BACKGROUNDThe combination of antitumor necrosis factor-alpha (TNF-α) agents with immunomodulators (IMMs) is a common treatment for pediatric Crohn's disease (CD). Although methotrexate (MTX) can be a first-line medication as an IMM, most clinicians in real-life practice, especially in South Korea, are more familiar with thiopurines. This study aimed to compare the efficacy and immunogenicity of MTX and azathioprine (AZA) as concurrent therapies for pediatric CD.METHODSIn this pilot study, 29 newly diagnosed pediatric patients with moderate-to-severe CD were randomized to receive either MTX (n = 15) (15 mg/body surface area (BSA) per week) or oral AZA (n = 14) (0.5 mg/kg per day) in combination with Infliximab (IFX). The primary outcomes were the proportion of patients in endoscopic, biochemical, and transmural remission after 14 and 54 weeks of IFX therapy. The trough levels (TLs) of IFX and anti-drug antibody (ADA) levels were also compared.RESULTSAmong the 29 patients, there were no significant differences in the biochemical (p = 1.0 at week 14, p = 0.45 at week 54), endoscopic (p = 0.968 at week 14, p = 0.05 at week 54), or transmural (p = 0.103 at week 54) remission rates between the two medications during the concurrent therapy. Additionally, the trends in the IFX trough and ADA levels over time during the treatments were similar for both medications, with no significant differences (p = 0.686, p = 0.389, respectively).CONCLUSIONThe MTX showed comparable efficacy to the AZA in pediatric CD patients with moderate-to-severe disease. This effectively maintained adequate IFX levels and reduced ADA production. Therefore, although additional large-scale clinical trials are needed, this study demonstrated that either MTX or AZA can be selected as IMMs in the concurrent treatment of pediatric CD, depending on individual medical institutions' circumstances.

01 Nov 2022·Journal of Infection

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study

Article

Author: Linley, Ezra ; Harvey, Ruth ; Foulkes, Sarah ; Howell, Michael ; Islam, Jasmin ; Hopkins, Susan ; Semper, Amanda ; Wu, Mary ; Taylor-Kerr, Andrew ; Otter, Ashley D ; Carr, Edward J ; Heeney, Jonathan L ; da Costa, Kelly ; Castillo-Olivares, Javier ; Chan, Andrew ; Hall, Victoria ; Monk, Edward J M ; Milligan, Iain D ; Munro, Katie ; Insalata, Ferdinando ; Zambon, Maria ; Atti, Ana ; Tranquillini, Caio ; Cole, Michelle J ; Brooks, Tim ; Brown, Colin S ; Nadesalingam, Angalee ; Cantoni, Diego ; Hettiarachchi, Nipunadi ; Charlett, Andre ; Hewson, Jacqueline ; Lyall, Jonathan ; Temperton, Nigel ; Chand, Meera A ; Beale, Rupert

OBJECTIVESTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.METHODSWe performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models.RESULTSWe identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40).CONCLUSIONSBefore vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.TRIAL REGISTRATION NUMBERISRCTN11041050.

01 Jan 2014·International Journal of Rheumatology

HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF-α) Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and Meta-Analysis

Review

Author: Leoncini, Emanuele ; Prignano, Francesca ; Panic, Nikola ; Goletti, Delia ; Iannone, Florenzo ; Boccia, Stefania ; Gaeta, Giovanni Battista ; Cantini, Fabrizio

Introduction.Antitumor necrosis factor-alpha (TNF-α) agents are widely used for treatment of rheumatic and dermatological diseases. We conducted the systematic review and meta-analysis to assess the prevalence of HBV reactivation among patients treated with anti-TNF-α.Methods and Findings.A comprehensive literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was conducted. From 21 studies included in the systematic review, 9 included patients with occult chronic HBV infection and 6 included patients with overt infection while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4–8.2%,I2: 74.7%). The pooled prevalence of reactivation was 3.0% (95% CI: 0.6–7.2,I2: 77.1%) for patients with occult infection, and 15.4% (95% CI: 1.2–41.2%,I2: 79.9%) for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1–8.4%,I2: 51.1%) for treatment with etanercept and 4.6% (95% CI: 0.5–12.5%,I2: 28.7%) for adalimumab. For subgroup of patients without any antiviral prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2–8.3%,I2: 75.6%).Conclusion.Although HBV reactivation rate is relatively low in patients treated with anti-TNF-αfor rheumatic and dermatological conditions, the antiviral prophylaxis would be recommended in patients with overt chronic HBV infection.

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