Ustekinumab is effective and safe in the treatment of Crohn’s disease refractory to anti-TNFα in an orthotopic liver transplant patient
Bibliographic record
Abstract
Dear Sir, Hepatobiliary disorders may be an extraintestinal manifestation of inflammatory bowel disease (IBD). The most common associated liver disease is primary sclerosing cholangitis (1–14%), followed by non-specific chronic hepatitis, chronic hepatitis C and non-alcoholic fatty liver.1 These conditions can progress towards end-stage liver disease and require orthotopic liver transplantation. We present the case of a 44-year-old male diagnosed in 1992 with Crohn’s disease (CD) with ileocecal involvement and an inflammatory pattern (A2L3B1 of the Montreal classification) refractory to corticosteroids, and which required ileocecal resection with ileocolic anastomosis. Subsequently, cryptogenic cirrhosis was diagnosed and liver transplantation was performed in 1998, with immune suppression in the form of tacrolimus. In 2001 the patient suffered from postoperative recurrence of IBD that was treated with prednisolone and 5-acetylsalicylic acid, with a good response. Since 2003 he had experienced multiple relapses, and anti-tumour necrosis factor α (TNFα) treatment with adalimumab was started in 2011. The patient responded favourably, though in 2012 the treatment was switched to infliximab due to a loss of response, and to certolizumab in 2013 for the same reason. In 2014 he was admitted due to a severe flare-up. Colonoscopy revealed left segmental colitis with ulcers and a simple endoscopic score for CD (SES-CD) of 7 points in the affected segment (Figure 1 After discarding infectious processes, treatment was started with intravenous corticosteroids and ustekinumab at a dose of 90 mg/week via the subcutaneous route for 1 month, followed by maintenance therapy with 45 mg/month via the subcutaneous route. The course proved favourable, and after 12 months of treatment the patient showed clinical remission, without corticosteroids, and endoscopy showed mucosal healing. There were no rejection problems or associated infectious processes. In patients with IBD before solid organ transplantation, the disease takes a more aggressive course, with greater resistance to medical treatment and a higher percentage of colectomies.2,3 The early introduction of 5-aminosalicylates after transplantation and the use of azathioprine appear to exert a protective effect.3 Regarding the use of anti-TNFα drugs, the scientific evidence is limited, but the literature reports clinical response rates of up to 87%, with mucosal healing in up to 42% of cases.4 Ustekinumab is a monoclonal antibody targeted to the p40 subunit of interleukin 12–23, resulting in inhibition of its mechanism of action. This drug has not been approved for use in CD, though there are preliminary clinical trials that suggest its usefulness in patients with CD refractory to anti-TNFα therapy.5 Our case is the first published report of a patient with CD and orthotopic liver transplantation refractory to anti-TNFα therapy in which ustekinumab proved effective and safe. No specific funding has been received for the present work. There is no conflict of interest to declare by the authors. All authors contributed equally.
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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".