Ultra-high dose of mesalamine to treat steroid-dependent ulcerative colitis
Bibliographic record
Abstract
To the Editor: To the best of our knowledge, the use of ultra-high doses of mesalamine to treat ulcerative colitis (UC) has not been previously reported. We are reporting a UC patient whose treatment with an ultra-high dose of mesalamine resulted in the ability to eliminate steroid-dependence. A 25 year old male presented in another city with bloody diarrhea, and was diagnosed with ulcerative pan-colitis. He was initially treated with a cortico-steroid and mesalamine (Salofalk, Mesalamine Delayed Release Tablets USP, Aptalis Pharma Canada Inc.) 4.0 g/day. Because of steroid dependency, azathioprin was added. After being steroid-dependent for 6 months on triple therapy (prednisone 20–30 mg/day, mesalamine 4 g/day, and azathioprine 150 mg/day), he was advised to start anti-TNF therapy. He declined, and sought another opinion. The second gastroenterologist switched him from Salofalk tablets to mesalamin (MezavantR, 1.2 g Delayed-and Extended-Release Tablets, Shire Canada Inc.). The patient assumed that the dosing regimen was the same, and took 4.8 g BID. Soon after the 5-ASA therapy was increased to the ultra-high dose of 9.6 g/day, he was able to taper and stop prednisone for the first time since his diagnosis, and remain in clinical remission. At that time he moved to Toronto, and was referred to us for ongoing management. When we first encountered the patient, he had been on the ultra-high dose of 5-ASA for 6 months. We did not observe any adverse effects of this ultra-high dose of mesalamine. He was tolerating the ultra-high dose of mesalamine very well, and his urinalysis, complete blood count, liver and kidney profiles were all within the normal range. Thiopurine metabolite levels were therapeutic. While some studies have shown that higher doses of delayed-release mesalamine produced greater mucosal healing and faster colitis improvement versus lower doses 1, other trials have not shown the same results for doses ranging from 1.6 to 4.8 g 2. It has been shown that standard high oral doses of 5-ASA (from 2.4 to 4.8 g/day) can be effective in reducing or eliminating steroids in up to 50% of patients with steroid-dependent UC 3. Studies have shown that the colonic mucosal concentrations of 5-ASA are significantly higher in patients receiving combined oral and topical formulations compared to oral therapy alone, and that there is an inverse relationship between mucosal concentrations of 5-ASA and colitis disease activity, as measured by histological or endoscopic evaluations 4. We believe that an ultra-high dose of mesalamine should result in higher colonic mucosal concentrations of 5-ASA, hence a greater chance of effective disease control. Since mesalamine has not been reported to have dose-related side effects 5, one might anticipate that other patients would be able to tolerate ultra-high doses of mesalamine. In conclusion, using higher than recommended doses of mesalamine may have an important role in achieving clinical remission in selected ulcerative colitis patients. Further clinical studies are needed to examine the potential benefits and risks of an ultra-high dose of mesalamine in UC patients. Nil. No conflict of interest for any of the authors. Conception and design: Fred Saibil, Soleiman B Kashkooli; acquisition of data, initial drafting: Soleiman B Kashkooli, Mehrdad Rouhani; preparation of the final transcript: Soleiman B Kashkooli; critical revision of the transcript and supervision: Fred Saibil. All authors read and approved the final version of the transcript.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.012 | 0.010 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".