Most TNFi could be more effective than JAKi and IL-17i. The safety of the therapies is generally good. However, the efficacy and safety of TNFi/IL-17i/JAKi remains to be further analyzed in studies with larger sample size and longer follow-up times.

Patients whose only risk factor is TNFi may in future follow vaccine recommendations for the general population. The South-Eastern Norway Regional Health Authority, The Coalition for Epidemic Preparedness Innovations (CEPI), Diakonhjemmet Hospital, Akershus University Hospital, Oslo University Hospital, University of Oslo, The Norwegian Research Council.

In conclusion, our data demonstrate that sterile pyramidal neuronal death is sufficient to cause epilepsy in the absence of other pathological processes. The CCL17-DTR mouse line may thus be a valuable model for further mechanistic studies on epilepsy and assessment of antiseizure medication.

The serological markers tested here have limited utility in predicting response to anti-TNF treatment. Further studies with larger sample sizes are needed to confirm the utility of ASCA IgG and pANCA.

Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR-2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

In conclusion, VDR rs2228570 and rs7975232 polymorphic variants were found to be related to vitamin D3 levels. Moreover, the genotyping of rs7975232 was also useful in evaluating disease onset and disease activity after 6 months of therapy with TNF inhibitors in RA patients.

While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

Monitoring serum humoral factors may offer valuable insights into the likelihood of therapeutic success of TNFi in patients with RA. IL-6 rebound at 14 weeks might serve as an early indicator of non-responsiveness to TNFi. These findings highlight the potential of personalized treatment strategies for RA based on serum humoral factor profiling. Larger prospective studies are needed to validate these results and elucidate the underlying mechanisms.

These results were slightly better than those of thalidomide. The obtained results revealed that Compound 12 had better immunomodulatory properties than thalidomide, with stronger effects on TNF-α, NF-κB P65, VEGF and caspase-8. This work indicates that compounds 7d and 12 have interesting biological properties that should be further evaluated and modified in order to develop clinically useful thalidomide analogs.

We recently reported that increased expression of ST3GAL1 was associated with inferior PFS in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed MM patients treated with bortezomib, thalidomide, and dexamethasone (VTd) +/- Dara as induction and consolidation within the CASSIOPEIA study. Conclusions : Within part 2 of CASSIOPEIA, increased expression of ST3GAL1 is significantly associated with inferior PFS and predicts lack of sustained MRD and disease progression in patients MRD negative (10-5) prior to the onset of maintenance therapy or observation. Our preliminary data suggest that desialylation strategies, currently in clinical development, could help achieve deep and durable remissions in MM patients receiving current Dara based quadruplet treatment approaches.

We found that milk concentrations of Tumor Necrosis Factor (TNF) and TNF-dependent chemokines (MIP-1β and IP-10) are low in women with inflammatory bowel disease who are receiving anti-TNF monoclonal antibody (TNFmAb), compared to those without concurrent anti TNF therapy. While maternal use of TNFmAb during breastfeeding is considered inconsequential to infant health due to their low levels of milk excretion, it affects profiles of endogenous cytokines in milk. Our findings provide a rationale to investigate human implications of the animal data in the literature that suggest enhancement of neurocognitive development of the offspring fed with milk deficient in TNF-dependent chemokines.

In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification.

Analyze whether the presence of the HLA-DQA1⋆05 allele is associated with the development of immunogenicity and to evaluate the disease response to anti-TNF drugs (infliximab (IFX) and adalimumab (ADA)), according to the presence of this allele. The risk of withdrawal, intensification, as well as antibody development, was higher in patients carrying the allele and on treatment with IFX or ADA. In our study, we demonstrated that there is an increased risk of immunogenicity in patients carrying the HLA-DQA1⋆05 genotype, which would support the idea of screening for this genetic variant before starting anti-TNF therapy, as its prevalence is high in the general population and increases the risk of treatment discontinuation due to loss of response.

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders. We report kinetic profiling and parameters of CK1α degradation, ternary complex, antiproliferative effects, in vitro ADME data, and in vivo pharmacokinetic studies with demonstrated oral bioavailability.

Notably, only the presence of anemia indicated a significant interaction (p for interaction=0.010); the HRs for drug discontinuation were 0.41 (95% CI 0.30~0.55) and 0.70 (95% CI 0.53~0.92) in the anemic and non-anemic groups, respectively. In the anemic subgroup, biologics were discontinued because of a lack of efficacy in 35.0% of TNFi initiators and 7.4% of TCZ initiators.Conclusion The drug discontinuation rate in biologic-naïve patients with RA was significantly lower for TCZ than for TNFi, particularly in those with anemia.

P=N/A, N=83, Recruiting, Hospital General de Mexico | Trial completion date: Mar 2024 --> Oct 2024

When patients with a recurrence of AML have a history of consuming or contacting aquatic products, clinicians should be vigilant about Aeromonas veronii infection. The presence of Aeromonas veronii in peripheral blood must alert clinicians to the possibility of severe sepsis and septic shock. Early diagnosis and prompt treatment are crucial to reducing patient mortality.

In the whole group H, significantly more patients obtained Clinical Disease Activity Index remission by tumor necrosis factor inhibitors (7/9, 77.8%) than by interleukin-6 inhibitors (1/6 (16.7%); p = 0.04). In patients with rheumatoid arthritis, interleukin-6 inhibitors may be more beneficial for patients with low femoral bone mineral density, whereas tumor necrosis factor inhibitors may be advantageous for those with preserved bone mineral density.

This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

We identified seven transcription factor candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF treatment. Correlation analysis between the expression of these transcription factors and IL10 suggests a role for MAF, PRDM1, and/or EOMES in regulating IL10 expression in CD4+ T cells upon anti-TNF treatment.

Our study reveals an association of TNF promoter hypomethylation with mucosal inflammation, suggesting that IBD patients may be particularly sensitive to inflammatory environmental insults affecting DNA methylation. Together, our analyses indicate that TNF promoter methylation analysis may aid in the characterization of IBD status and evaluation of anti-TNF therapy response.

P4, N=138, Recruiting, Xinhua Hospital, Shanghai Jiaotong University School of Medicine; Xinhua Hospital, Shanghai Jiaotong University School of Medicine

P4, N=400, Not yet recruiting, Xi'an Jiaotong University Second Affiliated Hospital; Xi'an Jiaotong University Second Affiliated Hospital

The ROC-SpA (Rotation Or Change of biotherapy after first anti-TNF treatment failure in axSpA patients) study is a prospective, randomised, multicentre, superiority open-label phase IV trial comparing an anti-IL-17 strategy (secukinumab or ixekizumab) to a second TNF blocker in a 1:1 ratio. It could also impact the international recommendation to manage patients with axSpA. NCT03445845 and EudraCT2017-004700-22.

Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines.

P2, N=48, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

We found a significant association between alleles at genes in the human HLA locus and the formation of adalimumab immunogenicity and low adalimumab drug-serum concentrations in large clinical studies of CD and UC patients. This work extends previous results in Crohn's disease to ulcerative colitis and directly shows a genetic association in patients with low drug concentrations. This work builds on existing literature to suggest genetic screening as a useful tool for clinicians concerned with patient anti-TNF immunogenicity.

The dog was treated with amputation of the penis, scrotal urethrostomy, and five adjuvant doses of doxorubicin along with thalidomide. Penile hemangiosarcoma seems to share the same aggressive behavior with other hemangiosarcomas seen in other anatomical locations. Therefore, surgery and chemotherapy may improve survival time in dogs with penile hemangiosarcoma as well.

By combining multiple ML algorithms, we developed a novel prognostic model with excellent performance in PAAD cohorts. ML also proved to be powerful for identifying biomarkers and potential targets for improved PAAD patient stratification and immunotherapy.

Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA.

Compared to healthy controls, psoriasis patients demonstrated shifts of the three B cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.

P2, N=11, Active, not recruiting, Inmune Bio, Inc. | Trial completion date: Sep 2024 --> Dec 2024

P2, N=201, Recruiting, Inmune Bio, Inc. | Trial completion date: Dec 2024 --> Apr 2025 | Trial primary completion date: Dec 2024 --> Mar 2025

Recognizing the parallels with oncogenic mutations, we emphasize the potential of targeted molecular inhibitors in the treatment of vascular malformations by repurposing anticancer drugs. This review delves into the recent development and future use of such agents for the management of slow- and fast-flow vascular malformations, including in more specific situations, such as prenatal treatment and the management of associated coagulopathies.

The patient received mesalazine, azathioprine, and corticotherapy, with no control of the inflammatory process. Faced with refractoriness to drug treatment and side effects of corticosteroids with an increased risk of severe infection due to cirrhosis, we opted to use infliximab for the treatment of UC...AIH is a rare cause of elevated transaminase levels in patients with UC. The best treatment to control the 2 conditions should be evaluated with vigilance for the side effects of medications, mainly infections, especially in patients with cirrhosis.

P2, N=48, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

This study proposes a novel regulatory mechanism of GCs and of TNFi mediated by LAG-3 upregulation in synovial monocytes and PBMCs. LAG-3 modulation may be a promising target for development of novel therapies for inflammatory arthritis.

In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Lenalidomide, a thalidomide derivative, is prescribed as maintenance therapy in multiple myeloma (MM). Consequently, B-cell lineage specifying transcription factors including Pax5, Spi1 and EBF1 were downregulated even after 7 days of thalidomide withdrawal. Our study thus provides a molecular mechanism of thalidomide-induced B-ALL whereby thalidomide alters the chromatin occupancy of IKZF1 at key B-cell lineage transcription factors leading to a persistent block in B-cell differentiation.

We performed a literature search and found that certain genes (IL23R, TNF, FBXL19, CTLA4, SLC12A8, TAP1) are strongly associated with the occurrence of PP in pediatric and adult patients during therapy with TNFi. The identification of the specific SNPs involved in the appearance of PP and other PAEs in patients treated with TNFi for various diseases and in different populations may later favor the recognition of those patients at a high risk of developing such adverse effects and could guide personalized therapeutic strategies in future years.

P=N/A, N=40, Recruiting, Children's Hospital of Fudan University | Not yet recruiting --> Recruiting

Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig.