Lead Investigator: Andrea E. van der Meulen – de Jong, Leiden University Medical Center
Title of Proposal Research: Anemia and therapy with Janus Kinase Inhibitors in patients with ulcerative colitis
Vivli Data Request: 8686
Funding Source: None
Potential Conflicts of Interest: A.E. van der Meulen – de Jong received unrestricted research grants from Vedanta, Nestle, Norgine, Galapagos, and received speaker’s fees from Tramedico, Takeda, Galapagos, and Janssen Pharmaceuticals. None of these companies have an impact on the interpretation of the results.
R. Loveikyte has received speaker’s fees and served on the advisory board of Cablon Medical, and received travel expenses from Galapagos and Cablon Medical. None of these companies have an impact on the interpretation of the results.
Summary of the Proposed Research:
Ulcerative colitis (UC) is one of the two entities of inflammatory bowel disease (IBD). In the Netherlands, about 90,000 patients suffer from IBD. UC is characterized by inflammation of the large intestine. The inflammation causes sores, rectal bleeding, abdominal pain, reduced quality of life, and it is linked to a higher risk of colorectal cancer. There is no cure for UC; however, therapy with medications such as Janus Kinase Inhibitors (e.g., tofacitinib, filgotinib, upadacitinib) can treat the inflammation and reduce the risk of colorectal cancer. In recent years, many different medications have been shown effective in treating UC. Most of these medications are almost equally effective, but patients can experience primary and secondary loss of response and due to various mechanisms of action the medications are linked to different types of side effects.
Janus Kinase Inhibitors (JAKi) are one of the newest medications for UC. Due to the mechanism of action, JAKi might cause the following abnormalities in the blood: a reduction in the number of red blood cells that transport oxygen, cells that help blood clot, and cells that help fight infections. Previous studies have shown patients with UC suffering from a reduced number of red blood cells need to use healthcare services more frequently, have a lower quality of life, and have an increased risk of being admitted to a hospital. For this reason, international guidelines advise physicians to regularly screen and treat patients for these abnormalities.
We aim to evaluate how many patients are affected by these abnormalities during treatment with JAKi and whether different types of JAKi are more or less likely to cause these abnormalities in the blood. Due to the lack of literature, we will analyze existing data from clinical trials during therapy with a placebo, filgotinib, or tofacitinib. The results of this study will inform the need for future studies to investigate these abnormalities in greater detail and will eventually aid in formulating clinical guidelines for physicians regarding the appropriate management of patients who are about to start or are already undergoing treatment with JAKi.
Statistical Analysis Plan:
Descriptive data will be reported as mean values with Standard Deviation (+/- D) or median values with an interquartile range [IQR: Quartile 1 – Quartile 3] for continuous variables. Categorical variables will be presented as a number (n) of the total available data with corresponding percentages (%). Normality assessment will be performed by visually inspecting normal probability plots (Q-Q) and histograms. The prevalence of anemia, leukopenia, and thrombocytopenia at the three study time points will be reported as an absolute number (n) with corresponding percentages (%). Group comparisons will be analyzed using chi-square, Mann-Whitney U, unpaired or paired t-test, or the Kruskal-Wallis test. A two-tailed P-value < 0.05 will be considered statistically significant. The Benjamini-Hochberg procedure will be used to adjust for multiple testing with a 5% false discovery rate.
Complete case analysis will be performed in case of data “missing completely at random”. Multiple imputation may be used to handle missing data in case of data “missing at random”. Limitations of used methods will be discussed in the final manuscript.
The studies, which are listed on the Vivli platform, were chosen because they include patients of interest (i.e., patients with ulcerative colitis) undergoing relevant treatment regarding the research question (i.e., treatment with tofacitinib).
We would like to test the following hypotheses:
– There is no difference in the prevalence of anemia after eight weeks of treatment between patients in the tofacitinib or placebo groups
– There is no difference in the prevalence of newly developed anemia after eight weeks of treatment between patients in the tofacitinib or placebo groups
– There is no difference in the number of patients who recovered from anemia after eight weeks of treatment between patients in the tofacitinib or placebo groups
– There is no difference in the prevalence of anemia between female and male sex after eight weeks of treatment with tofacitinib
– There is no difference in the prevalence of anemia between patients in remission and those with active disease after 8 weeks of treatment with tofacitinib
We will compare summary-level data from the trials listed in this request and from the SELECTION trial (NCT: NCT02914522). We will test the following hypotheses:
– There is no difference in the prevalence of anemia after the induction phase between patients treated with tofacitinib or filgotinib
– There is no difference in the prevalence of newly developed anemia after the induction phase between patients treated with tofacitinib or filgotinib
– There is no difference in the number of patients who recovered from anemia after the induction phase between patients treated with tofacitinib or filgotinib
Requested Studies:
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
Data Contributor: Pfizer Inc.
Study ID: NCT01465763
Sponsor ID: A3921094
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis.
Data Contributor: Pfizer Inc.
Study ID: NCT01458951
Sponsor ID: A3921095
A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis
Data Contributor: Pfizer Inc.
Study ID: NCT01458574
Sponsor ID: A3921096
Public Disclosures:
Loveikyte, R., Voorneveld, P.W., Dijkstra, G. and van der Meulen-de Jong, A.E., 2024. P923 Haematological abnormalities during treatment with Janus kinase inhibitors in patients with Ulcerative Colitis: a post hoc analysis. Journal of Crohn’s and Colitis, 18(Supplement_1), pp.i1681-i1681. Doi: 10.1093/ecco-jcc/jjad212.1053