leflunomide

P=N/A, N=15, Active, not recruiting, University Hospital, Basel, Switzerland | Recruiting --> Active, not recruiting

Emerging biologics have significantly advanced the management of PsA, offering greater efficacy and safety compared to conventional DMARDs. IL-17 and IL-23 inhibitors, along with newer agents like bimekizumab, present promising treatment options for patients with inadequate responses to TNF inhibitors. Personalized treatment strategies, based on disease phenotype and individual patient needs, are essential for optimizing outcomes in PsA management. Further research into long-term efficacy and safety is required to refine treatment protocols and improve patient outcomes.

These data support a significant role for a type II IFN-associated immune response in SjD pathogenesis, which is targeted by LEF/HCQ. Proteins associated with type II IFN-driven immune responses hold potential to monitor disease activity and predict treatment response.

P1, N=20, Not yet recruiting, The First Affiliated Hospital of Xinxiang Medical University; The First Affiliated Hospital of Xinxiang Medical University

Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies-including RCI, rituximab, JAKi or investigational regimens-are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm.

The recent evolution in understanding the immunologic pathogenesis of sarcoidosis has led to the introduction of advanced treatment modalities for refractory cases resistant to steroids, methotrexate, and leflunomide, which are often used as first-line treatments. This refractory course was attributed to the emergence of infliximab-neutralizing antibodies, which rendered infliximab ineffective. This case raises awareness about a preventable progression of disease that may otherwise have a fatal outcome, mandating strict follow-up for the emergence of neutralizing antibodies and the need for concomitant low-dose methotrexate, prednisone, and/or azathioprine to prevent such life-threatening sequelae.

P2, N=1, Terminated, Tata Memorial Centre | Practice changes, including leflunomide use for CMV, have led to a lack of musculoskeletal GVHD cases. Only one patient enrolled in the trial will continue treatment as per standard care.

P2, N=80, Not yet recruiting, NYU Langone Health

P3, N=400, Recruiting, University of Nebraska | Trial completion date: Mar 2028 --> Mar 2029 | Trial primary completion date: Mar 2027 --> Mar 2028

To address these challenges, we developed GE11 peptide-modified polyphenol-iron chelate nanoparticles for co-delivery the long carbon chain-modified gemcitabine and the DHODH inhibitor leflunomide, with peptide modification enabling nanoparticles to target PDAC cells with high expression of epidermal growth factor receptor. In an in situ pancreatic cancer mouse model, this strategy exhibited superior anti-tumor efficacy compared to the standard AG chemotherapy regimen (nab-paclitaxel and gemcitabine), even at a 6.3-fold lower gemcitabine concentration. These findings underscore the potential of this approach as a highly effective therapeutic strategy for PDAC treatment.

Shifting mitochondrial dynamics toward fusion by targeting the MARCH5-MFN2 axis impairs ETC and OXPHOS, thereby sensitizing MM cells to venetoclax. These findings provide preclinical evidence for the potential therapeutic use of MFN2 inducers to enhance venetoclax responsiveness of MM patients.

P1/2, N=26, Recruiting, West Virginia University | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Aug 2025