Antibodies to Human Recombinant Lipocortin-L in Inflammatory Bowel Disease

1993 ◽  
Vol 84 (4) ◽  
pp. 381-386 ◽  
Author(s):  
T. R. J. Stevens ◽  
S. F. Smith ◽  
D. S. Rampton
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Clinical Response ◽  
Corticosteroid Therapy ◽  
Bowel Disease ◽  
Corticosteroid Withdrawal ◽  
Inflammatory Bowel ◽  
Antibody Levels

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease. The low levels of IgM lipocortin-I antibody in patients undergoing long-term corticosteroid therapy (steroid nonresponders) contrasts with previous findings in patients with rheumatoid arthritis and might reflect corticosteroid-induced antibody suppression and/or depressed production of endogenous lipocortin-I antigen.

Tacrolimus induces short-term but not long-term clinical response in inflammatory bowel disease

2020 ◽  
Vol 51 (9) ◽  
pp. 870-879 ◽  
Author(s):  
Iago Rodríguez-Lago ◽  
Jesús Castro-Poceiro ◽  
Agnès Fernández-Clotet ◽  
Francisco Mesonero ◽  
Antonio López-Sanromán ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Response ◽  
Bowel Disease ◽  
Short Term ◽  
Inflammatory Bowel

scholarly journals P695 Vedolizumab induction and maintenance though levels and long-term clinical and biochemical status in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S563-S564
Author(s):  
A Gutiérrez Casbas ◽  
L Sempere Robles ◽  
R Muñoz Pérez ◽  
A Rodríguez Angulo ◽  
S Climent ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Response ◽  
Bowel Disease ◽  
Induction Phase ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Inflammatory Bowel ◽  
Biochemical Remission

Abstract Background Therapeutic drug monitoring (TDM) postinduction of vedolizumab (VDZ) could have relationship with long-term outcome of inflammatory bowel disease (IBD) patients. However, clinical utility of TDM during maintenance VDZ therapy remains unclear. To examine the association of induction and maintenance vedolizumab though levels (VTL) with clinical and biochemical long-term outcome in IBD patients. Methods We performed a retrospective cohort study, including all consecutive IBD patients of our centre on VDZ treatment who had VTL and anti-vedolizumab antibodies (AVA) measured during induction and maintenance therapy. All patients had received a minimum of 6 weeks therapy following standard induction (0, 2, 6 ± 10 week dosing. Clinical response and remission were defined by Partial Mayo Score (PMS, UC) or Harvey Bradshaw Index (HBI, CD) and were assessed at week 52.Biochemical remission was defined as CRP < 0.5 g/dl and faecal biomarker remission as faecal calprotectin (FC) < 250 µg/g. Measurement of VTL and AVA was performed by ELISA assays(Vedolizumab-TheraDiag(R) with a detection limit for VTL of 2 μg/ml and measurement range of 2–60 μg/ml. Results In total, 34 patients were included (55.9% UC; 44.1% CD, 50% women). Median age was 52.76(17–83) and mean disease duration was 8 ± 7.2 years. Median baseline HBI was 6(0–12) and PMS was 5(3–7). FC and CRP measured before first dose of VDZ were 1425 ± 1189 μg/g and 2.1 ± 2.4 mg/dl. A total of 14 patients (41.2%) were naïve for biologic therapy. Only three patients (8.8%) were receiving a concomitant immunomodulator. Clinical response to induction phase was reported in 76%. Clinical remission, clinical response, biochemical remission and faecal biomarker remission were present in 30% (9/29), 41.4% (12/29), 40.9% (9/22) and 35% (7/20), respectively, at week 52. Thirteen patients (13/26, 50%) needed dose escalation at week 52. Twenty-six patients (78.8%) were persistent in VDZ therapy at the end of the study. The median level of VDZ at weeks 6 and 24 were 16.13 ± 7.06 μg/ml and 9.6 ± 6.7 μg/ml. Comparing patients with and without clinical response or remission to VDZ at week 52 no significant difference in VTL was found at Week 6 (16.27 vs. 15.46 μg/ml, p = 0.8) and week 24 (7.6 vs. 12.7 μg/ml, p = 0.1). No difference was observed in VTL in patients in biochemical remission (week 6: 23.6 vs. 15.7 μg/ml, p = 0.2; week 24: 10.3 vs. 10.2 μg/ml, p = 0.9) or with faecal biomarker remission (week 6: week 6: 25.5 vs. 16.2 μg/ml, p = 0.1; week 24: 10.7 vs. 8.2 μg/ml, p = 0.6) at week 52. No patient developed antibodies. Conclusion In this real-world study of IBD patients receiving VDZ, early induction or maintenance VTL are not associated with long-term outcome.

scholarly journals Long-term effectiveness, safety and immunogenicity of the biosimilar SB2 in inflammatory bowel disease patients after switching from originator infliximab

2021 ◽  
Vol 14 ◽  
pp. 175628482098280
Author(s):  
Sarah Fischer ◽  
Sarah Cohnen ◽  
Entcho Klenske ◽  
Heike Schmitt ◽  
Francesco Vitali ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Serious Adverse Events ◽  
Mayo Score ◽  
Normal Ranges ◽  
Inflammatory Bowel ◽  
The Individual

Background: Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. Methods: This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn’s disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. Results: One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months’ (range 2–110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was −0.9 (SD 2.6), –0.4 (2.2) and –0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3–12.2), 5.0 µg/ml (2.7–10.0), 6.6 µg/ml (3.5–12.4) and 5.1 µg/ml (2.7–10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85–0.95), 79% (0.72–0.86), 72% (0.64–0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. Conclusion: Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.

scholarly journals P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S466-S467
Author(s):  
S Fischer ◽  
S Mesfin ◽  
E Klenske ◽  
H Schmitt ◽  
F Vitali ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Patient Visit ◽  
Serious Adverse Events ◽  
Inflammatory Bowel

Abstract Background SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients. Methods This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit. Results A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses). Conclusion Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.

scholarly journals Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ahmed B. Bayoumy ◽  
Elsa L. S. A. van Liere ◽  
Melek Simsek ◽  
Ben Warner ◽  
Aathavan Loganayagam ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
United Kingdom ◽  
Adverse Events ◽  
Clinical Response ◽  
Bowel Disease ◽  
Multi Centre Study ◽  
The United Kingdom ◽  
Inflammatory Bowel

Abstract Background Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. Methods A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. Results A total of 193 patients (57% female and 64% Crohn’s disease) were included, with a median daily TG dose of 20 mg (range: 20–40 mg), a median treatment duration of 23 months (IQR 10–47) and a median follow-up of 36 months (IQR 22–53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145–1761) and 47 mu/L (IQR 34.5–96). Conclusions Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.

scholarly journals Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BiKeR registry

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Giulia Armaroli ◽  
Ariane Klein ◽  
Gerd Ganser ◽  
Michael J. Ruehlmann ◽  
Frank Dressler ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Continuous Treatment ◽  
Inactive Disease ◽  
Minimal Disease Activity ◽  
Serious Infections ◽  
Inflammatory Bowel ◽  
Minimal Disease

Abstract Background At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). Methods JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 to March 2019, and baseline characteristics, effectiveness, and safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, and ACR-inactive disease definition. Safety assessments were based on adverse event (AE) reports. Results A total of 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug, and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after nine years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p = 0.3] and 52 SAEs (1.4/100PY; p = 0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p = 0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p = 0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p = 0.015) for inflammatory bowel disease, and 1.9/100PY and 1.4/100PY (p = 0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. Conclusions No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.

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