Steroid Reduction Research Articles

REducing STEroids in Relapsing Nephrotic syndrome: the RESTERN study— protocol of a national, double-blind, randomised, placebo-controlled, non-inferiority intervention study

IntroductionOral corticosteroids are the first-line treatment for idiopathic childhood nephrotic syndrome. Most children experience several relapses, needing repeated courses of corticosteroid therapy. This exposes them to side effects and long-term...

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations \u2013 The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol

BackgroundThe most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects.Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.MethodsThis is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.DiscussionThis will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.Trial registrationClinicaltrials.gov, NCT02857842, 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.

Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic melanoma.

e21052 Background: Non immediate allergic reactions (niAR) related with oncology drugs are a rare entity. Usually, it is called Drug Reaction with eosinophilia and sistemic symptoms (“DRESS”), occurring at first ten days of treatment.Recently, the treatment of metastatic melanoma (MM) has included new drugs in patients wtih BRAF V600E mutation. Despite skin reactions are usual, niAR to these drugs have not been reported. We present 2 clinical cases with mm treated with BRAFi, developing such niAR. Methods: Patient 1: 47yo female with lymph node relapse and multiple subcutaneous skin metastases (previously pT1N0M0 melanoma) that received nivolumab in adjuvant setting. BRAF-mutated. She starts with Vemurafenib-Cobimetinib (V-C). At 8 days, niAR (maculo-papular exantema G4, fever G2). After discontinuation of this treatment (3 weeks), it is changed to Dabrafenib(50%)-Trametinib (D-T). With only 1 dose, skin niAR (G3) is newly developed. Biopsy are taken at the beginning (T0), during (T1) and after desentizitation (T2). Patient 2: 60 yo female, lung and lymph node relapse of melanoma (previously pT2bN0M0) after IFN-alpha adjuvant 2 years before. BRAF-mutated. Start with V-C. At 9 days, skin niAR (G4), with fever (G1). Discontinuation of treatment. Biopsys and blood test are taken (T0, T1 and T2). Gene expression was performed with PanCancer Immune Profiling Panel Nanostring™ in this points. Results: Different lymphocytic subpopulations in blood and biopsy at acute phase are showed in table 1. Immune gene expression profiling found decreased expression of 5 genes: UBC, IL8, IL32, NFKB1A and FOS, increasing IFNGR1 (pt 1). In both of pts, desensitizitation protocol by Allergologists was made succesfully, with incremental oncology drugs and steroid reduction protocol. Both of pts had a maior partial response (RECIST), even the scarce of the drug received. Conclusions: D and V develop important “of class” skin niAR. Different immunologic patterns are related with this niAR. Previous exposition to IFN or anti-PD1 therapy might modulate such response. Immune gene expression profiling could be used as a method to identify biomarkers. Desensitization with BRAFi has enough efficacy and tolerance.

Effectiveness and safety of infliximab biosimilar CT-P13 in treating ulcerative colitis: a real‑life experience in IBD primary centers

The aim of this study was to assess the efficacy and safety of infliximab biosimilar (IFX) IFX CT-P13 in inducing and maintaining remission in ulcerative colitis (UC) outpatients in Italian primary gastroenterology centers. Patients were prospectively assessed at entry, after 8, 12, 24, 36, and therefore 52 weeks. Clinical activity was rated as per the Mayo Score. The primary endpoint was reaching of clinical remission (Mayo Score ≤2). Several secondary endpoints were clinical response to treatment, reaching of mucosal healing (MH), safety of the drug. Twenty-nine patients (16 males and 13 females, mean age 45 years, range 35-42 years) were enrolled. Eleven (37.9%) patients had previous exposure to other anti-TNF-α. Clinical remission was present in 78.5% at week 24, and in 100% at 12-month follow-up. Subgroup analysis did not reveal significant differences in clinical remission between IFX-naïve patients and patients switching from originator to IFX biosimilar. A clinical response was observed in 92.3% at week 8, in 50.0% at week 16, in 100% at week 36 and in 100% at 12-month follow-up. MH occurred in 85.7% at week 24, and in 100% at 12-month follow-up Reduction of steroids was achieved in 92.3% at week 8, and in 100% during follow-up. One patient underwent proctocolectomy 3 weeks after starting IFX CT-P13. The median C-reactive protein and calprotectin levels during follow-up were significantly reduced during follow-up. No adverse events were observed during follow-up. IFX CT-P13 seems to be very effective and safe in real-life experience at primary IBD centers.

The Burden of Respiratory Disease in Very-Low-Birth-Weight Infants: Changes in Perinatal Care and Outcomes in a Decade in Spain

Background: Advances in perinatal care have led to a significant reduction in morbidity and mortality among very-low-birth-weight (VLBW) infants. Much of this progress is related to the prevention and management of respiratory disease. Objectives: To evaluate changes in perinatal care and its influence on respiratory morbidity and mortality among VLBW infants in Spain in 2 consecutive periods (2002-2006 and 2007-2011). Methods: This is a retrospective analysis of data prospectively collected of all VLBW infants included in the Spanish SEN1500 network. Patients with major congenital anomalies, those who died in the delivery room (DR) and infants <23⁰ or >34⁶ weeks of gestational age (GA) were excluded. Results: During the study period, out of 27,205 eligible VLBW infants, 24,598 (90.4%) met inclusion criteria. The most striking and statistically significant results found in the second period were: (i) reduction in the proportion of “outborn” patients; (ii) an increase in prenatal steroid administration; (iii) enhanced non-invasive respiratory support in the DR and NICU; (iv) reduction in invasive mechanical ventilation, surfactant administration, and steroids for bronchopulmonary dysplasia (BPD). Moreover, survival to hospital discharge increased (83.5 vs. 84.7%; p = 0.015); however, survival without BPD increased only among the most immature (23⁰ to 26⁶ weeks' GA) from 26.6 to 31.6% (p < 0.001). Conclusions: Enhanced adherence to international recommendations in perinatal care and a significant reduction in mortality were found during the second period. Survival without BPD increased only among the most immature. Further investigation is needed to optimize the strategies to prevent and manage respiratory disease in this group of patients.

AKR1C3 Inhibitory Potency of Naturally-occurring Amaryllidaceae Alkaloids of Different Structural Types

Aldo-keto reductase 103 (AKRIC3) is an important human enzyme that participates in the reduction of steroids and prostaglandins, which leads to proliferative signaling. AKRIC3 is frequently upregulated in various cancers, and this enzyme has been suggested as a therapeutic target for the treatment of these pathological conditions. The fact that the isoquinoline alkaloid stylopine has been identified as a potent AKRIC3 inhibitor has prompted us to screen a library of diverse types of Amaryllidaceae alkaloids, which biogenetically are isoquinoline alkaloids, on a recombinant form of AKRIC3. From the tested compounds, only tazettine showed moderate AKRIC3 inhibitory potency with an IC5o value of 15.8 ? 1.2 pM. Tazettine is a common Amaryllidaceac alkaloid, which could be used as a model substance for the further development of either analogues or related compounds with better inhibition potency.

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed “long-interval cytapheresis (LI-CAP)”, in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

Metabolic dysfunction in female mice with disruption of 5α-reductase 1.

5α-Reductases irreversibly catalyse A-ring reduction of pregnene steroids, including glucocorticoids and androgens. Genetic disruption of 5α-reductase 1 in male mice impairs glucocorticoid clearance and predisposes to glucose intolerance and hepatic steatosis upon metabolic challenge. However, it is unclear whether this is driven by changes in androgen and/or glucocorticoid action. Female mice with transgenic disruption of 5α-reductase 1 (5αR1-KO) were studied, representing a ‘low androgen’ state. Glucocorticoid clearance and stress responses were studied in mice aged 6 months. Metabolism was assessed in mice on normal chow (aged 6 and 12 m) and also in a separate cohort following 1-month high-fat diet (aged 3 m). Female 5αR1-KO mice had adrenal suppression (44% lower AUC corticosterone after stress), and upon corticosterone infusion, accumulated hepatic glucocorticoids (~27% increased corticosterone). Female 5αR1-KO mice aged 6 m fed normal chow demonstrated insulin resistance (~35% increased area under curve (AUC) for insulin upon glucose tolerance testing) and hepatic steatosis (~33% increased hepatic triglycerides) compared with controls. This progressed to obesity (~12% increased body weight) and sustained insulin resistance (~38% increased AUC insulin) by age 12 m. Hepatic transcript profiles supported impaired lipid β-oxidation and increased triglyceride storage. Female 5αR1-KO mice were also predisposed to develop high-fat diet-induced insulin resistance. Exaggerated predisposition to metabolic disorders in female mice, compared with that seen in male mice, after disruption of 5αR1 suggests phenotypic changes may be underpinned by altered metabolism of glucocorticoids rather than androgens.

Vedolizumab in Inflammatory Bowel Disease: A Retrospective Review of Clinical Efficacy, Extraintestinal Manifestations and Adverse Reactions

Introduction: Vedolizumab is a humanized monoclonal antibody with gut-specific anti-inflammatory activity for treatment of moderate to severe ulcerative colitis (UC) or Crohn disease (CD). We describe our experience with vedolizumab in a real-world clinical setting. Methods: A retrospective review of patients with UC and CD treated with vedolizumab was performed over 16 months. Patients that completed induction at weeks 0, 2, and 6 and with adequate clinical follow up were included. Response to treatment was assessed using the Harvey Bradshaw Index (HBI) and partial Mayo Score (pMS) for CD and UC, respectively. Analysis included prednisone dose reduction, use of combination therapy, adverse reactions, and extra-intestinal manifestations (EIM). Results: Our study included 40 patients (25 CD, 15 UC). In the CD group, mean HBI at week 0 was 8.6 (sd 4.1, n=25), at week 8 was 6.1 (sd 3.5, n=25), and at week 24 was 5.4 (sd 3.6, n=23). Mean prednisone dose at week 0 was 20.4 (sd 19.5, n=25); at week 24 was 9.0 (sd 14.8, n=23). 18/25 (72%) of CD patients were on maintenance therapy beyond 24 weeks, mean 41.4 (24-70). 11/18 (61%) were on combination therapy, 5/11 (45%) required more frequent vedolizumab dosing. 7/25 (28%) were considered treatment failures (2/7 surgery, 5/7 alternate therapy). In the UC group, mean pMS at week 0 was 5.8 (sd 1.6, n=15), week 8 was 3.6 (sd 2.4, n=15), and week 24 was 2.5 (sd 1.9, n=13). Mean prednisone dose at week 0 was 10.0mg (sd 14.1); at week 24 was 5.7mg (sd 14.0). 10/15 (67%) were on maintenance therapy beyond 24 weeks, mean 41.6 (24-68). 5/10 (50%) were on combination therapy with 1/5 requiring q4 week dosing. 5/15 (33%) were considered treatment failures (3/5 colectomy, 2/5 alternate therapy). 11/40 patients reported EIM. 8/11 had improvement (arthralgia=6, erythema nodosum (EN)=2, aphthous ulcers=1). In 3/11, EIM did not improve (pyoderma gangrenosum (PG)=3). 3/11 with EIM were considered treatment failures (aphthous ulcers=1, PG=1, arthralgia= 1). Adverse reactions occurred in 7/40 patients (arthralgia=3, fatigue=1, headache=2, pruritus=1, URI=2). 1/7 required stopping therapy. Conclusion: Vedolizumab achieves clinical response and steroid reduction in a majority of patients with moderate to severe IBD. Strategies to improve response include combination therapy and shorter dosing intervals. The majority of EIM were controlled, though PG failed to improve in 3/3 patients. Vedolizumab is well tolerated with 1/40 patients stopping therapy due to adverse reactions.

Temozolomide low-dose chemotherapy in newly diagnosed low-grade gliomas: activity, safety, and long-term follow-up.

To explore the efficacy and toxicity of an extended schedule of temozolomide (50 mg/mq 1 week on/1 week off) in a population of newly diagnosed low-grade gliomas (LGG). Primary endpoints were progression-free survival (PFS) at 12 and 24 months and response rate evaluated with Response Assessment in Neuro-Oncology Criteria. Secondary endpoints were clinical benefit (reduction of seizures frequency), reduction of steroid, and modifications of Karnofsky Performance Status. From 2006 to 2009, we enrolled 14 consecutive patients with newly diagnosed LGG: 8 grade II astrocytomas, 2 oligodendroglioma, and 4 oligo-astrocytoma. Temozolomide was administered for 18 cycles (mean) per patient (range 3-24 cycles). In 57.5% (n = 8), we observed stable disease, 28.5% (n = 4) presented a minor response, and 14% (n = 2) showed progression. Five patients presented early progression during the first year of treatment and the study was stopped. A relevant clinical benefit was observed in 85% of patients (seizure control). After 6 years of follow-up, only 4 patients died. Prolonged PFS was associated with 1p-19q codeletion over 1p-19q intact (35 vs 4 months; p<0.04) and IDH1 mutation over IDH1 wild-type (36 vs 6 months; p<0.009). The study was interrupted for the high rate of progression observed in the first 14 patients enrolled. However, our results show that an extended low dose of temozolomide presents interesting activity with objective response and clinical benefit, but does not seem to prevent progression in patients presenting unfavorable molecular prognostic factors.

P08.62 Salvage chemotherapy with bevacizumab and fotemustine in temozolomide-pretreated patients with recurrent grade III gliomas: a phase II study

AbstractIntroduction:Fotemustine is a nitrosourea with elevated lipophilic properties, that has shown activity as monotherapy in recurrent grade III gliomas, but few data are available on the association with the antiangiogenic drug bevacizumab.Method:From July 2008 to November 2015 we accrued, in this single arm phase II study, patients with an histological diagnosis of grade III glioma (according to WHO, 2007) at relapse after radiotherapy and/or temozolomide and we treated them with a combination of bevacizumab and fotemustine. The primary endpoint was 6-month progression-free survival (PFS-6), while secondary endpoints were overall survival (OS), disease control rate and toxicity.Results:Forty-six patients with grade III glioma (22 astrocytomas, 10 oligodendrogliomas and 14 oligoastrocytomas, 67% MGMT methylated and 30% 1p/19q codeleted) were enrolled. Median age was 45 years and KPS ≥ 90 in 54%. PFS-6, median PFS and OS were 45%, 5 months and 9 months, respectively. Nineteen patients (41%) had already received prior chemotherapy lines and 35% a second surgery before inclusion into the trial. We observed a 95% disease control rate (response or stable disease on MRI) after the induction phase with a neurological improvement in 40% and steroid reduction or withdrawal in 67%. In a preliminary analysis we didn’t observe significant differences in terms of clinical and/or radiological response rate, in PFS or OS according to MGMT methylation and 1p/19q codeletion status. There was a better clinical improvement in oligodendroglial subtype after induction phase (75% of patients), while no differences emerged in radiological disease control rate, PFS6, PFS or OS compared to astrocitary histotype. Survival rates of the whole cohort were 34% at 1 year, 21% at 2 years, 14% at 3 years, 7% at 4 years and 5% at 5 years. The pattern of progression was focal enhancing in 73% of tumors, diffuse non-enhancing (gliomatosis-like) in 12%, multicentric in 10% and local plus leptomeningeal in 5%.Twenty-two percent of patients discontinued fotemustine for grade 3/4 myelotoxicity. We did not observe any additional toxicity from the combination.Conclusions:The combination of bevacizumab and fotemustine as salvage treatment for grade III gliomas is safe and somewhat active in this heavily pretreated cohort. Further clinical studies should explore alternative regimens of therapy in the different molecular subgroups.

Long-term follow-up of transplantation of preserved limbal allograft and amniotic membrane for recurrent pterygium.

To conduct a long-term follow-up study evaluating the efficacy and safety of transplantation of preserved limbal allograft and amniotic membrane for recurrent pterygium. This was a retrospective, non-comparative, interventional case series conducted at a private eye hospital. Eighty-four eyes of 80 patients with recurrent pterygium were included in the study. The mean number of previous surgeries for pterygium was 1.36 ± 0.98 (range, 1-8). All subjects received transplantation of preserved limbal allograft and amniotic membrane. The mean follow-up period was 73.0 ± 38.1months (range, 12-154 months). Pterygium recurred in 10 eyes (11.9%). The mean period to recurrence was 16.3 ± 11.3months (range, 5-33 months). Symblepharon was cured in 21 eyes, persisted in 2 eyes, and newly occurred in 3 eyes. Diplopia was cured in eight eyes, persisted in five eyes, and newly occurred in one eye. As for complications, intraocular pressure elevations over 21mmHg were recognized in ten eyes of nine cases, in which the intraocular pressure was controlled by reduction of topical steroid in four eyes and by addition of topical prostaglandin derivatives in six eyes. Twenty-four eyes (28.6%) gained two lines or more of Landolt best spectacle-corrected visual acuity (BSCVA), 56 eyes (66.7%) stayed within one line from preoperation, and four eyes (4.8%) lost two lines or more. There were no major complications and no graft rejection. Transplantation of preserved limbal allograft and amniotic membrane is a safe and effective procedure for recurrent pterygium.

Utility of ultrasonography in guiding modification of disease modifying anti-rheumatic drugs and steroid therapy for inflammatory arthritis in routine clinical practice.

To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA) in routine clinical practice. In this retrospective study, we analyzed DMARD and steroid use in IA patients referred to a rheumatologist-led ultrasound clinic. Power Doppler (PD) vascularity and greyscale (GS) synovial hypertrophy joint findings were categorized as positive/negative for each patient. The erythrocyte sedimentation rate (ESR) was used as a measure of disease activity. We assessed single visit data for 46 adult IA patients: 67.4% (n = 31) rheumatoid arthritis (RA), 15.2% (n = 7) psoriatic arthritis, 10.9% (n = 5) spondyloarthritis, and 6.5% (n = 3) undifferentiated IA. The mean ESR was 28.8 mm/h. Thirty-seven patients with both GS and PD ultrasound results were subsequently analyzed. All patients (n = 10) escalated and/or initiated on DMARD and 9/10 patients escalated or initiated on steroids were PD and GS positive. Six of seven patients with dose reduction and/or cessation of DMARDs and five of seven patients with dose reduction or cessation of steroids were PD negative. Of six patients who were GS positive and PD negative, three had dose reduction and/or cessation of DMARDs, while four had dose reduction of steroids; none of the six patients had DMARD/steroid escalation. By clarifying joint inflammation in an IA cohort with overall low ESR, ultrasonography of physician-selected joints can improve clinical assessment, resulting in treatment modification. Positive PD findings were particularly influential, while the clinical significance of GS positivity alone requires further investigation.

Early pancreatic volume reduction on CT predicts relapse in patients with type 1 autoimmune pancreatitis treated with steroids.

BackgroundType 1 autoimmune pancreatitis (AIP) is clinically characterized by a response to steroid therapy. Despite having a favorable prognosis, AIP has a high relapse rate and factors predicting relapse in AIP patients treated with steroids have not yet been established.MethodsA retrospective chart review was conducted of 32 newly diagnosed type 1 AIP patients who had undergone enhanced computed tomography (CT) pre- and post-steroid therapy.ResultsTen patients experienced relapse. Pancreatic volume was reduced significantly in all patients (pre-treatment volume, 88.5 ± 32.9 cm3 vs. post-treatment volume, 45.4 ± 21.1 cm3; P < 0.001), although the pre-treatment pancreatic volume did not differ between the relapse and non-relapse groups (92.6 ± 10.5 cm3 vs. 86.6 ± 7.1 cm3, P = 0.401). However, the post-treatment pancreatic volume was significantly greater in the relapse group than that in the non-relapse group (56.9 ± 6.3 cm3 vs. 40.2 ± 4.2 cm3, P = 0.008). Similarly, the percent reduction in pancreatic volume was significantly smaller in the relapse group than that in the non-relapse group (36.6 ± 4.7 % vs. 52.1 ± 3.2 %, P = 0.002). Multivariate analysis identified post-treatment pancreatic volume (HR, 1.04, 95 % CI: 1.01–1.08, P = 0.010) and percent reduction in pancreatic volume (HR, 0.87, 95 % CI: 0.79–0.94, P < 0.001) as predictive factors for relapse of type 1 AIP. A post-treatment pancreatic volume of 50 cm3 < (P = 0.009) and a percent reduction in the pancreatic volume of <35 % (P = 0.004) had a significantly high relapse rate. These data suggest that early pancreatic volume changes after steroid therapy may be a useful prognostic value, because type 1 AIP patients with a high post-treatment pancreatic volume or low pancreatic volume reduction showed significant relapse.ConclusionsEarly pancreatic volume reduction on CT after steroid therapy indicates the therapeutic effects of steroids, and a low decrease in the pancreatic volume may be associated with a limited response that predicts future relapse in patients with type 1 AIP. Reduction of steroids in these cases must be observed carefully with consideration of immunomodulator use.

Thalidomide for inflammatory bowel disease: Systematic review.

Thalidomide is an immunomodulatory drug used in the experimental treatment of refractory Crohn disease and ulcerative colitis. We aimed to review the existing evidence on the efficacy and safety of thalidomide in the treatment of inflammatory bowel diseases. CENTRAL, MEDLINE, LILACS, POPLINE, CINHAL, and Web of Science were searched in March 2016. Manual search included conference and reference lists. All types of studies, except single case reports, were included. Outcomes evaluated were: induction of remission; maintenance of remission; steroid reduction; effect on penetrating Crohn disease; endoscopic remission; adverse events. The research strategies retrieved 722 papers. Two randomized controlled trials and 29 uncontrolled studies for a total of 489 patients matched the inclusion criteria. Thalidomide induced a clinical response in 296/427 (69.3%) patients. Clinical remission was achieved in 220/427 (51.5%) cases. Maintenance of remission was reported in 128/160 (80.0%) patients at 6 months and in 96/133 (72.2%) at 12 months. Reduction in steroid dosage was reported in 109/152 (71.7%) patients. Fistulas improved in 49/81 (60.5%) cases and closed in 28/81 (34.6%). Endoscopic improvement was observed in 46/66 (69.7%) and complete mucosal healing in 35/66 (53.0%) patients. Cumulative incidence of total adverse events and of those leading to drug suspension was 75.6 and 19.7/1000 patient-months, respectively. Neurological disturbances accounted for 341/530 (64.3%) adverse events and were the most frequent cause of drug withdrawal. Existing evidence suggests that thalidomide may be a valid treatment option for patients with inflammatory bowel diseases refractory to other first- and second-line treatments.

Reflections on Caring: The White Bike

Granulomatous interstitial nephritis (GIN) is a rare renal disease, and its etiology remains unknown. We report recurrent GIN in renal allograft successfully treated with everolimus (EVR).A 22-year-old man with GIN received a kidney from his mother. On follow-up 8 months later, his serum creatinine level was increased, from 1.3 mg/dL to 1.7 mg/dL, and he had microhematuria and proteinuria. A protocol graft biopsy at 1 year after transplantation showed epithelioid granuloma with multinucleated giant cells. He received steroid pulse therapy for recurrent GIN twice, but he developed allograft dysfunction, hematuria, and proteinuria. EVR was started in combination with maintenance immunosuppressants at 28 months after transplantation. Thereafter, the serum creatinine level decreased, from 2.1 mg/dL to 1.6 mg/dL, and microhematuria and proteinuria were stable despite reduction of steroid dose.Maintenance immunosuppressive therapy combined with EVR may be effective for the recurrence of idiopathic GIN in renal allograft.

Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

This retrospective study describes efficacy of Azacitidine on autoimmune disorders (AID) associated with MDS/CMML in 22 patients. Response of AID to Azacitidine was observed in 19 patients (86%). Reduction or discontinuation of steroids and/or immunosuppressive therapy (IST) was possible in 16 cases (73%). Hematologic response was seen in 55% of the patients. MDS/CMML and AID evolution was concordant in 13 cases (59%): both favorable (n=11), both unfavorable (n=2), but AID improved while MDS/CMML worsened (n=8) and vice versa (n=1). Azacitidine frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings.

Steroid Sparing Response with Mepolizumab: Durability of Steroid Reduction in Severe Asthma

Steroid Sparing Response with Mepolizumab: Durability of Steroid Reduction in Severe Asthma

Pulmonary thromboembolism combined with intracardiac thrombus occurred during the steroid reduction in nephrotic syndrome patient

Pulmonary thromboembolism combined with intracardiac thrombus occurred during the steroid reduction in nephrotic syndrome patient

Extracorporeal Photopheresis (ECP) for Acute Graft-Versus Host Disease (GvHD) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

BackgroundGraft-versus-host disease (GvHD) is a major limitation after allo-HSCT and remains a frequent cause of death. The 5-years survival is 25% and 5% for grade III and IV, respectively. Acute GvHD occurs in up to 45% of HLA-matched and up to 75% in case of unrelated donors. The standard-treatment consists of methylprednisolone (usually 2 mg/kg/day) and a calcineurin-inhibitor. No standardized second-line treatment for acute GvHD exists. Here, we report a pilot single-centre experience with extracorporeal photopheresis (ECP) for acute GvHD: the objective was to investigate the efficacy of ECP for patients with steroid-refractory/-dependent acute GvHD as well as an early intervention in patients with low-grade acute GvHD to avoid/taper steroids. Furthermore, we evaluated the reduction of immunosuppressive therapy.Patients' characteristicsBetween 2013 and 2014, 17 patients with acute GvHD (of whom two patients developed GvHD after donor lymphocyte infusion) were treated. Eight patients had a maximum grade of GvHD I/II (2/6 patients) and nine patients were graded as III/IV (6/3 patients). Organ involvement was as follows: skin only in 10, skin and liver in one, skin and gastrointestinal tract in two and all three organs were involved in four patients.Treatment before ECP consisted of topical steroids in one and 0.5 mg/kg methylprednisolone (due to side-effects of calcineurin-inhibitor) in the other patients with grade I. Six patients received 1 mg/kg and eight patients received 2 mg/kg methylprednisolone. One patient was treated with 2 mg/kg methylprednisolone and weekly methotrexate. Before start of ECP, one patient was steroid-free, six patients were steroid-refractory and nine patients were steroid-dependent. Thus, we treated patients with acute GvHD not only for steroid-refractory disease but also steroid-dependent disease and grade I GvHD to avoid a treatment with steroids.ResultsThe median number of ECP sessions per patient was 12 (range, 5 - 36), seven patients received ECP twice a week. Best response to ECP was complete remission in 71%, partial response in 12% and no response in 17%, after a median number of 6 treatments (range, 2 - 9). Response was better for grade I/II: 87.5% received complete remission compared to 56% with grade III/IV, partial response was observed in 12.5% in patients with grade I/II versus 11% with grade III/IV. No responders comprised 33% with grade III/IV and 0% with grade I/II.Immunosuppressive therapy could be tapered successfully: mean reduction of steroids was 95% (range, 60 - 100) and mean reduction of calcineurin-inhibitor was 83% (range, 40 - 100).Six patients developed a rebound of GvHD during tapering (two patients) or after discontinuation (four patients) of ECP. Eleven patients (78%) developed chronic GvHD (two patients with severe grade), whereas it appeared in four patients during tapering of ECP and in seven patients after discontinuation of ECP after a median time of 116 days (range, 30 - 287).We could observe seven bacterial, 14 viral and one fungal infection in 14 patients, which are expected rates after allo-HSCT in patients with acute GvHD. After a median follow up of one year, two patients relapsed from their underlying disease and five patients died (one due to relapse and four due to infections).ConclusionIn this single-centre pilot experience, we could show that ECP is an efficient and safe treatment in patients with steroid-refractory or steroid-dependent acute GvHD as well as an upfront-treatment in patients with low-grade GvHD. We were able to taper immunosuppressive therapy with a mean reduction of steroids of 95% and mean reduction of calcineurin-inhibitor of 83%.Best responses were seen in patients with I/II grade GvHD which concludes that ECP should be started as early as possible.Further studies are warranted to investigate a schedule to reduce the risk of rebound of acute GvHD (42% in our cohort) and development of chronic GvHD (78%). DisclosuresMohty:Janssen: Honoraria; Celgene: Honoraria.