P4, N=80, Not yet recruiting, The Third Affiliated Hospital, Sun Yat-sen University; The Third Affiliated Hospital, Sun Yat-sen University

Treatment with prednisolone and mycophenolate mofetil was initiated, resulting in subsequent clinical improvement. In conclusion, this case of anti-MDA5 positive CADM underscores the diverse range of clinical and radiological findings and the diagnostic challenges they pose. It highlights the importance of anti-MDA5 antibodies as a valuable diagnostic and prognostic tool, given their association with an elevated risk of developing interstitial lung disease (ILD), which may follow a rapidly progressive course and can be further complicated by pneumomediastinum.

P3, N=350, Recruiting, Oculis | Trial completion date: Dec 2025 --> Jun 2026 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2025 --> Jun 2026

P2, N=300, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Feb 2024 --> Apr 2025

P2/3, N=38, Completed, Columbia University | Unknown status --> Completed

P1, N=23, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=10 --> 23 | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

P4, N=240, Active, not recruiting, Mayo Clinic | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. Our findings indicate a prevalence of NUDT15 variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for NUDT15 variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.

P2/3, N=108, Not yet recruiting, Institute of Liver and Biliary Sciences, India

P4, N=350, Not yet recruiting, Mayo Clinic | Initiation date: Oct 2024 --> Jan 2025

P2, N=52, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

Molecular studies, including western blot analysis and immunocytochemistry, revealed that Isotelekin reduced the expression of iNOS (Inducible nitric oxide synthase), COX-2 (Cyclo-Oxygenase 2), and p-IkBα (Phospho I-kappa-B-alpha), and significantly inhibited the nuclear translocation of NF-κB/p65. Based on these results, Isotelekin at 10 µm in in vitro and at 30 mg kg-1 in in vivo demonstrated strong anti-inflammatory and immunosuppressive therapeutic potential.

P2, N=170, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting | N=52 --> 170

P1/2, N=24, Completed, National Institute of Allergy and Infectious Diseases (NIAID) | N=10 --> 24

P2, N=177, Active, not recruiting, Institut Paoli-Calmettes | Unknown status --> Active, not recruiting | Trial completion date: Dec 2018 --> Jul 2026 | Trial primary completion date: Dec 2018 --> Jul 2026

P2, N=200, Recruiting, AHS Cancer Control Alberta | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026

P2, N=101, Active, not recruiting, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Recruiting --> Active, not recruiting

The majority of Greek patients with IBD have a favorable pregnancy outcome. Active inflammation during gestation and a diagnosis of ulcerative colitis are negatively associated with pregnancy outcomes.

P=N/A, N=5, Active, not recruiting, Pfizer | N=100 --> 5 | Trial completion date: Feb 2026 --> Jan 2027 | Trial primary completion date: Feb 2026 --> Jan 2027

P1/2, N=0, Withdrawn, Selecta Biosciences, Inc. | Suspended --> Withdrawn

In selected patients with permanently unresectable colorectal liver metastases, liver transplantation plus chemotherapy with organ allocation priority significantly improved survival versus chemotherapy alone. These results support the validation of liver transplantation as a new standard option for patients with permanently unresectable liver-only metastases.

Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.

Prednisone was reinitiated at 1 mg/kg, and she was started on mycophenolate mofetil (MMF). Despite this, a rapid response to corticosteroids was observed including reversal of profound transfusion dependence, normalization of hemoglobin, and reversal of biochemical evidence of hepatic inflammation. A shared pathogenesis of autoimmune fibrosis in both the bone marrow and liver is speculative but suggested by the temporal association in this case.

In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients.

P4, N=204, Completed, Chinese PLA General Hospital | Recruiting --> Completed

P3, N=84, Completed, University Medical Center Groningen | Unknown status --> Completed

P2, N=30, Recruiting, Chinese PLA General Hospital

P4, N=60, Active, not recruiting, Vanderbilt University Medical Center | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P4, N=350, Not yet recruiting, Mayo Clinic

P2, N=21, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting

P1, N=28, Completed, Yale University | Recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024 | Trial primary completion date: Jul 2024 --> Jan 2024

P4, N=20, Recruiting, University Hospital, Antwerp | Not yet recruiting --> Recruiting

P4, N=130, Completed, University Hospital, Strasbourg, France | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: Nov 2023 --> Aug 2024

P=N/A, N=57, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2025 --> Aug 2024

P1, N=45, Recruiting, Brexogen Inc. | N=27 --> 45 | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Apr 2024 --> Dec 2025

P=N/A, N=0, Withdrawn, Beth Israel Deaconess Medical Center | N=66 --> 0 | Not yet recruiting --> Withdrawn

P4, N=823, Completed, First Affiliated Hospital of Guangxi Medical University | Recruiting --> Completed | Trial completion date: May 2023 --> Oct 2023

P1, N=0, Withdrawn, Brexogen Inc. | N=18 --> 0 | Not yet recruiting --> Withdrawn

P2, N=52, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=40, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.

Incorporation of the 8-amino acid sequence SQVAVQKR into this enzyme created a putative phosphorylation site and resulted in elevated nucleosidase activity, which is a known consequence of gain-of-function mutations in NT5C2 and a common determinant of 6-mercaptopurine (6-MP) resistance. Furthermore, both the NT5C2ex6a and R238W variants induced collateral sensitivity to the inosine monophosphate dehydrogenase (IMPDH) inhibitor mizoribine. These results ascribe an important role for splicing perturbations in chemotherapy resistance in relapsed B-ALL and suggest that IMPDH inhibitors, including the commonly used immunosuppressive agent mycophenolate mofetil, could be a valuable therapeutic option for treating thiopurine-resistant leukemias.