ABSTRACT
Background The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this , we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs. Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates. Conclusion No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this as this might negatively impact the current submission process.
ABSTRACT
Introduction Objective evaluation of treatment response is the gold standard in ulcerative colitis (UC). In this setting, intestinal ultrasound (IUS) is a non-invasive alternative to endoscopy. Recent studies showed change in IUS parameters after treatment initiation but studies with an endoscopic reference standard are scarce. The aim of this study was to evaluate early change of IUS parameters and determine cut-off values for endoscopic endpoints in UC patients starting anti-inflammatory treatment. Methods In this longitudinal prospective study consecutive patients with moderate-severe UC (baseline endoscopic Mayo score (EMS)≥2) starting an anti-inflammatory treatment were included. Clinical scores, biochemical parameters and IUS parameters were collected at baseline, after 2 (T1), 6 (T2) and 8-26 weeks (T3) around time of the second sigmoidoscopy/colonoscopy. Bowel wall thickness (BWT), Colour Doppler signal (CDS), haustrations, inflammatory fat and wall layer stratification were measured as previously established1. Endoscopic remission (ER) and mucosal healing (MH) were evaluated in the sigmoid and defined as EMS=0 and EMS≤1, respectively. The ultrasonographist and endoscopist were blinded for the outcomes of endoscopy and IUS, respectively. Results 51 consecutive patients were included (Table 1) of whom 31 underwent a second endoscopy. Two additional patients underwent colectomy and were considered non-responders. 18 patients did not undergo second endoscopy due to the COVID-19 pandemic (n=2), refusal (n=5), loss to follow-up (n=1) or treatment escalation because of clinical deterioration confirmed by IUS and biomarkers before second endoscopy was performed (n=10). BWT was significantly lower from T2 onwards in patients reaching MH (p=0.026) and ER (p=0.002) at T3 (Fig 1). A significant decrease in BWT was already visible at T1 in patients receiving infliximab (median DBWT T0-T1: -26% [-43% - -6%], p=0.001) or tofacitinib (median ∆BWT T0-T1: -33% [-46% - -5%], p=0.001) but not in patients treated with vedolizumab (median ∆BWT T0-T1: -14% [-43% - 5%], p=0.11). Most accurate BWT cut-off values at T3 to determine MH and ER were 3.52 mm (AUROC: 0.95, 95% CI: 0.86-1.00, p<0.0001, sens:91%, spec:91%) and 2.98 mm (AUROC: 0.94, 95% CI: 0.85-1.00, p=0.001, sens:87%, spec:100%), respectively. At T2, BWT per 1 mm increase and CDS were inversely associated with MH (BWT: OR: 0.48 (0.24-0.96, p=0.038);CDS: OR 0.16 (0.03-0.83), p=0.028) and ER (BWT: OR: 0.30 (0.11-0.76), p=0.01). Conclusion BWT and CDS 6 weeks after start of treatment could predict MH and ER. In addition, treatment response at IUS is drug-specific. Furthermore, we have provided accurate BWT cut-off values for endoscopic outcomes. In a point-of-care setting, (early) treatment evaluation with IUS could guide treatment decision in UC in order to optimize treatment response. 1. Bots et al. JCC 2021
ABSTRACT
Background: Objective evaluation of treatment response is the gold standard in ulcerative colitis (UC). In this setting, intestinal ultrasound (IUS) is a non-invasive alternative to endoscopy. Recent studies showed change in IUS parameters after treatment initiation but studies with an endoscopic reference standard are scarce. The aim of this study was to evaluate early change of IUS parameters and determine cut-off values for endoscopic endpoints in UC patients starting anti-inflammatory treatment. Methods: In this longitudinal prospective study consecutive patients with moderate-severe UC (baseline endoscopic Mayo score (EMS)≥2) starting an anti-inflammatory treatment were included. Clinical scores, biochemical parameters and IUS parameters were collected at baseline, after 2 (T1), 6 (T2) and 8-26 weeks (T3) around time of the second sigmoidoscopy/colonoscopy. IUS parameters were measured as previously established1. Endoscopic remission (ER) and mucosal healing (MH) were evaluated in the sigmoid and defined as EMS=0 and EMS≤1, respectively. The ultrasonographist and endoscopist were blinded for the outcomes of endoscopy and IUS, respectively. Results: 51 consecutive patients were included (Table 1) of whom 31 underwent a second endoscopy (MH: n=15 (45%), ER: n=9 (27%)). Two additional patients underwent colectomy and were considered non-responders. 18 patients did not undergo second endoscopy due to the COVID-19 pandemic (n=2), refusal (n=5), loss to follow-up (n=1) or treatment escalation because of clinical deterioration confirmed by IUS and biomarkers before second endoscopy was performed (n=10). Bowel wall thickness (BWT) was significantly lower from T2 onwards in patients reaching MH (p=0.026) and ER (p=0.002) at T3 (Fig 1). A significant decrease in BWT was already visible at T1 in patients receiving infliximab (p=0.001) or tofacitinib (p=0.007), but not in patients treated with vedolizumab (p=0.11) (Fig 2). Most accurate BWT cut-off values at T3 to determine MH and ER were 3.52 mm (AUROC: 0.95, 95% CI: 0.86-1.00, p<0.0001, sens: 91%, spec: 91%) and 2.98 mm (AUROC: 0.94, 95% CI: 0.85-1.00, p=0.001, sens: 87%, spec: 100%), respectively. Other IUS parameters at T3 did not improve association with MH or ER. IUS parameters at T2 that predict MH and ER are demonstrated in Table 2. Conclusion: BWT and Colour Doppler Signal 6 weeks after start of treatment are associated with and could predict MH and ER. In addition, treatment response patterns at IUS are drug-specific. Furthermore, we have provided accurate BWT cut-off values for endoscopic outcomes. In a point-of-care setting, (early) treatment evaluation with IUS could guide treatment decision in UC in order to optimize treatment response.
ABSTRACT
OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.