Concomitant Corticosteroid Therapy Research Articles

Vitamin D Metabolism Parameters and Cytokine Profile in COVID-19 Patients with Bolus Cholecalciferol Supplementation.

This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context.

P576 Fecal calprotectin could predict clinical and endoscopic response to ustekinumab therapy

Abstract Background Ustekinumab (UST) is one of the most used biologic drugs for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, not all patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response in this setting, with particular regard to mucosal healing. The aim of this multicenter study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. Methods We enrolled consecutive patients with CD or UC treated with UST for at least 48 weeks at four referral centers in the last 5 years. Therapeutic response was evaluated in terms of clinical remission (defined as a Partial Mayo Score <2 for patients with UC and as Harvey Bradshaw Index <5 for patients with CD, without concomitant corticosteroid therapy) and mucosal healing (defined as a Mayo Endoscopic Score <2 for UC and as the disappearance of ulcers for CD). We collected clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and at week 24. Results Among 196 patients enrolled (73 [37.2%] women), 167 were affected by CD, whereas 29 by UC. Globally, 128 (65.3%) patients achieved clinical remission and 83 (42.3%) endoscopic remission at 48 weeks of treatment. There were no group differences in age, sex, BMI, baseline clinical and endoscopic indexes, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [interquartile range] 391 [103, 1050] versus 825 [317, 1800] µg/mL,p=0.002). At week 24, lower calprotectin levels were observed in both the groups who achieved clinical (160 [50, 426] versus 439 [146, 1000] µg/mL,p<0.0001) and endoscopic remission (114 [43, 265] versus 392 [139, 912] µg/mL,p<0.0001) compared with non-responders. The effects of week-24 calprotectin levels on clinical remission (β= -0.003,p<0.0001) and endoscopic remission (β= -0.004,p<0.0001) remained significant in multivariable models adjusted for age, sex, and BMI. A cut-point of 268 µg/mL was identified as the optimal threshold of week-24 calprotectin for predicting clinical remission (sensitivity 65%, specificity 67%, ROC AUC 0.689), while a cut-point of 309 µg/mL was identified to predict endoscopic remission (sensitivity 79%, specificity 59%, ROC AUC 0.712). Conclusion Our data suggest that FC assessment after 24 weeks of treatment with UST could represent a promising early marker of response, even in terms of mucosal healing, in both CD and UC.

Short-term inhalation of sargramostim with concomitant high-dose steroids does not hasten recovery in moderate COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial

Background Granulocyte-macrophage colony stimulating factor (GM-CSF) inhalation may alleviate pulmonary inflammation caused by viral pneumonia. To investigate this, we evaluated its efficacy on COVID-19 pneumonia. Methods This double-blind, randomised, placebo-controlled study (ClinicalTrials.gov: NCT04642950) evaluated patients in the first half of 2021 at seven Japanese hospitals. Hospitalised patients with COVID-19 pneumonia with moderate hypoxaemia inhaled sargramostim or placebo for 5 days. The primary endpoint was days to achieve a ≥ 2-category improvement from baseline on a modified 7-category ordinal scale. Secondary endpoints included degree of oxygenation, defined by amount of oxygen supply, and serum CCL17 level. Results Seventy-five patients were randomly assigned in a 2:1 ratio to receive sargramostim or placebo, of which 47 and 23 were analysed, respectively. No difference was observed between groups regarding the primary endpoint (8.0 and 7.0 days for sargramostim and placebo, respectively) or in the secondary endpoints, except for CCL17. A post hoc sub-analysis indicated that endpoint assessments were influenced by concomitant corticosteroid therapy. When the cumulative corticosteroid dose was ≤500 mg during Days 1–5, recovery and oxygenation were faster in the sargramostim group than for placebo. Bolus dose corticosteroids were associated with temporarily impaired oxygenation and delayed clinical recovery. The increase in serum CCL17, a candidate prognostic factor, reflected improvement with sargramostim inhalation. The number of adverse events was similar between groups. Two serious adverse events were observed in the sargramostim group without causal relation. Conclusions Inhaled sargramostim was likely to be effective for COVID-19 pneumonia unless the concomitant corticosteroid dose was high.

Infectious risk when prescribing rituximab in patients with hypogammaglobulinemia acquired in the setting of autoimmune diseases

We conducted a single-centre retrospective cohort study in a French University Hospital between 2010 and 2018 to describe the risk of severe infectious event (SIE) within 2 years after the date of first rituximab infusion (T0) prescribed after the evidence of acquired hypogammaglobulinemia (gamma globulins [GG] ≤ 6 g/L) in the setting of autoimmune diseases (AID) other than rheumatoid arthritis. SIE occurred in 26 out of 121 included patients. Two years cumulative incidence rates were 12.7 % (95 % CI 5.1–23.9) in the multiple sclerosis/neuromyelitis optica spectrum disorder group (n = 48), 27.6 % (95 % CI 15.7–40.9) in the ANCA-associated vasculitis group (n = 48) and 30.6 % (95 % CI 13.1–50.3) in the ‘other AID’ group (n = 25). Median GG level at T0 was 5.3 g/l (IQR 4.1–5.6) in the 'SIE' group and 5.6 g/l (IQR 4.7–5.8) in the 'no SIE' group (p = 0.04).In regression analysis, risk of SIE increased with Charlson comorbidity index ≥ 3 (OR 2.77; 95 % CI 1.01–7.57), lung disease (OR 3.20; 95 % CI 1.27–7.99), GG < 4 g/L (OR 3.39; 95 % CI 1.02–11.19), concomitant corticosteroid therapy (OR 4.13; 95 % CI 1.63–10.44), previous cyclophosphamide exposure (OR 2.69; 95 % CI 1.10–6.61), a lymphocyte count < 1000 cells/µL (OR 2.86; 95 % CI 1.12–7.21) and absence of pneumococcal vaccination (OR 3.50; 95 % CI 1.41–8.70).These results may help to inform clinical decision when considering a treatment by rituximab in immunosuppressed AID patients with hypogammaglobulinemia.

Choroidal Granuloma as an Initial Manifestation of Systemic Tuberculosis: A Case Report

Purpose: To describe the presentation and management of presumed ocular tuberculosis, successfully treated with anti-tubercular therapy alone. Case Report: Presumed tuberculous choroidal granuloma associated with serous retinal detachment healed after initiation of antituberculosis therapy without concomitant corticosteroid therapy. Conclusion: Although corticosteroids are often used as add-on treatment for ocular tuberculosis, selected patients can be treated with anti-tuberculosis therapy alone with close follow-up.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic.

Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relation to concomitant corticosteroid therapy and safety were unproven despite widespread use in numerous studies, mostly open label at the start of the pandemic. Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until 20 July 2020 (PROSPERO CRD42020195690). Subgroup analyses and meta-regressions were performed. The impact of tocilizumab and concomitant corticosteroid therapy or tocilizumab alone versus standard of care (SOC) on the death rate, need for mechanical ventilation, ICU admission and bacterial infections were assessed. Results. Thirty-nine studies with 15,531 patients (3657 cases versus 11,874 controls) were identified. Unadjusted estimates (n = 28) failed to demonstrate a protective effect of tocilizumab on survival (OR 0.74 ([95%CI 0.55–1.01], p = 0.057), mechanical ventilation prevention (OR 2.21 [95%CI 0.53–9.23], p = 0.277) or prevention of ICU admission (OR 3.79 [95%CI 0.38–37.34], p = 0.254). Considering studies with adjusted, estimated, tocilizumab use was associated with mortality rate reduction (HR 0.50 ([95%CI 0.38–0.64], p < 0.001) and prevention of ICU admission (OR 0.16 ([95%CI 0.06–0.43], p < 0.001). Tocilizumab with concomitant steroid use versus SOC was protective with an OR of 0.49 ([95%CI 0.36–0.65], p < 0.05) as was tocilizumab alone versus SOC with an OR of 0.59 ([95%CI 0.34–1.00], p < 0.001). Risk of infection increased (2.36 [95%CI 1.001–5.54], p = 0.050; based on unadjusted estimates). Conclusion: Despite the heterogeneity of included studies and large number of preprint articles, our findings from the first eight of the pandemic in over 15,000 COVID-19 cases suggested an incremental efficacy of tocilizumab in severe COVID-19 that were confirmed by subsequent meta-analyses of large randomized trials of tocilizumab. This suggests that analysis of case-control studies and pre-print server data in the early stages of a pandemic appeared robust for supporting incremental benefits and lack of major therapeutic toxicity of tocilizumab for severe COVID-19.

Inflammatory Choroidal Neovascularisation

Inflammatory choroidal neovascularization is uncommon severe sight threatening complication of uveitis, more frequent in posterior uveitis. Hypoxia, release of vascular endothelial growth factor and other mediators seem to be involved in its pathogenesis. Multimodal imaging including the recent optical coherence tomography angiography greatly aid in diagnosis and management. Management of these neovascular membranes consists of anti-vascular growth factor agents, with or without concomitant anti-inflammatory and/or corticosteroid therapy. Besides effective eradication of inflammation in uveitis, the ideal therapeutic goal should include timely detection and treatment of inflammatory CNVM, as the ultimate visual outcome would depend on the control of both

THE SAFETY, TOLERABILITY, AND EFFECTIVENESS OF BIOLOGICS/SMALL MOLECULE THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND CIRRHOSIS

Abstract Introduction Biologic agents and small molecules have been shown to be effective and relatively safe in the treatment of inflammatory bowel disease (IBD). However, data is lacking regarding the use of these agents in patients with IBD and concomitant cirrhosis. The aim of this study is to examine the safety, tolerability and effectiveness of biologics and small molecules in patients with IBD and concomitant cirrhosis. Methods This is a retrospective study of adult patients diagnosed with both IBD and cirrhosis (by liver biopsy or Fibroscan) treated with biologic agents or small molecule agents between 2012 and 2020 within the Yale-New Haven Hospital system. We included patients on tofacitinib or any of the following biologic agents: infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, ustekinumab. Primary outcomes were rates of adverse events (infection, infusion reaction, IBD-related hospitalization) and mortality. Secondary outcomes were clinical remission (defined by the physician global assessment) and mucosal healing (Mayo endoscopic score of 0 or 1 for ulcerative colitis (UC) and absence of erosion/ulcerations in Crohn’s disease (CD)). Results A total of 18 patients (72% CD, 28% UC) with median age of 50 (26–73) years were included (Table 1). Decompensated cirrhosis was present in 33.3% of the population prior to initiation of biologic/small molecule therapy. The most common etiology of cirrhosis was primary sclerosing cholangitis at 38.9%. IBD therapy included: infliximab/adalimumab (44.5%), vedolizumab (27.7%), and ustekinumab (22.2%) and tofacitinib (5.6%). A total of 4 patients (22.2%) were on concomitant corticosteroid therapy and 3 on combination therapy with thiopurines (Table 2). Adverse events occurred in 27.7% (n=5; 1 infusion reaction and 4 infections). The 4 patients with infections included: 2 on infliximab/adalimumab, 1 on ustekinumab, 1 on vedolizumab. Two of these patients were on concomitant thiopurines and 1 on corticosteroid. Biologic therapy was stopped in 3 patients, 2 for non-response and 1 for an infusion reaction. Mortality rate was 11% and all were liver-related. Clinical remission was achieved in 66.7% and mucosal healing was noted in 72.7% (8/11). Conclusions In this cohort of patients with IBD and cirrhosis, biologic/small molecule therapies were effective for IBD. Approximately a quarter of patients experienced adverse events that were mainly due to infections. Larger studies are needed to elucidate the relative safety of different biologic agents and small molecules in IBD patients with cirrhosis.

Impact of topical budesonide on prevention of esophageal stricture after mucosal resection

EMR and endoscopic submucosal dissection (ESD) are treatment modalities for Barrett's esophagus involving high-grade dysplasia or early cancer. Injectional corticosteroid therapy decreases the risk of procedure-related esophageal stricture (ES) formation. Our aim was to assess the efficacy of topical budesonide on the rate of ES formation after EMR or ESD. Patients included prospectively from 3 tertiary endoscopy centers received 3 mg budesonide orally twice a day for 8 weeks after esophageal EMR or ESD of 50% or more of the esophageal circumference between January 1, 2014 and June 30, 2018. These patients were matched (1:3 ratio) retrospectively with a consecutive patient cohort who underwent EMR or ESD of 50% or more of the esophageal circumference without concomitant corticosteroid therapy. The primary endpoint was the presence of ES at the 12-week follow-up. Twenty-five patients (budesonide) were matched with 75 patients (no budesonide). Most underwent EMR for Barrett's esophagus with biopsy-proven high-grade dysplasia or suspected T1a cancer. Although most baseline characteristics did not differ significantly, patients in the budesonide cohort tended to have a higher proportion of circumferential EMR. The proportion of patients with ES was not significantly lower in the budesonide cohort (16% vs 28%). On logistic regression analysis, budesonide remained associated with a lower incidence of ES (P= .023); however, when controlling for baseline characteristics with a propensity score weighted logistic regression model, there was no significant effect on ES formation (P= .176). Topical budesonide might be associated with a reduction of ES after EMR or ESD; however, further studies are needed to verify our results.

Hypogammaglobulinemia after rituximab for rheumatoid arthritis is not rare and is related with good response: 13 years real-life experience.

Rituximab (RTX) use in the treatment of RA can be complicated by decrease in IgG, IgM or IgA levels (hypogammaglobulinemia-HGG). The aim of this study was to define the frequency of HGG in RA patients treated with RTX and to identify associations between its occurrence and patients' characteristics, disease outcomes and serious infections rate. RA patients treated with RTX in two rheumatology centers from January 2007 to January 2020 were retrospectively examined. Demographical, clinical and laboratory parameters were recorded at baseline and at last visit. Eighty-three patients (84.3% females) with a mean age of 63.2 years were enrolled. They had baseline DAS28(CRP) of 5.2 (1.1) and received a median (range) of 8 (2-20) RTX cycles. A total of 43.4%, 24.1% and 31.3% developed 'any HGG', 'low IgG' and 'low IgM', respectively. Lower baseline IgG and IgM levels were predictors of 'low IgG' and 'low IgM' occurrence, respectively. Patients who developed 'low IgM' exhibited lower DAS28(CRP) and increased rates of remission and low disease activity compared with those with normal IgM levels. Patients who maintained normal IgG were receiving methotrexate more frequently. No differences were observed in serious infections rate among subgroups. HGG occurred in 43% of RTX-treated patients. Patients who developed low IgG or low IgM had lower baseline levels than those who did not. Concomitant DMARD and corticosteroid therapy was not associated with HGG. Low IgM, but not low IgG, development was associated with better disease outcomes. HGG was not associated with an increased incidence of serious infections.

Cardiac function at diagnosis is important prognostic factor in patients with cardiac sarcoidosis -from Japanese nationwide questionnaire survey-

Abstract Background Sarcoidosis is a systemic non-caseating granulomatous disease of unknown etiology. Cardiac involvement (cardiac sarcoidosis, CS) has been reported to be an important prognostic factor in this disease because of heart failure and/or ventricular arrhythmia, and corticosteroid therapy is usually prescribed to prevent cardiac events. However, little is known about the relationship of cardiac function and concomitant corticosteroid therapy on later cardiac events in CS. Objective We evaluated the relationship between prognosis and left ventricular ejection fraction (LVEF) at the time of diagnosis in CS patients from the Japanese nationwide questionnaire survey. Methods Total of 757 Japanese patients from 57 hospitals who diagnosed CS were examined. Patients who unsatisfied the criteria of the Japanese new guidelines, or who underwent cardiac transplantations were excluded, and 420 patients (287 females, mean age 60±13 years old, median follow-up periods 1864 days [interquartile range: 845–3159 days]) were analyzed. The relationship of adverse events (all-cause death, cardiovascular death, and appropriate ICD [Implantable Cardioverter Defibrillator] discharge) and LVEF (with corticosteroid 84%) (low LVEF: LVEF≤35% n=98 [with corticosteroid in 78%], moderate LVEF: LVEF 35–50% n=104 [with corticosteroid in 93%], normal LVEF: 50≤LVEF n=218 [with corticosteroid in 83%]) were evaluated respectively. Results 89 CS patients developed all-cause death (n=50), cardiovascular death (n=30) or appropriate ICD discharge (n=48). The frequency of corticosteroid therapy was not different in the each LVEF group, but Kaplan-Meier analysis revealed that all-cause death, cardiovascular death, and all cardiovascular adverse events were more observed in lower LVEF group (log-rank p&amp;lt;0.0001). Furthermore, multivariate Cox hazard analysis revealed that LVEF was a most important independent prognostic factor in CS. Conclusion This Japanese nationwide questionnaire survey data showed that initial LVEF was an independent and strong prognostic predictor in CS, therefore primary prevention would be needed even after starting corticosteroid in patients with decreased cardiac function. Funding Acknowledgement Type of funding source: None

Clinical response among golimumab-treated Japanese patients with rheumatoid arthritis by number of previous biologic therapies: Real-world evidence from post-hoc analysis of post-marketing surveillance data

Objectives To assess the real-world effectiveness of golimumab in Japanese patients with rheumatoid arthritis who had previously received one or more biologic therapies. Methods A post-hoc analysis of post-marketing surveillance was performed. The clinical response to golimumab was analyzed in 1216 patients who had previously received one or more biologic agents including non-TNF inhibitors with stratification by the number of previous biologic agents. Logistic regression analyses were conducted to identify factors associated with DAS28-CRP response to golimumab. Results While treatment persistence is comparable, the response to golimumab declined with an increasing number of previous biologic therapies. When stratified by golimumab dose, patients receiving golimumab at 100 mg had higher disease activity at baseline with an increasing number of previous bDMARDs, but they still achieved comparable disease activity at 24 weeks regardless of how many bDMARDs had been previously used. Univariate and multivariate analyses both identified concomitant oral corticosteroid therapy as a factor negatively associated with the likelihood of achieving a DAS28-CRP response. Conclusion Switching to golimumab was effective regardless of how many biologic agents had been previously used, but the response declined with an increasing number of prior biologic agents. A golimumab dose of 100 mg was also effective for those who previously received three or more bDMARDs.

Systematic Review and Meta-Analysis of Case-Control Studies from 7,000 COVID-19 Pneumonia Patients Suggests a Beneficial Impact of Tocilizumab with Benefit Most Evident in Non-Corticosteroid Exposed Subjects.

Background. Tocilizumab is an anti-IL-6 therapy widely adopted in the management of the so-called “cytokine storm” related to SARS-CoV-2 virus infection, but its effectiveness, use in relationship to concomitant corticosteroid therapy and safety remain unproven. Methods: We performed a systematic review and meta-analysis of case-control studies utilising tocilizumab in COVID-19 on different databases (PubMed/MEDLINE/Scopus) and preprint servers (medRxiv and SSRN) from inception until July 1st 2020 (PROSPERO CRD42020195690). The impact of tocilizumab and concomitant corticosteroid therapy and tocilizumab alone on death rate, need for mechanical ventilation, ICU admission, and bacterial infections were assessed. Subgroup analyses and meta-regressions were performed. Findings: Nineteen studies comprising 7,298 patients (2,377 cases versus 4,921 controls) were included. Therapy including hydroxychloroquine, antivirals, antibiotics and steroids were generally balanced across groups. Tocilizumab use was associated with mortality rate reduction (HR 0.41 ([95%CI 0.25-0.66], p<0.001). Stratifying according to concomitant steroid use which could mask the true effect of tocilizumab, the protective effect was even more highly significant (HR 0.04 [95%CI 0.004-0.35], p<0.001). Reduction in ICU admission (OR 0.16 ([95%CI 0.06-0.43], p<0.001) and in the need for mechanical ventilation (HR 0.49 [95%CI 0.30-0.81], p<0.01; estimate based on 1 study) were significant. Risk of infections was increased (OR 3.11 [95%CI 1.15-8.44], p=0.026; based on unadjusted estimates). Interpretation: Our findings suggest that tocilizumab use can reduce COVID-19 related mortality especially in corticosteroid naive cases but also exerts benefits with concomitant corticosteroid therapy. These findings are immediately relevant for therapy consideration for severe COVID-19 cytokine storm and needs confirmatory future randomized trials.

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received &gt;10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p&gt;0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study.

Background and ObjectiveTendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure.MethodsThe UK Health Improvement Network primary care database was used to perform a nested case–control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated.ResultsCurrent fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25–2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11–4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78–48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures.ConclusionsRisk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.Electronic supplementary materialThe online version of this article (10.1007/s40261-018-0729-y) contains supplementary material, which is available to authorized users.

Prevalence of and risk factors for dermatoporosis: a prospective observational study of dermatology outpatients in a Finnish tertiary care hospital.

Dermatoporosis describes the cutaneous signs and complications related to chronic cutaneous fragility related to ageing, chronic sun exposure and long-term use of topical and systemic corticosteroids. Chronic renal failure may be an additional cofactor. The prevalence of dermatoporosis is estimated around 32-37% in France among the elderly. We evaluated the prevalence of dermatoporosis and its risk factors in outpatients who attended a consultation in the department of dermatology of Helsinki University Central Hospital. A prospective observational study of 176 consecutive outpatients aged 60 years and older, who attended a consultation in the department of dermatology of Helsinki University Central Hospital. Data collection included age, gender, reason for consultation, local or systemic corticosteroid therapy, antiplatelet drugs and anticoagulant therapy, diabetes and chronic kidney failure (glomerular filtration rate < 60 mL/min/m2 ). The presence of dermatoporosis, location on the body and staging were collected. 30.7% presented dermatoporosis. Lesions were mainly located on the upper limbs (94%), and stage I was the most frequent (75.9% of the cases). Multivariate analysis revealed that dermatoporosis was significantly associated with ultrapotent topical corticosteroids (odds ratio (OR) 5.34, 95% CI 1.85-15.43, P = 0.002), oral corticosteroids (OR 3.22, 95% CI 1.18-8.80, P = 0.022), concomitant corticosteroid therapy, anticoagulant and chronic renal failure (OR 4.02, 95% CI 1.34-12.01, P = 0.013) and age (OR 1.05, 95% CI 1.01-1.10, P = 0.016). Patients with bullous pemphigoid were those with the highest prevalence of dermatoporosis in our cohort (64%). Acknowledging the selection bias in our study, the prevalence of dermatoporosis in a dermatology consultation in Finland seems as frequent as in France. These results prompt us to weigh the indications of long-term corticosteroids use in frail elderly patients.

Risk of post‐operative surgical site infections after vedolizumab vs anti‐tumour necrosis factor therapy: a propensity score matching analysis in inflammatory bowel disease

Perioperative vedolizumab (VDZ) and anti-tumour necrosis factor (TNFi) therapies are implicated in causing post-operative complications in inflammatory bowel disease (IBD). To compare the risk of surgical site infections (SSIs) between VDZ- and TNFi-treated IBD patients in propensity-matched cohorts. The Optum Research Database was used to identify IBD patients who received VDZ or TNFi within 30days prior to abdominal surgery between January 2015 and December 2016. The date of IBD-related abdominal surgery was defined as the index date. SSIs were determined by ICD-9/10 and CPT codes related to superficial wound infections or deep organ space infections after surgery. Propensity score 1:1 matching established comparable cohorts based on VDZ or TNFi exposure before surgery based on evidence-based risk modifiers. The propensity-matched sample included 186 patients who received pre-operative biologic therapy (VDZ, n=94; TNFi, n=92). VDZ and TNFi cohorts were similar based on age, gender, IBD type, concomitant immunomodulator exposure, chronic opioid or corticosteroid therapy, Charlson Comorbidity Index and malnutrition. VDZ patients were more likely to undergo an open bowel resection with ostomy. After propensity score matching, there was no significant difference in post-operative SSIs (TNFi 12.0% vs VDZ 14.9%, P=0.56). Multivariable analysis indicated that malnutrition was the sole risk factor for developing SSI (OR 3.1, 95% CI 1.11-8.71) regardless of the type of biologic exposure. In the largest, risk-adjusted cohort analysis to date, perioperative exposure to VDZ therapy was not associated with a significantly higher risk of developing an SSI compared to TNFi therapy.

Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: Effect of sodium naproxen.

To investigate whether topical nonsteroidal antiinflammatory drugs (NSAIDs) are useful, in the absence of concomitant corticosteroid therapy, in limiting postoperative inflammation after uncomplicated cataract surgery. A total of 328 patients were enrolled in a prospective, randomized, double-masked, parallel-group, active-controlled study. Anterior chamber inflammation (ACI) was evaluated as the primary efficacy parameter. Only patients with moderate inflammation (ACI score of <=4) the day after surgery were randomized and treated with NSAIDs. A novel topical formulation containing 0.2% sodium naproxen was compared with 0.1% diclofenac. Both were administered three times a day for 14 consecutive days. Ocular inflammation was measured after 7 and 14 days by using slit-lamp biomicroscopy. Safety parameters were also evaluated at the same time. Both treatments were equally effective in controlling postsurgical inflammation. No statistically significant differences between treatment groups were observed for the safety variables. No serious adverse events (AEs) occurred during the course of the study. The most frequent AE reported with naproxen was eye redness. NSAIDs can effectively be used without concurrent administration of corticosteroids to control postoperative inflammation after uncomplicated cataract surgery. In addition, naproxen ophthalmic solution may be considered a suitable alternative to the currently available NSAIDs. (Eur J Ophthalmol 2005; 15: 598-606).

Partial response of pulmonary adenocarcinoma with symptomatic brain metastasis to nivolumab plus high-dose oral corticosteroid: a case report

BackgroundNivolumab, a monoclonal antibody targeting the programmed death-1 receptor, is indicated in locally advanced or metastatic non-small cell lung cancer, with progression after platinum-based chemotherapy. Up-to-now, few data are available concerning brain activity of this treatment and concomitant use of corticosteroids.Case presentationA 64-year-old caucasian man with a pulmonary adenocarcinoma associated with brain metastases received four courses of nivolumab in concomitance with a high dose of corticosteroids for his neurologic symptoms. He experienced a partial response in his brain and chest with an improvement in his general condition.Nivolumab was effective in shrinking symptomatic brain metastases, and metastases at other sites, in a patient with non-small cell lung cancer and first-line chemotherapy failure. The effect of nivolumab was obtained despite concomitant high-dose corticosteroid therapy. Combined nivolumab and high-dose corticosteroid therapy did not induce unexpected adverse events.ConclusionNivolumab and concomitant high-dose corticosteroid therapy was found to be efficient and well tolerated.