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1.
Clin Drug Investig ; 42(6): 477-489, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1878006

ABSTRACT

Subcutaneous infliximab recently received approval for the treatment of various immune-mediated inflammatory diseases in Europe, following pivotal clinical trials in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab demonstrated an improved pharmacokinetic profile compared with intravenous infliximab: the more stable exposure and increased systemic drug concentrations mean it has been cited as a biobetter. Alongside the pharmacokinetic advantages, potential benefits for efficacy, immunogenicity, and health-related quality-of-life outcomes have been suggested with subcutaneous infliximab. During the coronavirus disease 2019 pandemic, the benefits of subcutaneous over intravenous therapies became apparent: switching from intravenous to subcutaneous infliximab reduced the hospital visit-related healthcare resource burden and potential viral transmission. Clinical advantages observed in pivotal trials are also being seen in the real world. Accumulating experience from four European countries (the UK, Spain, France, and Germany) in patients with rheumatic diseases and inflammatory bowel disease supports clinical trial findings that subcutaneous infliximab is well tolerated, increases serum drug concentrations, and offers maintained or improved efficacy outcomes for patients switching from intravenous infliximab. Initial evidence is emerging with subcutaneous infliximab treatment after intravenous infliximab failure. High patient satisfaction and pharmacoeconomic benefits have also been reported with subcutaneous infliximab. Treatments aligned with patient preferences for the flexibility and convenience of at-home subcutaneous administration could boost adherence and treatment outcomes. Altogether, findings suggest that switching from intravenous to subcutaneous infliximab could be advantageous, and healthcare professionals should be prepared to discuss supporting data as part of shared decision making during patient consultations.


The tumor necrosis factor inhibitor infliximab is one treatment option that may be appropriate for patients with immune-mediated inflammatory diseases. Patients may prefer tumor necrosis factor inhibitors administered via the subcutaneous (SC) or intravenous (IV) route, with preferences influencing treatment satisfaction and outcomes. In 2019, CT-P13 SC became the first SC infliximab product to receive regulatory approval in Europe, based on pivotal clinical studies that compared SC infliximab to IV infliximab in patients with rheumatoid arthritis and inflammatory bowel disease. Subcutaneous infliximab is now approved in Europe for the treatment of adults with rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Patients began to switch from IV to SC infliximab outside clinical trials in March 2020, during the coronavirus disease 2019 pandemic. Switching from IV to SC infliximab allowed patients to self-administer treatment at home rather than attend hospital for infusions, reducing potential hospital-acquired infections and lessening the strain on healthcare systems during the pandemic. Clinical trial evidence and growing real-world experience demonstrate that SC infliximab offers clinical advantages in terms of an improved pharmacokinetic profile and potential efficacy, immunogenicity, and health-related quality-of-life benefits compared with IV infliximab. Patients have also reported increased satisfaction with SC infliximab after switching from IV infliximab. Together with the long-standing flexibility and convenience benefits of SC administration, the clinical advantages of SC infliximab make it a valid therapeutic option for rheumatoid arthritis and inflammatory bowel disease. This warrants discussion with appropriate patients as part of shared treatment decision making.


Subject(s)
Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , COVID-19 , Inflammatory Bowel Diseases , Antibodies, Monoclonal/adverse effects , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , COVID-19/drug therapy , Humans , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Treatment Outcome
2.
Immun Inflamm Dis ; 10(6): e628, 2022 06.
Article in English | MEDLINE | ID: covidwho-1850063

ABSTRACT

BACKGROUND AND OBJECTIVE: Despite the pervasive vaccination program against coronavirus disease 2019 (COVID-19), fully vaccinated people are still being infected by severe acute respiratory syndrome coronavirus 2, making an effective and safe therapeutic intervention a crucial need for the patients' survival. The purpose of the present study is to seek available evidence for the efficacy and safety of three promising medications artesunate, imatinib, and infliximab against COVID-19. METHODS: A literature search was conducted in PubMed, Cochrane Library, medRxive, and Google Scholar up to January 2022. Furthermore, the clinical trial databases were screened to find more citations. The Cochrane Collaboration tool and Newcastle-Ottawa scale were used to assess the included studies. Meta-analysis was performed using RevMan 5.4.1. RESULTS: Five published studies were identified as eligible. Meta-analysis showed that there was no significant difference between the infliximab and control groups in terms of mortality rate (risk ratio [RR]: 0.65; 95% confidence interval [CI]: 0.40-1.07; p = 0.09). However, a significant difference was observed between the two groups for the hospital discharge (RR: 1.37; 95% CI: 1.04-1.80; p = 0.03). No remarkable clinical benefit was observed in favor of using imatinib for COVID-19 patients. Artesunate showed significant improvement in patients with COVID-19. CONCLUSION: In the present, limited evidence exists for the efficacy and safety of artesunate, imatinib, and infliximab in patients with COVID-19. The findings of WHO's Solidarity international trial will provide further information regarding these therapeutic interventions.


Subject(s)
COVID-19 , Artesunate/therapeutic use , COVID-19/drug therapy , Humans , Imatinib Mesylate , Infliximab/therapeutic use , SARS-CoV-2
3.
Clin Transl Gastroenterol ; 13(4): e00484, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1766185

ABSTRACT

Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , COVID-19/prevention & control , COVID-19 Vaccines , Chronic Disease , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/pharmacology , Infliximab/therapeutic use , SARS-CoV-2
4.
Nat Commun ; 13(1): 1379, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1747222

ABSTRACT

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Viral Vaccines , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Vaccines , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2 , T-Lymphocytes , Tumor Necrosis Factor Inhibitors
5.
J Infect Chemother ; 28(6): 814-818, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1649662

ABSTRACT

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab. A Japanese boy who was diagnosed with coronavirus disease 2019 (COVID-19) before a month developed MIS-C with fulfilling six principal symptoms of KD. Laboratory data showed extreme hyperferritinemia (11,404 ng/mL), besides lymphopenia and thrombocytopenia. The patient was refractory to initial therapy with intravenous immunoglobulin (IVIG; 2 g/kg), aspirin, and prednisolone. He was therefore administered a second IVIG (2 g/kg) and infliximab (5 mg/kg) on days 7 and 8 from the onset of fever, respectively, which resulted in an improvement of clinical symptoms. Only four Japanese cases with MIS-C were reported and all of them were responsive to IVIG. The hyperferritinemia in this case was distinctive from previously reported MIS-C cases in Japan and other cohorts and may be associated with refractoriness to IVIG therapy. Marked elevation of circulating ferritin levels is known to be induced by tumor necrosis factor-α, which plays a key role in the pathogenesis of both KD and MIS-C. Thus, for MIS-C patients with hyperferritinemia, early intervention with adjunctive infliximab may induce a more rapid resolution of inflammation and improve outcome. Because MIS-C may be heterogeneous with respect to immunopathology, genetic background, clinical phenotypes and response to therapies, optimized treatment strategies according to immunopathogenesis are required.


Subject(s)
COVID-19 , Connective Tissue Diseases , Hyperferritinemia , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , COVID-19/drug therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Infliximab/therapeutic use , Japan , Male , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/drug therapy
6.
Sci Rep ; 12(1): 465, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1627057

ABSTRACT

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients' clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.


Subject(s)
Polychondritis, Relapsing/complications , Polychondritis, Relapsing/drug therapy , Respiratory Tract Diseases/etiology , Adult , Azathioprine/therapeutic use , Cross-Sectional Studies , Cyclophosphamide/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Infliximab/therapeutic use , Japan/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Polychondritis, Relapsing/epidemiology , Polychondritis, Relapsing/mortality , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/mortality , Retrospective Studies , Surveys and Questionnaires
7.
Adv Ther ; 39(6): 2342-2364, 2022 06.
Article in English | MEDLINE | ID: covidwho-1607755

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patients to self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is the first SC formulation of infliximab that received regulatory approval and may be termed a biobetter as it offers significant clinical advantages over intravenous (IV) infliximab, including improved pharmacokinetics and a convenient mode of delivery. Potential benefits in terms of reduced immunogenicity have also been suggested. With a new SC formulation, infliximab provides an additional option for dual formulation, which enables patients to transition from IV to SC administration route without changing agent. Before COVID-19, clinical trials supported the efficacy and safety of switching from IV to SC infliximab for patients with rheumatoid arthritis and inflammatory bowel disease (IBD), and SC infliximab may have been selected on the basis of patient and HCP preferences for SC agents. During the pandemic, patients with rheumatic diseases and IBD have successfully switched from IV to SC infliximab, with some clinical benefits and high levels of patient satisfaction. As patients switched to SC therapeutics, the reduction in resource requirements for IV infusion services may have been particularly welcome given the pandemic, facilitating reorganisation and redeployment in overstretched healthcare systems, alongside pharmacoeconomic benefits and a reduction in exposure to nosocomial infection. Telemedicine and contactless healthcare have been pushed to the forefront during the pandemic, and a lasting shift towards remote patient management and community/home-based drug administration is anticipated. SC infliximab supports the implementation of this paradigm for future improvements of healthcare value delivered. The accumulation of real-world data during the pandemic supports the high level of confidence, with patients, physicians, and healthcare systems benefitting from its uptake.


Subject(s)
Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , COVID-19 , Cross Infection , Inflammatory Bowel Diseases , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Treatment Outcome
8.
Lancet Respir Med ; 10(3): 255-266, 2022 03.
Article in English | MEDLINE | ID: covidwho-1586183

ABSTRACT

BACKGROUND: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. METHODS: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. FINDINGS: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment-time interactions were -0·09 (95% CI -0·19 to 0·00) for namilumab and 0·06 (-0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. INTERPRETATION: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation-as measured by CRP concentration-in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. FUNDING: Medical Research Council.


Subject(s)
COVID-19 , Adolescent , Antibodies, Monoclonal, Humanized , Bayes Theorem , COVID-19/drug therapy , Humans , Infliximab/therapeutic use , SARS-CoV-2 , Standard of Care , Treatment Outcome
9.
Viruses ; 13(11)2021 10 24.
Article in English | MEDLINE | ID: covidwho-1481024

ABSTRACT

Vaccines to prevent the impact of SARS-CoV-2 are now available, including for patients with autoimmune diseases. However, there is no information about how inflammatory bowel disease (IBD) treatment could impact the cellular and humoral immune responses. This study evaluated SARS-CoV-2-specific humoral and cellular responses after vaccination with a two-dose schedule in a Crohn's disease patient treated with Infliximab (10 mg/kg); we included comparisons with a monozygotic twin. The results showed that the Crohn's disease's twin (twin 2) had no antibody detection and reduced activation of CD4+ T cell responses, unlike the twin without the autoimmune disease (twin 1). Twin 2 developed antigen-specific central memory CD8+ T-cells and IFNγ production after the second dose of COVID-19 vaccination, similar to twin 1. These findings elucidated the role of T-cell immunity after COVID-19 immunization on IBD patients despite the lack of antibody production. Finally, our observation supports the consensus recommendation for IBD patients to receive COVID-19 vaccines.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Crohn Disease/immunology , Lymphocyte Activation , /immunology , Adult , Antibodies, Viral/blood , Crohn Disease/drug therapy , Female , Humans , Immunity, Humoral , Infliximab/therapeutic use , Interferon-gamma/analysis , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Twins, Monozygotic
10.
J Cell Biochem ; 123(2): 155-160, 2022 02.
Article in English | MEDLINE | ID: covidwho-1473858

ABSTRACT

Drug repurposing is an attractive option for identifying new treatment strategies, in particular in extraordinary situations of urgent need such as the current coronavirus disease 2019 (Covid-19) pandemic. Recently, the World Health Organization announced testing of three drugs as potential Covid-19 therapeutics that are known for their dampening effect on the immune system. Thus, the underlying concept of selecting these drugs is to temper the potentially life-threatening overshooting of the immune system reacting to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This viewpoint discusses the possibility that the impact of these and other drugs on autophagy contributes to their therapeutic effect by hampering the SARS-CoV-2 life cycle.


Subject(s)
Antiviral Agents/pharmacology , Artesunate/pharmacology , Autophagy/drug effects , COVID-19/drug therapy , Drug Repositioning , Imatinib Mesylate/pharmacology , Infliximab/pharmacology , Pandemics , SARS-CoV-2/drug effects , Antidepressive Agents/pharmacology , Antiviral Agents/therapeutic use , Artesunate/therapeutic use , Chloroquine/pharmacology , Drug Development , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/physiology , Endoplasmic Reticulum/virology , Endosomes/drug effects , Endosomes/virology , Humans , Hydroxychloroquine/pharmacology , Imatinib Mesylate/therapeutic use , Infliximab/therapeutic use , Intracellular Membranes/drug effects , Intracellular Membranes/physiology , Intracellular Membranes/virology , Ivermectin/pharmacology , Macrolides/pharmacology , Middle East Respiratory Syndrome Coronavirus/drug effects , Niclosamide/pharmacology , Niclosamide/therapeutic use , RNA, Viral/metabolism , SARS-CoV-2/physiology , Virus Replication
11.
BMJ Case Rep ; 14(5)2021 May 06.
Article in English | MEDLINE | ID: covidwho-1457886

ABSTRACT

Although prednisolone, granulocyte/monocyte apheresis, calcineurin inhibitor and anti-tumour necrosis factor (TNF) therapy are generally used, no treatment strategy for inflammatory bowel disease complicated with pyoderma gangrenosum (PG) has been established yet. Herein, we present the case of a 29-year-old man with ulcerative colitis (UC) complicated with primary sclerosing cholangitis. When UC relapsed and PG developed, prednisolone and granulocyte/monocyte apheresis were used; however, their therapeutic effects were deemed insufficient. After 2 weeks, adalimumab (ADA) induced remission; however, his UC and PG relapsed 20 weeks later. As a result of switching to infliximab, since a loss of response to ADA was deemed to have occurred, remission was reintroduced and subsequently maintained for 40 weeks. We conclude that anti-TNF-α antibodies might be selected as the first choice when PG and UC are refractory to treatment, and a switch to anti-TNFs should be considered when the effect is still insufficient.


Subject(s)
Biological Products , Cholangitis, Sclerosing , Colitis, Ulcerative , Pyoderma Gangrenosum , Adalimumab/therapeutic use , Adult , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/drug therapy , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Humans , Infliximab/therapeutic use , Male , Pyoderma Gangrenosum/complications , Pyoderma Gangrenosum/drug therapy , Tumor Necrosis Factor-alpha
12.
Rev Esp Enferm Dig ; 114(2): 118-119, 2022 02.
Article in English | MEDLINE | ID: covidwho-1406901

ABSTRACT

A new subcutaneous formulation of the infliximab biosimilar CT-P13 has recently been developed for the treatment of inflammatory bowel disease (IBD), providing response rates similar to intravenous treatment. The use of this new formulation was requested, in an effort to limit patient attendance at intravenous infusion centers and to maintain biological treatment during the COVID-19 pandemic. The objective of this observational, retrospective and descriptive study was to assess CT-P13 efficacy and safety after switching from intravenous to a subcutaneous formulation in patients with IBD receiving maintenance therapy. This article shows preliminary results after six months of follow-up.


Subject(s)
Biosimilar Pharmaceuticals , COVID-19 , Inflammatory Bowel Diseases , Biosimilar Pharmaceuticals/therapeutic use , Drug Substitution/methods , Gastrointestinal Agents/therapeutic use , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Pandemics , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
13.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
14.
J Crohns Colitis ; 15(4): 687-691, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1387845

ABSTRACT

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15-80 µg/L], C-reactive protein [CRP] [ >100mg/L for  >10 days, normal 0-5 mg/L], erythrocyte sedimentation rate [ESR] consistently  >100mm/h [normal 0-15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.


Subject(s)
COVID-19/diagnosis , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Infliximab/therapeutic use , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/complications , COVID-19/therapy , Child , Colitis, Ulcerative/complications , Female , Humans , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/therapy
16.
Eur J Pediatr ; 180(5): 1581-1591, 2021 May.
Article in English | MEDLINE | ID: covidwho-1384440

ABSTRACT

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.


Subject(s)
COVID-19/drug therapy , Infliximab/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , COVID-19/diagnosis , Child , Child, Preschool , Female , Humans , Infant , Male , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/diagnosis
17.
J Neuroimmunol ; 360: 577704, 2021 11 15.
Article in English | MEDLINE | ID: covidwho-1373149

ABSTRACT

COVID-19 infection can cause inflammatory reactions that could involve several organs. In the pediatric population, Multi-System Inflammatory Syndrome in Children (MIS-C) has been reported as one of the consequences of COVID-19. We report a unique pediatric COVID-19 patient with MIS-C, associated with paralysis of the extremities. MRI showed abnormal signal in the cervical spinal cord compatible with transverse myelitis. Methylprednisolone and IVIG were administered, without significant symptom improvement. As a next step, Infliximab was tried for her, and she responded remarkably well to this treatment. Infliximab may be considered as a treatment option in COVID-19 patients with transverse myelitis.


Subject(s)
COVID-19/complications , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/etiology , Systemic Inflammatory Response Syndrome/diagnostic imaging , Systemic Inflammatory Response Syndrome/etiology , Antirheumatic Agents/therapeutic use , COVID-19/diagnostic imaging , COVID-19/drug therapy , COVID-19/etiology , Child , Female , Humans , Infliximab/therapeutic use , Myelitis, Transverse/drug therapy , Systemic Inflammatory Response Syndrome/drug therapy
19.
J Crohns Colitis ; 16(2): 190-198, 2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1319160

ABSTRACT

BACKGROUND AND AIMS: Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.


Subject(s)
Drug Monitoring , Inflammatory Bowel Diseases , Self-Testing , Adalimumab/therapeutic use , COVID-19 , Cross-Sectional Studies , Drug Monitoring/methods , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Pandemics , SARS-CoV-2 , United Kingdom
20.
Gut ; 70(10): 1884-1893, 2021 10.
Article in English | MEDLINE | ID: covidwho-1203979

ABSTRACT

OBJECTIVE: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. DESIGN: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4ß7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. CONCLUSION: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Gastrointestinal Agents/adverse effects , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Serologic Tests
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