P590 Outcomes of patients treated with sequential anti-TNF therapy in a tertiary referral centre

Abstract Background Anti-TNF agents are administered intravenously(iv) or subcutaneously(SC).Factors such as speed of onset and patient preference influence that decision. The aim of this study was to assess the characteristics and outcomes of patients transitioned between iv and sc anti-TNF therapy. Methods Patients attending a single tertiary referral centre, treated with two different anti-TNF drugs were included. Patient and disease characteristics, biochemical, endoscopic and radiological data were collated. Results 69 patients were included. Table 1 describes the patient cohort. 28 (40.6%) patients transitioned from SC anti-TNF to infliximab (IFX). N=35 (50.7%) switched from IFX to Adalimumab and 6 to Golimumab. 31 patients demonstrated some degree of endoscopic activity prior to anti-TNF switch;14/16 (87.5%) demonstrated radiological activity. 48 patients had endoscopic assessment post-switch; 28 (58.3%) had endoscopic remission.Of the 19 patients with post-transition imaging, 42.1% (8/19) had no active disease. 43 (79.6%) patients had therapeutic trough concentrations of the current anti-TNF. 13 (26%) were previously on combination therapy, while 22 (32.8%) currently are. 24 (39.3%) patients had detectable anti-drug antibodies to their prior anti-TNF, 10 (16.4%) had primary non-response and 12 (19.7%) had loss of response with adequate drug levels. There were significantly more patients with antibody formation in the group switching from IFX to SC anti-TNF (n = 20; p = 0.001). A significantly higher proportion of patients who were transitioned from IFX to SC anti-TNF currently have therapeutic/supratherapeutic drug levels when compared with patients transitioning SC to IFX (p = 0.01). There is no significant difference in the proportion currently on combination therapy (p = 0.668). There is a significant improvement in c-reactive protein, albumin and haemoglobin in the cohort as a whole. However, there is no significant difference in rates of clinical remission (p = 0.556) or endoscopic remission (p = 0.89) after switching from one mode of delivery to another. Conclusion Patients converted from IFX to SC anti-TNF have similar rates of endoscopic and clinical remission to those transitioned to IFX. However, many patients had previous antibody formation. Subsequently, this group has significantly higher rates of therapeutic or supra-therapeutic drug concentrations, suggesting the conscientious use of therapeutic drug monitoring to optimise response.

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The Prognostic Significance of Monoallelic Versus Biallelic 13q Deletions in Patients with Chronic Lymphocytic Leukemia,

Blood ◽

10.1182/blood.v118.21.3893.3893 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3893-3893

Author(s):

Smita Sinha ◽

Timothy W Farren ◽

Marianne Grantham ◽

Samir Agrawal

Keyword(s):

Overall Survival ◽

Lymphocytic Leukemia ◽

Referral Centre ◽

Tertiary Referral ◽

Interphase Nuclei ◽

Tertiary Referral Centre ◽

Cytogenetic Abnormalities ◽

Significant Difference ◽

13Q Deletion

Abstract Abstract 3893 Introduction: 13q deletions (13q-) are the commonest cytogenetic abnormality observed in patients with chronic lymphocytic leukemia as detected by fluorescence in situ hybridization (FISH). It has been observed in 45–55% of patients; in 30% it is the sole cytogenetic abnormality and in this context confers a favourable prognosis. However recent studies highlight that the situation may be more complex, with suggestions that the percentage of interphase nuclei with deletions, and the size of the deletion are key determinants of prognosis. Additionally it remains to be established whether the presence of a homozygous versus a heterozygous 13q deletion plays an additional role. Initial reports suggest that heterozygosity does not impact on time to first treatment or overall survival. Methods: We present the results of 247 patients referred to St BartholomewÕs Hospital, a tertiary referral centre, between 2002 and 2010. Diagnostic specimens were sent including cytogenetic analysis, with a proportion also referred for clinical management. Patients referred only for cytogenetic analysis were excluded from the time to treatment (TTT) and survival data. Between August 2002 and December 2010, 247 samples were found to have a 13q deletion. Samples included both peripheral blood and bone marrow. Duplicate patient samples were excluded. The probes used were Abbott Molecular IGH@/CCND1 dual colour dual fusion, Abbott Molecular Vysis LSI p53 / LSI ATM and LSI D13S319 / LSI 13q34 / CEP 12 Multi-color or the Cytocell Aquarius CLL Screening Panel. Results: Interphase FISH detected a monoallelic deletion in 133 patients (53.8%) and biallelic in 32 cases (13%). Mosaics of mono- and biallelic deletions within the nuclei were detected in 32 cases (13%). 50 cases (20.2%) demonstrated 13q deletion in addition to other cytogenetic abnormalities. 145 of the 247 patients were managed clinically at St BartholomewÕs Hospital either as the sole centre or in conjunction with their referring hospital. Seventy-eight of the 145 patients had a monoallelic 13q-, in which 38 cases (48.7%) required therapy, with a median TTT of 70.6 months. 12 patients had a sole biallelic deletion. In contrast, of those patients with a biallelic 13q-, 75% required therapy with a significantly shorter TTT (21.9 months, p=0.0284, figure 1). There were 10 deaths within the monoallelic 13q- cohort with a median follow up time of 31 months. For those with bi13q-, three deaths occurred with a median follow up of 17 months. Nineteen patients had a mosaic of monoallelic and biallelic deletions in their nuclei. Thirteen required treatment with a TTT of 56.6 months, with 3 patient deaths. Median follow up was 42 months. Of the remaining 36 patients with additional cytogenetic abnormalities, 28 (78%) required treatment with a TTT of 24 months, in which 15 patients died (median follow up: 16 months). This group was further characterized; 19 patients had an additional 11q22 deletion, which was the commonest abnormality. Nine patients had an additional 17p13 deletion and six had trisomy 12. The remaining 8 cases were either a combined 17p13- and 11q22- or 11q13-. Conclusion: Two recent studies (171i and 323ii patients) failed to demonstrate a significant difference in TTT and overall survival between patients with a heterozygous and homozygous 13q deletion. In this study, we demonstrated a significant difference in TTT (p=0.0004) amongst the patient subgroups, specifically patients with monoallelic 13q versus biallelic deletions (p=0.0284). Patients with additional cytogenetic abnormalities had the shortest TTT. This group contained patients with 17p deletions that formed 25% of the subgroup. All patient cohorts are currently being characterized further according to age, Rai/Binet stage, CD38 expression, ZAP70 expression, IgH mutational status and percentage of interphase nuclei deleted. As a tertiary referral centre, cases managed at St BartholomewÕs Hospital are skewed towards complex or refractory patients. Whilst patient numbers collated are small, they appear to suggest that a biallelic deletion confers a negative impact on TTT and that 13q deletions may not uniformly represent a good prognostic marker. Disclosures: No relevant conflicts of interest to declare.

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P718 Combination therapy of adalimumab with an immunomodulator is not more effective than adalimumab monotherapy in children with Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.846 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S578-S579

Author(s):

M Matar ◽

R Shamir ◽

D Turner ◽

E Broide ◽

B Weiss ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Combination Therapy ◽

Clinical Remission ◽

Controlled Trial ◽

Combination Group ◽

Therapeutic Drug ◽

Monotherapy Group ◽

Serious Adverse Events ◽

Significant Difference

Abstract Background The PAILOT trial was a randomised controlled trial aimed to evaluate proactive vs. reactive therapeutic drug monitoring in children with Crohn’s disease (CD) treated with adalimumab. Our aim, in this post-hoc analysis of the PAILOT trial, was to assess the efficacy and safety of adalimumab combination treatment in comparison to monotherapy at week 72 after adalimumab induction. Methods Participants were children 6–17 years old, biologic naïve, with moderate-to-severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline, maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit patients were assessed for disease index, serum biomarkers, faecal calprotectin, adalimumab trough concentration and anti-adalimumab antibodies. Results Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period there was no significant difference in the rates of sustained corticosteroid free clinical remission (25/34, 73% vs. 28/44, 63%; p = 0.35), and sustained composite outcome of clinical remission, CRP≤0.5 mg/dl and calprotectin≤150 µgr/gr (10/34, 29% vs. 14/44, 32%; p = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive sub-groups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but numerically higher in the monotherapy group. Conclusion Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD.

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Impact of the COVID-19 pandemic on acute otolaryngology inpatient activity at a tertiary referral centre: a retrospective analysis.

10.22541/au.163250559.92665020/v1 ◽

2021 ◽

Author(s):

Praveena Deekonda ◽

Adal Mirza ◽

Huw Jones

Keyword(s):

Age Groups ◽

Neck Surgery ◽

Referral Centre ◽

Tertiary Referral ◽

Tertiary Referral Centre ◽

Admission Rates ◽

Significant Difference ◽

Surgery Department ◽

The Impact ◽

Overall Mortality

Objective To determine the impact of the COVID-19 pandemic on acute admissions and inpatient activity at a tertiary referral centre. Design Retrospective review of coding-based inpatient electronic records. Setting An otolaryngology and head and neck surgery department at a UK major trauma and tertiary referral centre. Participants Otolaryngology patients admitted as an emergency over a period of 12 months pre-COVID19 (01/04/2019-31/03/2020) and 10 months post-COVID19 (01/04/2020-23/01/2021). Main outcome measures Baseline characteristics, admission rates, length of stay (LoS), overall mortality and 30-day mortality. Results 1844 records were reviewed; (1293 pre-COVID19, 551 post-COVID19). Admissions across all age groups were reduced, with an increase in mean age from 40.4 to 47.4 years (p=0.001). LoS remained unchanged (3.74 vs 3.82 days, p=0.251). Epistaxis remained the most common presentation, with an increased LoS compared to the pre-COVID19 cohort. GP referrals reduced from 18.0% to 4.2% (n=233 vs n=23, p<0.001) and ED referrals proportionally increased from 60.9% to 75.3%, n=787 vs n=417, p<0.001). Critical care admissions were higher in the post-COVID19 cohort (OR 1.82 (1.11-2.99) [95% CI], p=0.017). There was no significant difference in overall mortality between groups (n=74, 5.7% vs. n=33, 6.0%; p=0.844). Thirty-day mortality increased from 0.9% (n=12) pre-COVID19 to 2.3% (n=13) post-COVID19 (p=0.03). Conclusions This study demonstrates significant changes and a reduction in acute otolaryngology presentations. Our findings suggest that sicker, frailer patients were admitted during the pandemic. This study highlights important considerations for acute otolaryngology care moving forward after the pandemic.

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