The objective of this study is to assess the efficacy of hydroxychloroquine (HCQ) when combined with Mesalamine in reducing clinical and histologic disease activity in patients who have active mild to severe Ulcerative Colitis (UC) and also to assess the immunological effects of hydroxychloroquine in this population. These outcomes will be evaluated both clinically and experimentally. In vitro, flow cytometry will be employed to measure the expression of CTLA-4 on activated CD4+CD25+CD127- Tregs from patients prior to treatment with HCQ, and then at the end of a 4 month follow up period. Suppression assays will be used to determine the functional capacity of the patient derived Tregs. Clinically, patients will be monitored for remission as defined by reduction in patient reported stool frequency and rectal bleeding (mayo sub-score 0 or 1) and endoscopically, by improvement in mucosal appearance (mayo sub-score 0 or 1), all objective measures in the mayo score.

This is a single arm study to evaluate the efficacy and immunological effect of administering Hydroxychloroquine to patients of non-European ancestry who have active mild to severe Ulcerative Colitis in spite of Mesalamine therapy. 10 Participants will be recruited in Icahn School of Medicine at Mount Sinai and 10 in Emory University (20 across all sites).

Participants 18 years and above who identify as an individual of non-European ancestry with a diagnosis of Ulcerative Colitis will be approached for the study. Participants will be recruited from Mount Sinai IBD center prior to their standard of care endoscopy. Participants who meet the study's inclusion criteria i.e. If they currently have active disease, they will be able to receive the research medication.

Participants will be administered 400mg hydroxychloroquine tablets orally for four months in addition to Mesalamine. Pre and post medication clinical, endoscopic and immunological assessments will be compared. Participants will also be followed up with bi-monthly phone calls. Participants will have a post medication colonoscopy at the end of the 4 month period.

There is a risk of retinopathy and cardiomyopathy associated with long term use of the study drug at doses greater than 6.5mg/kg for more than 5 years. Participants will be screened for existing eye and heart disease and monitored pre and post medication for any new adverse effects.

Inclusion Criteria:

• Clinical diagnosis of mild to severe active Ulcerative Colitis (confirmed by endoscopy at screening),
• Currently taking mesalamine,
• Be an individual of non-European ancestry.
• Adult 18 years and older

Exclusion Criteria

• Current use of biologics, steroids or other UC medications not including mesalamine.
• Presence of hepatic or renal insufficiency
• Pregnancy or lactation
• Known allergic reactions to components of the Hydroxychloroquine, Chloroquine or quinine products.
• Any pre-existing macular disease or cardiac disease.
• Treatment with another investigational drug or other intervention within 4 weeks.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Beginning 9 months and ending 36 months following article publication.

Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. To achieve aims in the approved proposal. Investigators should contact study team.

The gastroenterologist who will review pre- and post-intervention endoscopy and pathology reports will be masked to any and all information about the study participants including disease severity and medication.