus host disease (cGVHD) post-allogeneic hematopoietic stem cell transplantation (HSCT), without a clear standard of care. Systemic corticosteroids remain the backbone of therapy for BOS, but their side effect profile makes them disadvantageous for prolonged use. Ruxolitinib (RUXO), a Janus-associated kinase (JAK) 1/2 inhibitor approved for the treatment of patients with intermediate-2 or high-risk primary myelofibrosis,has shown excellent response rates in steroid-refractory/intolerant cGVHD. This study seeks to investigate the efficacy of ruxolitinib on steroid-refractory BOS, and additionally, determine the efficacy of ruxolitinib in these patients and the clinical factors affecting the response to ruxolitinib. Method This study involved adult patients suffering BOS after an allogeneic HSCT for a hematological malignancy between January 2014 and June 2018 at the First Affiliated Hospital of Zhejiang University School of Medicine and Ningbo Hospital of Zhejiang. Univariable analyses for treatment response risk factors were performed using the Fisher exact test and chi-square test. Logistic regression analysis was used to perform multivariable analysis to calculate the hazard ratio (HR) with a 95% confidence interval (CI). Overall survival (OS) was defined as the time from stem cell infusion to death from any cause and calculated by the Kaplan-Meier method. Results Twenty-five patients were retrospectively enrolled in this analysis and patient characteristics were shown in Table 1. At the time of BOS diagnosis, most patients presented with moderate or severe obstruction. Besides, all patients had worsening lung function or worsening clinical symptoms under systemic prednisone treatment. After a median duration of RUXO therapy of 8.5 (1.5-20) months, the overall response rate was 68.0%: two patients (8.0%) achieved complete remission, and 15 (60.0%) achieved partial remission. The median time from initiation of RUXO to achieve the best responses was 3 months (range, 1.5-8). Since initiating RUXO, predicted forced expiratory volume in 1 s (FEV1) % increased after 3 months and 6 months compared with measurements before RUXO in responders. Of note, an average reduction in prednisone dose of 39.3% after 3 months of ruxolitinib therapy and 59.5% after 6 months of ruxolitinib therapy was reported. Only FEV1 mild decline before ruxolitinib with a ratio ≤15% was an independent predictor to achieve a response to RUXO (HR = 0.063, 95% CI 0.006-0.624, P = 0.018). As for safety profile, hematological adverse effect included that two patients harboring cytopenia with grade 2-3. Regarding the nonhematological toxicities, two patients developed grade 3 hypertriglyceridemia. Referring to infection events, 11 patients (44%) had a severe pulmonary infection of ≥3 grade. Of note, cytomegalovirus (CMV) DNAemia was observed in 3 patients (12%) and Epstein-Barr virus (EBV) DNAemia was observed in 10 patients (40%). Following a median follow-up of 255 days after RUXO, the 2-year incidence of nonrelapse mortality and 2-year overall survival rate after RUXO among patients with BOS was 27.8% and 62.6%, respectively. Conclusion The present study showed that in heavily pretreated patients with BOS, ruxolitinib induced a relatively high response, leading to an increased 2-year OS rate in patients with BOS. Although a small number of subjects and a retrospective nonrandomized design of this study might make a bias, our data still indicated RUXO as a promising treatment option to improve the prognosis of post-HSCT BOS, with pulmonary function stabilization or even improvement and steroid sparing. Also, the substantial clinical benefits and efficacy of ruxolitinib on BOS need to be balanced against infection risks. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ruxolitinib (RUX, Jakafi, Novartis, Basel, Switzerland)

Multicenter, Retrospective Evaluation of Therapeutic Efficacy of Ruxolitinib for Chronic Gvhd Treatment

Background Several agents have been investigated for beyond second-line treatment of chronic graft-versus-host disease (GVHD). Ruxolitinib has been recently approved for steroid-refractory acute GVHD, while a prospective randomized study is ongoing to examine its efficacy in steroid-resistant chronic GVHD (cGVHD). The present study evaluated the efficacy of Ruxolitinib in terms of 1) overall response rate (ORR), 2) clinical benefit (CB), 3) dose reduction of corticosteroid exposure, 4) failure-free survival (FFS) and 5) overall survival (OS), in patients heavily pretreated for steroid-resistant cGVHD. Patients and methods A total of 47 patients who developed cGVHD after HCT and treated with Ruxolitinib for cGVHD from March 2016 to April 2020, at three different sites (Princess Margaret Cancer Center, Canada; Vancouver General Hospital, Canada and Saint Vincent Hospital, Australia), were evaluated in the retrospective study. Patients and disease characteristics are as follows: median age 52 years; classical 35 (71%), overlap syndrome 14 (29%). Of note, 27 patients (57.4%) had a previous history of acute GVHD. The ORR and CB were assessed at months 3, 6 and 12, retrospectively. Responses were evaluated according to NIH scoring/staging/response assessment as part of standard clinical practice. CB was assessed considering clinical response as well as steroid dose reduction. For systemic steroid dose reduction, prednisone dose per kg per day was captured prior to Ruxolitinib start, at months 3, 6 and 12. Treatment failure was defined as 1) resistance requiring treatment switch, 2) non-relapse mortality (NRM), 3) relapse, 4) intolerance to treatment. FFS and OS were calculated from the day of starting Ruxolitinib therapy for cGVHD treatment. Results A total of 47 patients had moderate (11/47, 24.4%) to severe (33/47, 73.3%) cGVHD except one who had mild grade cGVHD with a high-risk feature (thrombocytopenia at the time of Ruxolitinib start). The median number of organ involvement was 3 (range 1-7). Over half of patients (63.8%) received Ruxolitinib as 4th line or beyond for cGVHD treatment, while median number of previous lines of therapy was 3 (range 1-9). All 47 patients (100%) had been previously treated with systemic steroids; other previous treatments included ECP therapy (53.2%), Imatinib (29.8%), Ibrutinib (23.4%), Rituximab (21.3%). Ruxolitinib was started at 10-15 mg daily as initial dose, then maintained at 20mg daily in two divided doses on months 3, 6 and 12.With a median follow-up duration of 12 months, ORR was attained in 35.7%, 36.0% and 35.0% at 3, 6 and 12 months, respectively (Figure A). Of note, ORR in patients with sclerotic changes was 56%, and 61.5% in those with lung involvement. Patients resistant to TKI (i.e. Imatinib or Ibrutinib) for cGVHD treatment showed similar ORR compared to those naïve to TKI therapy.The CB was observed in 53.5%, 66.7% and 72.2% at months 3, 6 and 12, respectively (Figure B). Patients resistant to TKI for cGVHD treatment did not show any difference in CB compared to those naïve to TKI therapy.In terms of prednisone dose reduction, by 12 months , half of patients (50.0%) could taper prednisone doses below 0.1mg/kg/day, while the proportion of patients on prednisone dose below 0.1mg/kg/day was 9.3%, 20.0%, 17.4%, and 50.0% at month 0, 3, 6 and 12, respectively (Figure C). The group who achieved CB at 3 months showed a significantly lower dose of prednisone at 12 months (0.078mg/kg/day) compared to those without clinical benefit at 3 months (0.197mg/kg/day; p=0.033; Figure D).Out of 37 patients evaluated, 11 failures (29.7%) were noted, including resistance requiring a switch to other therapy (n=7), NRM (n=2) and intolerance (n=2). The FFS rate at 1 year in the overall population was 68.5% (Figure E). The FFS at 1 year in those having CB at 3 months vs not was 86.5% vs 51.4% (p=0.025).The OS at 1 year was 90.9% (Figure F). The OS at 1 year in those having a CB at 3 months vs not was 100% vs 78.8% (p=0.053). Conclusion: This multicenter retrospective study revealed that Ruxolitinib is an effective treatment option for patients with cGVHD, with good ORR and CB. The achievement of CB in the first 3 months correlated well with steroid dose reduction. It suggests that Ruxolitinib is a feasible GVHD treatment option, even for patients who were heavily pretreated for cGVHD or failed previous TKI drug. Figure 1 Disclosures Hamad: Abbvie: Honoraria; Novartis: Honoraria. OffLabel Disclosure: Ruxolitinib treatment for steroid resistant chronic GVHD

Rest or Exercise (RESTOREX) in Myasthenia Gravis: A Randomized Controlled Trial

Background: In Myasthenia Gravis (MG), the effect of exercise is not well documented in controlled trial. In the present study, the efficacy and safety of exercise in MG in comparison to rest is presented. Methods: In this single-center open-labeled randomized clinical trial the patients were randomized in 1:1 ratio to exercise (30 min walk) or rest arm in addition to standard treatment of MG. The Primary endpoint was 50% change in Myasthenia Gravis Quality of Life (MG-QOL15) at 3 months and secondary endpoints were change in Myasthenic Muscle Score (MMS), Myasthenia Gravis Activities of Daily Living (MGADL), grip strength, AChEI and prednisone dose, 6 minute walk test (6MWT), decrement in trapezius muscle and adverse events at 3 months. The Outcome was defined at three months by 50% change compared to the baseline parameters. Results: There were 20 patients in each arm which were matched for demographic and clinical parameters. The patients in exercise arm had significantly better QOL as evidenced by 50% improvement in MG-QOL15 (P = 0.02), increase in number of steps (P = 0.03) and the distance covered in 6MWT (P = 0.003). The scores of MG-QOL15 (P = 0.03), MMS (P = 0.048), and distance travelled (P <0.001) also revealed significant group difference. Intragroup comparison revealed that both exercise and rest arm significantly improvement with respect to MG-QOL15 in exercise (P = 0.001) and rest (P = 0.001), MMS in exercise (P = 0.001) and rest (P = 0.001), reduction in pyridostigmine (P = 0.03) and prednisone (P =0.001) dose in exercise, increase in number of steps in exercise (P =0.001) and increase in walking distance in 6MWT in both exercise (P =0.001) and rest arm (P = 0.023). There was no adverse event in any group. Interpretations: The study provides class II evidence of improved quality of life in mild to moderate MG by 30 min walk in comparison to rest. Trial Registration: The trial was registered in Clinical Trial Registry of India (CTRI/2019/11/021869). Funding Statement: World Congress of Neurology, the authors received no funding for this study. Declaration of Interests: All authors declare no competing interest. Ethics Approval Statement: This study was approved by Institutional Ethics committee (PGI/BE/632/2018), SGPGIMS, Lucknow.

Infliximab for the treatment of refractory polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a necrotizing vasculitis predominantly affecting medium and small size arteries. Cyclophosphamide, a drug with narrow therapeutic range and poor safety profile, constitutes the treatment of choice for PAN vasculitis with major organ involvement. To describe our clinical experience in treating refractory PAN with infliximab (a TNF inhibitor), a drug with good tolerability and better safety profile than cyclophosphamide. Twenty-six PAN patients were admitted to our rheumatology unit between 2006 and 2017, of whom nine patients, with severe and refractory disease, were treated with infliximab after failure of standard treatment. We describe herein the patients' characteristics, clinical manifestations, severity and response to infliximab treatment and review the current literature. Complete remission was defined as the absence of features of active disease and withdrawal of prednisone therapy. Significant improvement was defined as clinical improvement and prednisone dose reduction of at least 50% or a 50% reduction in immune modulatory medications other than prednisone. After 4months of treatment, 8/9 (89%) patients achieved significant improvement, with two of them achieving complete remission. We suggest that anti-TNF agents, and in particular infliximab, are relatively safe and efficacious treatment options in refractory PAN. A randomized controlled trial should be done in order to objectively evaluate infliximab in PAN.

Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (cGVHD) continues to be a major complication after allogeneic hematopoietic cell transplantation, significantly affecting patients' quality of life. A regimen of systemic corticosteroids is considered first-line therapy but is often associated with inadequate responses and multiple side effects. In patients with refractory disease, an evidenced-based consensus is lacking as to the single best approach to managing symptoms. Ruxolitinib, a selective JAK1/2 inhibitor, has recently gained favor as a second-line approach in patients with steroid-refractory cGVHD. In this retrospective study, we evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between March 2016 and December 2017 at our institution, and evaluated ruxolitinib's impact at 6 and 12 months, based on the National Institutes of Health Severity Scale, including organ-specific responses, and mean prednisone dose. Furthermore, we present the first reported probability of ruxolitinib's treatment failure-free survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy, complete response, partial response, and stable disease was observed in 13% (n = 6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year probability of FFS was 54.2% (95% confidence interval, .388 to .673), and ruxolitinib use was associated with a reduction in prednisone dose. In conclusion, our data, which represent the largest cohort of patients with cGVHD reported to date, support the use of ruxolitinib for cGVHD refractory to steroids and currently available salvage therapies, discontinued due to lack of response and high cost.

Eosinophilic cystitis in children: A case report.

The aim of the present case report was to investigate the clinical features, pathological examination and treatment of eosinophilic cystitis (EC) in children. Two cases of EC were reported and reviewed from January 2016 to March 2017. Case 1 (male; 6 years old) had intermittent hematuria, frequent urination, urgent urination, difficulty in urination and abdominal pain. Case 2 (male; 7 years old) had frequent urination, urgent urination, urinary pain, dysuria and suprapubic pain with no hematuria. One patient had a history of allergies and both patients underwent a cystoscope biopsy. Blood eosinophils were clearly increased and a bone marrow biopsy examination revealed that marrow eosinophils were also increased in both cases. The urine culture results were negative. Ultrasonography and computed tomography revealed uneven thickening of the bladder wall and diffusive mucosal lesions. Cystoscopy revealed that the bladder volume became smaller and the mucosa at the bladder floor and neck was red. Lesions were biopsied through the urethra and the following characteristics were observed: Congestion and edema of the bladder mucosa, infiltration of the blood vessels and eosinophils in the muscular layer, accompanied by focal muscle necrosis. Patient 1 was administered anti-inflammatory and cetirizine hydrochloride treatments, followed by 6 weeks of prednisone dose-reduction therapy. Patient 2 was administered antibiotics and cetirizine hydrochloride. Following 6-month follow-ups, abnormal voiding symptoms had disappeared in each case. Ultrasonography and computed tomography revealed no bladder wall thickening or space-occupying lesions. EC in children is rare and easily misdiagnosed as nonspecific bladder inflammation or bladder occupying lesions. Cystoscopy and biopsy are necessary to diagnose EC and conservative treatments with anti-inflammatory, anti-allergic and cortical hormone nonspecific treatments are suggested.