Nathan Constantine-Cooke

Nathan Constantine-Cooke

Affiliations: MRC Human Genetics Unit & Centre for Genomic and Experimental Medicine



I am a Precision Medicine PhD student specialising in modelling biomarker trajectories and disease outcomes for inflammatory bowel disease. I am in the Vallejos group and collaborate closely with clinical colleagues in the Lees group.

My research interests include survival analysis, electronic health records, Bayesian statistics, and machine learning.

I am also an R package developer. My packages can be found on GitHub.

In my personal life, I enjoy swimming, the gym, playing bass guitar, and all things technology.

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News

Aug 17, 2022 Latent Crohn’s Disease Subgroups are Identified by Longitudinal Faecal Calprotectin Profiles is available on medRxiv!
Mar 23, 2022 gameR has been released on CRAN!
Feb 19, 2022 This website has gone live!
Nov 5, 2021 datefixR has been released on CRAN!

Selected publications

  1. TAG
    Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis
    Laura A. Lucaciu,  Nathan Constantine-Cooke, Nikolas Plevris, Spyros Siakavellas, Lauranne A.A.P. Derikx, Gareth-Rhys Jones, and Charles W. Lees
    Therapeutic Advances in Gastroenterology 2021

    Background and aims: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients. Methods: We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8–14 weeks) and maintenance (16–26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models. Results: Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41–60%) and 37% (26–45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31–50%) and 29% (23–36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%). Conclusion: Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials.

    @article{doi:10.1177/17562848211064004,
      abbr = {TAG},
      bibtex_show = {true},
      selected = {true},
      pdf = tag2021.pdf,
      author = {Lucaciu, Laura A. and Constantine-Cooke, Nathan and Plevris, Nikolas and Siakavellas, Spyros and Derikx, Lauranne A.A.P. and Jones, Gareth-Rhys and Lees, Charles W.},
      title = {Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis},
      journal = {Therapeutic Advances in Gastroenterology},
      volume = {14},
      number = {},
      pages = {17562848211064004},
      year = {2021},
      doi = {10.1177/17562848211064004},
      note = {PMID: 34987608},
      url = {https://doi.org/10.1177/17562848211064004},
      eprint = {https://doi.org/10.1177/17562848211064004}
    }
  2. medRxiv
    Latent Crohn’s Disease Subgroups are Identified by Longitudinal Faecal Calprotectin Profiles
    Nathan Samuel Constantine-Cooke, Karla Monterrubio Gomez, Nikolas Plevris, Lauranne A.A.P Derikx, Beatriz Gros, Gareth-Rhys Jones, Riccardo MarioniCharlie W. Lees, and Catalina Vallejos
    Aug 2022

    Background High faecal calprotectin is associated with poor outcomes in Crohn’s disease. Monitoring of faecal calprotectin trajectories could characterise disease progression before severe complications occur. Aims We undertook an unbiased assessment of a retrospective incident Crohn’s disease cohort to assess for inter-individual variability in faecal calprotectin levels over time. We aimed to explore whether latent classes of such profiles are associated with a composite endpoint consisting of surgery, hospitalisation, or Montreal behaviour progression and other clinical information. Methods Latent class mixed models were used to model faecal calprotectin trajectories within five years of diagnosis. Akaike information criterion, Bayesian information criterion, alluvial plots, and class-specific trajectories were used to decide the optimal number of classes. Log-rank tests of Kaplan-Meier estimators were used to test for associations between class membership and outcomes. Results Our study cohort comprised 365 subjects and 2856 faecal calprotectin measurements (median 7 per subject). Four latent classes were found and broadly described as a class with consistently high faecal calprotectin and three classes characterised by downward trends for calprotectin. Class membership was significantly associated with the composite endpoint, and separately, hospitalisation and Montreal disease progression, but not surgery. Early biologic therapy was strongly associated with class membership. Conclusions Our analysis provides a novel stratification approach for Crohn’s disease patients based on faecal calprotectin trajectories. Characterising this heterogeneity helps to better understand different patterns of disease progression and to identify those with a higher risk of worse outcomes. Ultimately, this information will assist the design of more targeted interventions.

    @article{ConstantineCooke2022,
      abbr = {medRxiv},
      bibtex_show = {true},
      pdf = lcmm-preprint.pdf,
      selected = {true},
      author = {Constantine-Cooke, Nathan Samuel and Gomez, Karla Monterrubio and Plevris, Nikolas and Derikx, Lauranne A.A.P and Gros, Beatriz and Jones, Gareth-Rhys and Marioni, Riccardo and Lees, Charlie W. and Vallejos, Catalina},
      title = {Latent Crohn{\textquotesingle}s Disease Subgroups are Identified by Longitudinal Faecal Calprotectin Profiles},
      year = {2022},
      month = aug,
      doi = {10.1101/2022.08.16.22278320},
      publisher = {Cold Spring Harbor Laboratory},
      url = {https://doi.org/10.1101/2022.08.16.22278320}
    }