Reduction In Steroid Use Research Articles

Acute psychosis following corticosteroid administration for COVID-19 and Respiratory Syncytial Virus infection: A case study

IntroductionSteroids are a necessary treatment for hypoxic respiratory failure; however there are many side effects that should be taken into account. A 44- year-old-woman with asthma and no past psychiatric history was admitted due to COVID-19 pneumonia and Respiratory syncytial virus (RSV) infection, presenting hypoxic respiratory failure. After two days of intravenous methylprednisolone administration, the patient presented acute psychosis and agitation.It has been previously described that steroid use can cause effects such as mania, anxiety, agitation, delirium and psychosis amongst other. However they are a necessary treatment in respiratory illnesses and are sometimes unavoidable.Objectives The aim was to examine the appropriate medical response to steroid induced psychosis in patients with acute hypoxic failure.MethodsA bibliographical review was done in PubMed database searching recent cases of steroid induced psychosis using the words (“Steroid”, “Psychosis” and “COVID-19”).Results According to literature, it has been shown that partial or complete reduction of steroid use and/or use of psychotropic has been successfully used to treat steroid induced psychosis. Following the research it was decided to reduce intravenous methylprednisolone dose from 20mg/ 8h to 20mg/12h and start oral haloperidol 5mg/8h the first 24h and reducing the dose progressively as the patient recovered. After the first 24 hours the patient presented adequate response to steroids as well as partial response to antipsychotic treatment; presenting no further agitation, absence of hallucinations and partial persistence of the persecutory delusion. A couple of days later there was complete remission of the psychotic symptoms and the patient was on the way to recovery from COVID-19 and RSV.ConclusionsThere is evidence that suggests that medications such as steroids used to treat COVID-19 and other respiratory illnesses can lead to psychotic episodes. It is very important to pay attention to possible side effects when treating with steroids and evaluate the patient history as well as suggest having a follow up visit after the hospital discharge.Disclosure of InterestNone Declared

DIPG-02. Role of a Bevacizumab-based regime in the treatment of children with diffuse intrinsic pontine glioma (DIPG): a systematic review

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is an aggressive paediatric brainstem tumour. There are no effective treatments and median survival is 11.2 months, therefore maintaining quality of life (QOL) is a priority for many families. Bevacizumab, an anti-VEGF IgG antibody, has the potential to improve QOL and survival in DIPG, but has never been evaluated systematically. AIM: To collate the evidence and assess the role of this drug, in the treatment of DIPG. METHODS: MEDLINE, EMBASE, Scopus and Web of Science were searched for relevant studies using terms developed from PICO criteria, including alternatives for Bevacizumab and DIPG. One reviewer screened titles and abstracts, then two reviewers screened full texts. Data were extracted into tables and study quality assessed using MINORS and JBI tools. RESULTS: Searching revealed 1,001 papers; after deduplication 851 remained. After screening of titles and abstracts, 28 full texts were screened, resulting in the inclusion of 11 studies. All studies evaluated more than one outcome. Four studies reported a median overall survival longer than historical data, however, two determined no significant impact. Five studies reported a radiological response in a proportion of participants and two reported no response. Three studies evaluating clinical response, reported improvement in a proportion of patients. Three studies evaluating QOL reported stability or improvement. Four studies evaluating steroid use reported reductions in the proportion of patients receiving steroids. In the treatment of radiation necrosis, Bevacizumab led to clinical improvement in 6/12 patients in 2 studies and permitted a reduction in steroid use in the majority of patients. CONCLUSION: Insufficient evidence means the role of Bevacizumab in the treatment of DIPG is unclear. However, Bevacizumab may be beneficial to some patients. The review highlights the need for further research in this area, particularly randomised controlled trials. More effective therapies are desperately needed.

Does a Bevacizumab-based regime have a role in the treatment of children with diffuse intrinsic pontine glioma? A systematic review.

BackgroundThere are no effective treatments for diffuse intrinsic pontine glioma (DIPG); median survival is 11.2 months. Bevacizumab has the potential to improve quality of life (QOL) and survival in DIPG but has never been evaluated systematically. The aim of this review was to assess Bevacizumab’s role in the treatment of DIPG.MethodsMEDLINE, EMBASE, Scopus, and Web of Science were searched for relevant studies using terms developed from alternatives for Bevacizumab and DIPG. One reviewer screened titles and abstracts, then two reviewers screened full texts. Data were extracted into tables and quality assessed using methodological index for non-randomized studies and JBI tools.ResultsSearching revealed 1001 papers; after deduplication 851 remained. After screening of titles and abstracts, then 28 full texts, 11 studies were included. Four studies reported a median overall survival longer than historical data, however, two found no significant impact of Bevacizumab. Five studies reported a radiological response in a proportion of participants and two reported no response. Three studies, evaluating clinical response, reported improvement in a proportion of patients. Three studies, evaluating QOL, reported stability or improvement. Four studies, evaluating steroid use, reported reductions in the proportion of patients receiving steroids. In radiation necrosis treatment, Bevacizumab led to clinical improvement in 6/12 patients in 2 studies and permitted a reduction in steroid use in most patients.ConclusionsInsufficient evidence means the role of Bevacizumab in the treatment of DIPG is unclear. However, Bevacizumab may be beneficial to some patients. The review highlights the need for further research in this area.

Infliximab De-escalation in Patients With Crohn's Disease in Clinical Remission Is Safe and Well-tolerated.

Infliximab—a chimeric monoclonal antibody that targets antitumor necrosis factor (TNF) alpha—is an effective biological agent to treat inflammatory bowel disease (IBD).1 Infliximab has demonstrated long-term therapeutic benefits in moderate to severe Crohn’s disease (CD) with associated improvements in quality of life, endoscopic healing, and reduction in steroid use.2 After induction, infliximab is administered as maintenance therapy to maintain clinical remission. Drug concentrations may vary based on disease severity, inflammation, and other drug clearance mechanisms,3 and therefore therapeutic drug monitoring (TDM) is often needed to optimize dosing while also monitoring for antidrug antibodies.4 Infliximab dose escalation in patients with CD is recommended in the setting of waning clinical response and low drug trough levels. The need to dose escalate, however, does not necessarily represent a linear deterioration of disease but rather a transient process that requires a subsequent re-evaluation of the dose and frequency of drug administration....

P654 Prevalence of Inflammatory Bowel Disease in young Greek Army male recruits from 2006 to 2018: a thirteen-year retrospective study from a tertiary center

Abstract Background Prevalence and incidence of Inflammatory Bowel Diseases (IBD), vary among different countries. Data regarding prevalence of IBD in Greece are limited or outdated. Methods We studied retrospectively, using the official Hospital electronic-form database, medical records of IBD patients from a population of 551,808 Greek Army candidates for recruitment in a thirteen-year period from 2006 to 2018. Study population consisted of males aged 18 to 37 from Northwest, Central Greece (including Athens) and South Aegean Islands. Age, disease distribution, surgery and pharmaceutical treatment at the time of patients’ admission were recorded. Results Prevalence of IBD among male recruits during the studied period was 0.15% (n=839 patients), (95% confidence interval = 0.14% to 0.16%). Out of them, 448 (53.4%) had Crohn’s Disease (CD) and 391 (46.6%) Ulcerative Colitis (UC). Figures 1 & 2 illustrate the percentages of pharmaceutical treatment for CD and UC respectively, while figures 3 & 4 their distribution and fluctuation during the studied period for CD and UC respectively . Concerning CD cases, monotherapy with biologics was the most commonly used pharmaceutical choice (32.1%) with Infliximab being the predominant one (60% of them), though azathioprine had been used more often than any other isolated drug agent (27%). Interestingly, 21% of CD patients received 5-ASA as monotherapy, mainly in cases of mild CD colitis or terminal ileitis. Among UC patients, mesalamine was the most often prescribed treatment (64.2%), while biological drugs and combination therapy were not so widely administered as in CD (ratio 1:2). During the recorded period for CD patients we noticed that: i) there was a reducing trend in azathioprine prescription, ii) adalimumab presented to be an increasing predilection iii) infliximab’s use was maintained at the same level all these years. Among UC cases, mesalamine was constantly the first choice, while adalimumab was not so widely administered as in CD. A distinct reduction in steroid use was noted from 2006 to 2018, coming alongside with biologics establishment. Additionally, 8% of CD and 2.8% of UC patients had undergone a surgery due to disease complications. This low proportion could be explained by the relatively young age of the study population. Conclusion Prevalence of IBD in Greek recruits was 0.15% with a slight CD predominance. This is the first Greek epidemiological study that recorded also the provided treatment at the time of patient’s admission giving useful information upon IBD epidemiological profile in a wide region of our country and contributing to quantification of public health burden of those diseases in Greece.

Prevalence of inflammatory bowel disease in young Greek Army male recruits from 2006 to 2018: a 13-year retrospective study from a tertiary center.

The prevalence and incidence of inflammatory bowel diseases (IBDs) vary among countries. Data regarding prevalence of IBD in Greece are limited or outdated. We reviewed the medical records of IBD patients from a population of 551,808 Greek Army recruits in a 13-year period (2006-2018). Study population consisted of males 18-37 of age from Northwest, Central Greece (including Attica), Peloponnese, and Aegean Sea Islands. Age, disease distribution, pharmaceutical treatment and IBD-related surgery at the time of patients' admission were recorded. The prevalence of IBD among male recruits during the studied period was 0.15% (839/551 808, 95% confidence interval 0.14-0.16%). Of these, 448 (53.4%) had Crohn's disease (CD) and 391 (46.6%) ulcerative colitis (UC). Although 32.1% of CD patients had been treated with biologics, most often infliximab (60% of them), azathioprine was the most common as monotherapy (27% of patients). Among UC patients, mesalamine was the most often prescribed treatment (64.2%), whereas treatment with biologics as monotherapy or in combination with azathioprine was used in a ratio 1:2 compared to CD patients. A gradual reduction in steroid use was noted from 2006 to 2018, coinciding with the advent and increasing use of biologics. IBD-related surgery had been performed in 8% and 2.8% of CD and UC patients, respectively. The prevalence of IBD in Greek male recruits was 0.15% with a slight CD predominance. Remarkable changes in therapeutic trends were noted with an increasing use of biologics and reduced prescription of steroids, especially for CD.

Ustekinumab in Crohn's disease: Real-world outcomes from the Sicilian network for inflammatory bowel diseases.

Background and AimUstekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real‐life data are scarce, so the aim of this study was to assess the effectiveness and safety of ustekinumab in an Italian cohort of CD patients.MethodsData of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end‐points were steroid‐free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C‐reactive protein. Secondary end‐points were treatment response, treatment persistence at 12 months, and safety.ResultsA total of 131 patients (males 56%; mean age 46 years ±15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid‐free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow‐up, there was a significant reduction of steroid use (P = 0.012) and of the Harvey‐Bradshaw Index (P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age.ConclusionsData from our real‐life cohort of treatment‐refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab.

PGI16 A Structured Literature Review of Modelling Approaches for Steroid Use and Treatment Stopping Rules in Ulcerative Colitis for Economic Evaluation

To review the evidence on systemic corticosteroid use and treatment stopping rules from literature and health technology assessment (HTA) critiques, and to assess the impact on health economic modelling in ulcerative colitis (UC). Electronic databases and citation searching were used to identify studies and critiques written in English, reporting steroid use and treatment stopping rules, without time constraints. Data extraction was performed by one reviewer and checked by a second reviewer. Methodological quality of included studies was assessed by both reviewers. This study identified and screened 66 studies reporting information on steroid use and treatment stopping rules, with 61 studies meeting the criteria for inclusion. Forty studies recognized patient quality of life implications associated with long-term steroid usage, however only 3 modelled the impact of steroid reduction or steroid-free remission on cost-effectiveness. One study modelled linear reduction in steroid use over 54-weeks in the intervention arm, with patients assumed as steroid free in future cycles if classified as steroid free at week 54. Stopping rules were more common in and primarily based on patient’s non-response to treatment during induction phases, loss of response during maintenance phases, and discontinuation due to adverse events, accounting for 53 studies. No studies modelled dynamic treatment posology despite NICE requesting functionality related to remission-based temporary discontinuations within economic models to better reflect real-world clinical practice. In addition to applying stopping rules for treatment effectiveness and associated adverse events in UC, it could be useful to include remission-based discontinuation within the models. There exists a need for modelling the steroid-sparing effects of therapies. HTAs may encourage such UC models to better reflect clinical practice.

Antagonists of chemokine receptor CCR9 synergize with anti-TNFα immunotherapy to reduce inflammation in the MDR1a−/− mouse model of colitis

Abstract The development of anti-TNFα immunotherapies has led to great advances in quality of life for Crohn’s and colitis patients, and has allowed a reduction in steroid use for these diseases. However, a significant proportion of IBD patients is resistant to anti-TNFα agents, or becomes resistant over time. Preclinical research and clinical trials suggest that CCR9 antagonism can effectively reduce colon inflammation. CCR9 is expressed on a subset of T cells dedicated to intestinal trafficking. Antagonism of this receptor inhibits the accumulation of T cells within inflamed intestinal epithelium and lamina propria. Since anti-TNFα and CCR9 antagonists act through entirely different mechanisms, we asked whether these two approaches might synergize and expand the effectiveness and scope of each therapy. We used a piroxicam-accelerated version of the MDR1a−/− spontaneous colitis model in mice. We have found that combined dosing of piroxicam-fed MDR1a−/− mice with a CCR9 antagonist and an anti-TNFα MAb significantly reverses loss of body weight, diarrhea score and colon inflammation. The combined dosing was more effective than anti-TNFα or CCR9 antagonist alone, as measured by colon length/weight ratio, neutrophil accumulation in the colonic epithelium and reversal of the loss in body weight characteristic of this model. These data suggest that combining a CCR9 antagonist with existing anti-TNFα treatment regimens may extend the benefits of anti-TNFα immunotherapy to a larger class of patients suffering from IBD, and may prolong the effectiveness of anti-TNFα immunotherapy for those patients already undergoing such treatments.

O28 Has modern UK management of RA led to a reduction in use of steroids and NSAIDs? 20-year data from the clinical practice research datalink

Abstract Background Over 20 years, rheumatoid arthritis (RA) management has evolved to immediate initiation and more effective escalation of disease-modifying anti-rheumatic drugs (DMARDs) to suppress inflammation. We aimed to establish whether this has facilitated reduced long-term use of potentially toxic glucocorticosteroids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Methods We investigated changes in DMARD, oral GC and NSAID prescribing over 1998-2017 in a UK primary care electronic health records database. We defined RA by coded diagnosis, sensitivity analyses requiring (a) two diagnoses ≥6 months apart; (b) ≥1 DMARD prescriptions. We calculated annual RA incidence and prevalence, annual prescribing and prescribing in the first to fifteenth year from diagnosis. Long-term prescribing was defined as ≥ 3 months (≥6 in a sensitivity analyses) and compared with a non-RA cohort (5:1 matched on age, sex and GP practice). Results We included 71,411 RA patients (44,426 with 2 diagnoses, 45,438 with DMARD). Incidence declined from 5.01 (±0.36) per 10,000 person-years in 1998 to 4.77 (±0.23) in 2011, before increasing following changes in Quality Outcomes Framework indicators. Prevalence rose from 0.70% (±0.013) in 1998 to 0.91% (±0.014) in 2017 and was highest among patients aged ≥70 (2.21%, ±0.05). Long-term DMARD prescribing rose from 30.97% in 1998 to 49.28% in 2017. Long-term NSAID prescribing fell (45.94% to 25.08%) particularly amongst incident RA patients, with only modest change in GCs (20.98% to 15.53%) (Table 1). By comparison, long-term GC prescribing in the matched non-RA population rose (0.90% to 2.01%) and NSAID prescribing changed little (6.37% to 8.41%). The proportion with long-term prescribing declined slightly from the first to the third year following diagnosis for GCs (22.18% to 17.87%) and NSAIDs (41.19% to 34.30%). Sensitivity analyses showed similar results. Conclusion Long-term GC prescribing among newly diagnosed RA patients has not appreciably reduced despite modern treatment paradigms and the expected observed increase in DMARD prescribing. Long-term NSAID prescribing did decrease in primary care for RA (especially from mid-2000 and among newly diagnosed patients), but interestingly, not for non-RA patients. Given the scope for further reduction in GC and NSAID prescribing, the reasons for persistent prescribing, including prescribing behaviours, require further investigation. Disclosures S.S.R. Crossfield: Grants/research support; Medical Research Council (MRC) Leeds Medical Bioinformatics Centre [MR/L01629X]. M.H. Buch: None. P. Baxter: None. S.R. Kingsbury: Grants/research support; National Institute for Health Research (NIHR) Leeds Biomedical Research Centre and the Versus Arthritis Experimental Osteoarthritis Treatment Centre [20083]. M. Pujades-Rodriguez: None. P.G. Conaghan: Grants/research support; National Institute for Health Research (NIHR) Leeds Biomedical Research Centre and the Versus Arthritis Experimental Osteoarthritis Treatment Centre [20083].

P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results

Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP). Results One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p < 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1). Conclusion Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.

P037 Antagonism of chemokine receptor CCR9 synergises with anti-TNFα immunotherapy to reduce inflammation in the MDR1a−/− mouse model of colitis

Abstract Background The development of anti-TNFα immunotherapies has led to great advances in quality of life for Crohn’s and colitis patients and has allowed a reduction in steroid use for these diseases. However, a significant proportion of IBD patients is resistant to anti-TNFα agents, or becomes resistant to such treatments over time. Preclinical research and clinical trials have suggested that CCR9 antagonism can effectively reduce colon inflammation. CCR9 is expressed on a subset of T cells dedicated to monitoring the immune status of the intestine. When activated by its only known chemokine ligand, CCL25/TECK, CCR9 triggers the adhesion of gut-specific T cells to vascular endothelium and the subsequent ingress of these cells to intestinal tissues. Antagonism of this receptor inhibits the accumulation of T cells within inflamed intestinal epithelium and lamina propria. Since anti-TNFα and CCR9 antagonists act through entirely different mechanisms, we asked whether these two approaches might synergise and expand the effectiveness and scope of each therapy. Methods We used a piroxicam-accelerated version of the MDR1a−/− spontaneous colitis model in mice. In this model, 7week MDR1a−/− mice (or WT FVB controls) receive piroxicam in powdered chow for 10 days. Mice are monitored both during and after the piroxicam feeding period, for a total of 21 days. Treatment groups (eight mice each) include an antibody (a saturating dose of either anti-TNFα or its isotype-matched control) and a CCR9 antagonist (or its vehicle alone as a control). Body weight and diarrhoea score were recorded throughout the entire 21 days period, after which colons were obtained from sacrificed animals for weighing, length measurement and imaging. Results We have found that combined dosing of piroxicam-fed MDR1a−/− mice with a CCR9 antagonist and an anti-TNFα MAb significantly reverses loss of body weight, diarrhoea score and colon inflammation. The combined dosing was more effective than anti-TNFα or CCR9 antagonist alone, as measured by colon length/weight ratio, neutrophil accumulation in the colonic epithelium and reversal of the loss in body weight characteristic of this model. Conclusion These data suggest that combining a CCR9 antagonist with existing anti-TNFα treatment regimens may extend the benefits of anti-TNFα immunotherapy to a larger class of patients suffering from IBD and may prolong the effectiveness of anti-TNFα immunotherapy for those patients already undergoing such treatments.

Clinical Course and Dietary Patterns Among Patients Incorporating the Autoimmune Protocol for Management of Inflammatory Bowel Disease (P12-010-19)

ObjectivesThe aim was to examine the clinical course and dietary patterns among patients incorporating autoimmune protocol (AIP) for management of inflammatory bowel disease (IBD). MethodsAn anonymous online survey was sent through electronic newsletters and support groups utilizing AIP. The survey assessed demographics, IBD disease activity, and medication use. Participants were asked about AIP utilization and food group reintroductions. Abdominal pain (AP), stool frequency (SF), and rectal bleeding (RB) were compared at baseline (BL, prior to starting AIP), week 6 (after starting AIP), and present, for both Crohn’s disease (CD) and ulcerative colitis (UC). ResultsThere were 78 respondents. Mean age was 39.4 years, with mean IBD duration 13.2 years. 78% had prior steroid exposure. 35% currently on immunosuppressive agents. 73% perceived achieving clinical remission due to AIP. This was more common among patients not on immunosuppression (76% vs. 24% on immunosuppression, P < 0.001). After starting AIP, 32% reported discontinuing steroids. AIP was initiated according to protocol by 73%, while 27% modified it. Food group reintroductions were started within 0–4 weeks of starting AIP among 8%, while 23% reintroduced within 5–8 weeks, 24% within 2–6 months, 23% within 6–12 months, and 13% after 12 months. Success of food group reintroductions varied (Table 1).Among patients with CD, improvement by ≥1 levels of symptoms by week 6 was reported by 77% for AP, 57% for SF, and 57% for RB. Compared to BL, reported symptoms improved by ≥1 levels in 70% for AP, 53% for SF, and 57% for RB. In contrast, disease worsening by ≥1 levels at week 6 was reported by 7% for AP and none for SF and RB.Among patients with UC, improvement by ≥1 levels by week 6 was reported by 72% for AP, 79% for SF, and 65% for RB. Compared to BL, reported symptoms improved by ≥1 levels in 65% for AP, 67% for SF, and 58% for RB. In contrast, disease worsening by ≥1 levels at week 6 was reported by 2% for AP, 2% for SF, and 5% for RB. ConclusionsPatients utilizing AIP for management of IBD report clinical benefit of AIP, reduction of steroid use, and successful food group reintroduction. Dietary interventions could be another form of treatment in patients with IBD to improve symptoms and maintain remission. Funding SourcesNot applicable. Supporting Tables, Images and/or Graphs▪

Concomitant immunosuppressant use with pegloticase in patients with tophaceous gout - A case series

Introduction: Treatment of tophaceous gout with pegloticase is often complicated by the production of anti-pegloticase antibodies. These antibodies result in increased risk of infusion reactions, loss of drug efficacy, and high discontinuation rate. Steroids are used in premedication to reduce potential infusion reactions; however prolonged usage of steroids is associated with significant adverse effects. Objective: To describe the use of immunosuppressants to reduce the incidence of infusion reactions with pegloticase treatment and the potential reduction of steroid use in premedication. Methods: We report seven cases of immunosuppressant use, initiated on the day of the first pegloticase infusion, as an adjunct to treatment with pegloticase for tophaceous gout. Results: Patient 1 was treated for tophaceous gout with oral methotrexate initiated at his first infusion. Low serum urate levels were achieved but urate increased on two occasions after two separate lapses in methotrexate compliance. In each instance, initiation of a higher dose of methotrexate restored pegloticase response. The patient tolerated all treatments without infusion reaction. Patients 2-6 were treated for tophaceous gout with oral methotrexate initiated at their first infusions. For Patient 2, methotrexate was switched to azathioprine at her fifth infusion due to fatigue. All five patients achieved low serum uric acid (sUA) levels, completed their treatments, and did not experience infusion reactions. Patient 7 was treated for tophaceous gout with oral cyclosporine initiated at his first infusion. Methotrexate was not used due to elevated liver function enzymes at baseline. He achieved a low sUA level and was able to complete his treatment without experiencing an infusion reaction. All of the patients were able to decrease their steroid use in pre-medication. Six of the seven were able to discontinue steroid use in pre-medication without developing infusion reactions. Conclusion: Concomitant use of immunosuppressive therapy with pegloticase may play a role in preventing infusion reactions, allow reduction of steroids in pre-medication, and result in improved outcomes. We have demonstrated that immunosuppressive therapy may be initiated on the day of the first infusion. Additionally, therapy does not seem to be confined to a single immunosuppressant; thus, immunosuppressive therapy may be tailored to a patient’s needs. The use of concomitant immunosuppressants with pegloticase treatment warrants further study.

A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study...

Bevacizumab for Patients with Recurrent Gliomas Presenting with a Gliomatosis Cerebri Growth Pattern.

Bevacizumab has been shown to improve progression-free survival and neurologic function, but failed to improve overall survival in newly diagnosed glioblastoma and at first recurrence. Nonetheless, bevacizumab is widely used in patients with recurrent glioma. However, its use in patients with gliomas showing a gliomatosis cerebri growth pattern is contentious. Due to the marked diffuse and infiltrative growth with less angiogenic tumor growth, it may appear questionable whether bevacizumab can have a therapeutic effect in those patients. However, the development of nodular, necrotic, and/or contrast-enhancing lesions in patients with a gliomatosis cerebri growth pattern is not uncommon and may indicate focal neo-angiogenesis. Therefore, control of growth of these lesions as well as control of edema and reduction of steroid use may be regarded as rationales for the use of bevacizumab in these patients. In this retrospective patient series, we report on 17 patients with primary brain tumors displaying a gliomatosis cerebri growth pattern (including seven glioblastomas, two anaplastic astrocytomas, one anaplastic oligodendroglioma, and seven diffuse astrocytomas). Patients have been treated with bevacizumab alone or in combination with lomustine or irinotecan. Seventeen matched patients treated with bevacizumab for gliomas with a classical growth pattern served as a control cohort. Response rate, progression-free survival, and overall survival were similar in both groups. Based on these results, anti-angiogenic therapy with bevacizumab should also be considered in patients suffering from gliomas with a mainly infiltrative phenotype.

The use of rituximab in newly diagnosed patients with systemic lupus erythematosus: long-term steroid saving capacity and clinical effectiveness

BackgroundPrevious reports indicate that treating patients with lupus (SLE) at or close to the time of diagnosis successfully without using any, or minimal, corticosteroids by using B-cell depletion (BCD) is...

Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA

ObjectiveTo examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting.MethodsThis observational cohort study...

Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma: A Systematic Review

Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule, there has been particular interest in the drug's safety. To establish the efficacy and safety of subcutaneous omalizumab as add-on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed. Primary outcomes were reduction of steroid use and asthma exacerbations. Secondary outcome measures included lung function, rescue medication use, asthma symptoms, health-related quality of life, and adverse effects. Eight trials (3,429 participants) fulfilled the selection criteria. At the end of the steroid-reduction phase, patients taking omalizumab were more likely to be able to withdraw from corticosteroids completely compared with those taking placebo (relative risk [RR] = 1.80; 95% CI, 1.42-2.28; P = .00001). Omalizumab patients showed a decreased risk of asthma exacerbations at the end of the stable (RR = 0.57; 95% CI, 0.48-0.66; P = .0001) and adjustable-steroid phases (RR = 0.55; 95% CI, 0.47-0.64; P = .0001); post-hoc analysis suggests this effect was independent of duration of treatment, age, severity of asthma, and risk of bias. The frequency of serious adverse effects was similar in the omalizumab (3.8%) and placebo (5.3%) groups. However, injection site reactions were more frequent in the omalizumab patients (19.9% vs 13.2%). There were no indications of increased risk of hypersensitivity reactions, cardiovascular effects, or malignant neoplasms. Data indicate that the efficacy of add-on omalizumab in patients with moderate-to-severe allergic asthma is accompanied by an acceptable safety profile.

Management of Graves’ orbitopathy in Latin America: an international questionnaire study compared with Europe

Management of Graves' orbitopathy (GO) and dysthyroid optic neuropathy (DON) continues to be challenging. Other surveys have been successful in elucidating trends in GO management. Knowledge of current practice by members of the Latin American Thyroid Society (LATS) who manage patients with GO was targeted by distribution of a questionnaire. We compared our results with a previously reported European Thyroid Association (ETA) survey. To determine how endocrinologists in Latin America access and treat patients with GO and compare the results with the same European survey. One hundred and two responders representing endocrinologists from 10 countries participated in the survey. Most (57%) participate in a multidisciplinary setting for GO management. Access to a surgeon for orbital decompression was available only 'within months' according to 48.3% of responders. Despite suspected DON, 32.4% were reluctant to recommend urgent referral to an eyecare physician. Steroids were preferred as the first-option therapy by 88.2% of responders (by intravenous route by 57.8% of these). The presence of diabetes reduced the use of steroids to 64.7% (P < 0.001) and increased the use of other immunosuppressive agents (from 1% to 9.8%, P < 0.01). Development of cushingoid features resulted in a reduction in steroid use to 40.2% (P < 0.001), with increased preference for irradiation (from 23.5% to 52.9%, P < 0.001) and nonsteroidal immunosuppressive drugs (from 1% to 10.8%, P < 0.01), along with a nonsignificant trend to higher indication of orbital surgery (from 24.5% to 34.3%). Some potential deficiencies in the diagnosis and management of DON and hyperthyroidism were observed in our survey, highlighting the need for improvement in specialist education and the quality of care offered to patients with GO in Latin America.