adalimumab (9MW0113 / UBP 1211 / UBP1211)

Response to correspondence on 'Upadacitinib vs adalimumab in patients with rheumatoid arthritis and a prior inadequate response or intolerance to a tumour necrosis factor inhibitor: 12-week results from the randomised, double-blind, SELECT-SWITCH study' by Mysler et al.

Fleischmann Roy R, Nagy Orsolya O, Ren Jingchen J, Mysler Eduardo E

Small Bowel Adenocarcinoma Arising in Long-Standing Stricturing Crohn's Disease: Diagnostic Challenges and Therapeutic Dilemmas.

Mechhor Salma S, Cherkaoui Manal M, El Bacha Hicham H, Cherkaoui Malki Oumeima O et al.

Small bowel adenocarcinoma (SBA) is a rare but severe complication of long-standing Crohn's disease (CD), particularly in patients with stricturing phenotypes. Its diagnosis is often delayed due to overlapping clinical and radiological features with inflammatory disease. We report the case of a 52-year-old man with an 18-year history of stricturing and fistulizing ileal CD, previously treated with azathioprine and adalimumab. Despite clinical remission, magnetic resonance enterography performed during therapeutic reassessment revealed complex stricturing disease with fistulizing features. Surgical resection was undertaken. Histopathological examination revealed mucinous adenocarcinoma with a signet-ring cell component exceeding 30%, staged as pT2N0 after complete (R0) resection. Postoperative management included close radiological surveillance without adjuvant chemotherapy. Given the recent cancer diagnosis, a temporary treatment-free strategy for CD was initially adopted, with monitoring of fecal calprotectin levels. Endoscopic recurrence led to the introduction of ustekinumab. At 12-month follow-up, the patient remains clinically stable with no evidence of oncological recurrence. This case highlights the diagnostic challenge of SBA in CD, particularly in clinically quiescent patients. It underscores the absence of validated screening strategies and emphasizes the importance of multidisciplinary decision-making in balancing oncologic safety and inflammatory disease control.

Combination of small-molecule additives enhances recombinant protein expression in CHO cells via NF-κB pathway.

Zhang Xi X, Liu Rui R, Du Qiujie Q, Han Xuelian X et al.

Chinese hamster ovary (CHO) cells are a key platform for the production of recombinant therapeutic proteins. Supplementing serum-free medium (SFM) with small-molecule additives is an effective strategy for enhancing recombinant protein production. This study screened three small-molecule additives (baicalein, procyanidin and soy isoflavone) from eight candidates for their positive effects on recombinant protein expression. The optimal concentrations of these three additives were determined using the Design of Experiments (DOEs) approach. The results showed that the expression of secreted alkaline phosphatase (SEAP) and adalimumab increased by 3.14- and 3.43-fold at optimal concentrations of 172.7 μM baicalein, 800 μM procyanidin and 1.00 mM soy isoflavone. Flow cytometry analysis demonstrated that the three additives combination effectively arrested cell cycle at G0/G1 phase and inhibited apoptosis. Transcriptome sequencing revealed that differentially expressed genes (DEGs) exhibited significant enrichment in the NF-κB signaling pathway. Combination of baicalein, procyanidin and soy isoflavone significantly increased NF-κB phosphorylation and the expression of p21, cyclin D1, Bcl-2 and Bcl-xL, whereas it significantly decreased the expression of Bax and caspase-3. Our findings indicated that baicalein, procyanidin and soy isoflavone synergistically enhanced recombinant protein expression by activating the NF-κB signaling pathway, offering a potentially effective approach for improved recombinant protein production.

Is Routine Monitoring of TNF-α Inhibitor Levels and Antibodies in Pediatric IBD Justified in the Era of Personalized Medicine.

Pytrus Tomasz T, Szyller Hubert Paweł HP, Augustynowicz Gabriela G, Lasocka Maria M et al.

Inflammatory bowel disease (IBD) with an onset in childhood is characterized by a more extensive phenotype, a more aggressive clinical course, and a higher risk of long-term complications, including growth retardation, compared to adult-onset disease. While tumor necrosis factor-alpha (TNF-α) inhibitors are the cornerstone of therapy, achieving sustained remission in children is often hindered by unique pharmacokinetic challenges, such as accelerated drug clearance and a higher propensity for immunogenicity. This review explores the evolving role of therapeutic drug monitoring (TDM), specifically the paradigm shift from reactive to proactive strategies. While proactive TDM remains a subject of debate in adult IBD, emerging pediatric data strongly support its routine use to optimize treatment durability and prevent secondary loss of response. Evidence-based target trough concentrations for pediatric patients are critical for achieving mucosal healing: 8-13 µg/mL at week 6 and >5-7 µg/mL during maintenance for infliximab, and >13-14 µg/mL post-induction for adalimumab. Beyond clinical outcomes, this review emphasizes the economic viability of proactive TDM, which has been shown to reduce total healthcare expenditures by 18-30% by minimizing hospitalizations and avoiding premature treatment switches. By integrating pharmacological data with clinical pathways, proactive TDM serves as an essential tool for personalized medicine, ensuring safer and more cost-effective management of pediatric IBD.