Nathan Constantine-Cooke

Nathan Constantine-Cooke

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



I am a postdoctoral research associate in health data science with interested in modelling longitudinal biomarker trajectories and disease outcomes for inflammatory bowel disease. I am in the Lees group in the Centre for Genomic and Experimental Medicine and in the Vallejos group in the MRC Human Genetics Unit.

My research interests include longitudinal modelling, survival analysis, electronic health records, 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.

Avatar

News

Apr 6, 2023 Longitudinal Fecal Calprotectin Profiles Characterize Disease Course Heterogeneity in Crohn’s Disease is now available at Clinical Gastroenterology and Hepatology!
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 Dec 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},
      month = dec,
      year = {2021},
      doi = {10.1177/17562848211064004},
      note = {PMID: 34987608},
      altmetric = {119733825},
      url = {https://doi.org/10.1177/17562848211064004},
      eprint = {https://doi.org/10.1177/17562848211064004}
    }
  2. CGH
    Longitudinal Fecal Calprotectin Profiles Characterize Disease Course Heterogeneity in Crohn’s Disease
    Nathan Constantine-Cooke, Karla Monterrubio-Gómez, Nikolas Plevris, Lauranne A.A.P. Derikx, Beatriz Gros, Gareth-Rhys Jones, Riccardo E. Marioni, Charlie W. Lees, and Catalina A. Vallejos
    Clinical Gastroenterology and Hepatology Mar 2023

    Background and Aims The progressive nature of Crohn’s disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterize the heterogeneity of disease trajectories in Crohn’s disease by utilizing objective markers of inflammation. We aimed to better understand this heterogeneity by clustering Crohn’s disease patients with similar longitudinal fecal calprotectin profiles. Methods We performed a retrospective cohort study at the Edinburgh IBD Unit, a tertiary referral center, and used latent class mixed models to cluster Crohn’s disease subjects using fecal calprotectin observed within five years of diagnosis. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-squared, Fisher’s exact test, and ANOVA were used to test for associations with variables commonly assessed at diagnosis. Results Our study cohort comprised of 365 patients with newly diagnosed Crohn’s disease and 2856 fecal calprotectin measurements taken within five years of diagnosis (median 7 per subject). Four distinct clusters were identified by characteristic calprotectin profiles: a cluster with consistently high fecal calprotectin and three clusters characterized by different downward longitudinal trends. Cluster membership was significantly associated with smoking (p = 0.015), upper gastrointestinal involvement (p < 0.001), and early biologic therapy (p < 0.001). Conclusions Our analysis demonstrates a novel approach to characterizing the heterogeneity of Crohn’s disease by using fecal calprotectin. The group profiles do not simply reflect different treatment regimens and do not mirror classical disease progression endpoints.

    @article{Constantine_Cooke_2023,
      abbr = {CGH},
      bibtex_show = {true},
      selected = {true},
      pdf = {LCMM_CGH.pdf},
      doi = {10.1016/j.cgh.2023.03.026},
      issn = {1542-3565},
      url = {https://www.sciencedirect.com/science/article/pii/S1542356523002343},
      year = {2023},
      month = mar,
      altmetric = {144689897},
      publisher = {Elsevier {BV}},
      author = {Constantine-Cooke, Nathan and Monterrubio-G{\'{o}}mez, Karla and Plevris, Nikolas and Derikx, Lauranne A.A.P. and Gros, Beatriz and Jones, Gareth-Rhys and Marioni, Riccardo E. and Lees, Charlie W. and Vallejos, Catalina A.},
      title = {Longitudinal Fecal Calprotectin Profiles Characterize Disease Course Heterogeneity in Crohn's Disease},
      journal = {Clinical Gastroenterology and Hepatology},
      keywords = {Biomarker, Epidemiology, Monitoring}
    }