tofacitinib

Anti-MDA5-positive DM was diagnosed, and she was treated with triple therapy combined with tofacitinib because poor prognostic factors existed...Subsequent antibiotic therapy resolved both the cutaneous and pulmonary lesions. This case highlights the importance of considering bacteremia and performing blood cultures when DM-related skin ulcers resist conventional treatments, even without fever during immunosuppressive therapy.

Regardless of baseline BMI category, efficacy was greater with tofacitinib versus placebo in patients with AS, and no treatment effect differences between categories were observed, with exceptions for BMI ≥ 30 kg/m2 (more active/treatment-refractory disease and a smaller sample size). Overall, tofacitinib safety was generally comparable across categories; however, AE/SAE rates with tofacitinib were higher in the BMI < 25 kg/m2 category (which had more current smokers). This post hoc analysis demonstrates that tofacitinib can be considered as a treatment option for AS, regardless of baseline BMI category; however, interpretation was limited by small sample sizes and differences in sample sizes and baseline characteristics across categories.

In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

P=N/A, N=60, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P4, N=104, Recruiting, Charite University, Berlin, Germany | Not yet recruiting --> Recruiting | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Nov 2025 --> Mar 2025

P2, N=70, Recruiting, Stanford University | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=2, Terminated, Khashayar Esfahani | N=10 --> 2 | Trial completion date: Sep 2025 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Jan 2024; sponsor decision, due to low recruitment rate

P2, N=20, Not yet recruiting, M.D. Anderson Cancer Center

The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis)...Of a total 27 661 drug exposures, drug initiations consisted of 20 586 TNFi exposures (74%), 2570 JAKi exposures (9%), 2255 abatacept exposures (8%), 1182 rituximab exposures (4%), and 1068 IL-6i exposures (4%)...Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.

Furthermore, significantly lower tumor necrosis factor-α (TNFα), IL-6, and IL-1β levels (P < 0.05) were detected by enzyme-linked immunosorbent assay (ELISA) in homogenates of the joints treated with MDTs than in untreated arthritic joints. In conclusion, this study proposed effective MDTs that could deliver tofacitinib directly to inflamed joints possibly by targeting the macrophages circulating in the proximity of the site of inflammation.

He was administered alemtuzumab twice (at the time of initial treatment and relapse) and cyclophosphamide, vincristine, and hydrocortisone chemotherapy. Furthermore, novel therapeutic drugs (venetoclax and tofacitinib) were administered based on previous case reports...Consideration should be given to suspending treatment, adjusting the administration interval, or administering G-CSF if necessary. The treatment interval can be appropriately adjusted, making it a valuable treatment option for refractory T-PLL.

Of these, 29% did not have features consistent with anti-MDA5 disease. However, when present, MDA5 disease is severe with a high mortality.

P1, N=12, Not yet recruiting, Beijing Tiantan Hospital

P=N/A, N=24, Enrolling by invitation, Tongji Hospital

P4, N=308, Not yet recruiting, University Hospital, Toulouse

P=N/A, N=10, Not yet recruiting, Peking University Hospital of Stomatology; Peking University Hospital of Stomatology

In concordance with studies of background risk, AEs were more common in patients with CV risk enrichment, particularly those aged ≥ 65 years. Tofacitinib effectiveness/persistence were generally similar regardless of CV risk enrichment. These findings support individualised treatment benefit-risk assessment, including CV assessment/management, to optimise RA outcomes.

Our findings suggest that tofacitinib may reduce the risk of all-cause mortality in patients with anti-MDA5 antibody-positive DM-ILD without an increased risk of additional infections. PROSPERO: CRD42023445427; https://www.crd.york.ac.uk/prospero/.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P3, N=400, Not yet recruiting, Duke University

Furthermore, the elevated production of inflammatory cytokines observed in 3CK-treated hiPSC-COs was attenuated by treatment with tofacitinib. Our UC model will be an essential tool to understand its pathologic mechanisms and identify effective therapeutic approaches.

MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

P=N/A, N=116, Completed, Pfizer | Recruiting --> Completed | N=500 --> 116

P=N/A, N=20000, Active, not recruiting, Pfizer | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

She was treated with rituximab along with oral glucocorticoid and other supportive treatment to which she didn't respond adequately. So, we added tofacitinib as adjuvant therapy in our patient. Post-six months of commencement of adjuvant tofacitinib, patient experienced remarkable improvement in cutaneous features as well as in pulmonary fibrosis.

P4, N=75, Not yet recruiting, Post Graduate Institute of Medical Education and Research, Chandigarh

We demonstrated that JAKi prevent GM-CSF-induced CEACAM1 expression in neutrophils, and JAKi-induced inhibition depends on their selectivity against JAK isoforms. These findings suggest that JAKi can modulate the expression of CEACAM1 in cytokine-activated neutrophils, thereby limiting their activation.

P=N/A, N=18, Terminated, Pfizer | N=60 --> 18 | Trial completion date: Oct 2024 --> Apr 2024 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Apr 2024; Study was terminated due to difficulty in enrolling targeted number of participants. There were no safety and/or efficacy concerns in the decision to stop enrollment.

P=N/A, N=150, Recruiting, Pfizer | N=280 --> 150

To our knowledge, this is the first report of MDA5-DM complicated by breast cancer, as well as the first case of JAK inhibitor use for MDA5-DM with cancer. For curative treatment of MD5-DM with RP-ILD, if comorbid cancers are found, collaboration with oncologists to balance the efficacy and adverse events of MDA5-DM with RP-ILD therapy is essential in determining the appropriate type and timing of treatment, which could lead to a favorable outcome.

P=N/A, N=1442, Completed, Aetion, Inc. | Active, not recruiting --> Completed | N=3000 --> 1442

P3, N=400, Recruiting, University of Nebraska | Trial primary completion date: Mar 2026 --> Mar 2027

For rapidly progressive or interleukin-6 abnormally elevated steroid-refractory IRM, alemtuzumab or tocilizumab/tofacitinib are the preferred therapeutic agents, respectively. For steroid-refractory IRM comorbid with myositis or comorbid with myasthenia gravis, abatacept + ruxolitinib/mycophenolate mofetil (MMF)/intravenous immunoglobulin (IVIG), or MMF + pyridostigmine/IVIG are the preferred therapeutic agents, respectively. The pathogenesis of steroid-refractory IRM and the treatment regimen remain unclear. A large number of studies need to be conducted to validate or update our proposed treatment approach.

Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase-containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.

Subsequent development led to the creation of nine potent molecules, with derivatives 43 and 46 showing exceptional affinity upon evaluation through molecular dynamics simulation and MM/GBSA calculations over 300 nanoseconds, comparable to tofacitinib, an approved RA drug. However, compounds L21 and L46 demonstrated stable performance, suggesting their effectiveness in treating rheumatoid arthritis and other autoimmune conditions associated with JAK3 inhibition.

P=N/A, N=150, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

T-C@HP also alleviates colitis by regulating the colonic inflammatory microenvironment through multiple processes, including the modulation of apoptosis, macrophage polarization, tight junction, mucus layer, and intestinal flora. Complemented by satisfactory anti-inflammatory and biosafety results, this nanoplatform represents a promising, effective, and safe treatment option for colitis patients.

Tofacitinib and filgotinib are approved for treating ulcerative colitis (UC), while upadacitinib is approved for UC and Crohn's disease. Ozanimod and etrasimod are S1PRMs approved for the treatment of UC, but they can cause side effects such as bradycardia, conduction disorder, and macular edema. Overall, JAK inhibitors and S1PRMs offer significant benefits in managing IBD, although their potential side effects require careful monitoring.

In this study, novel pyrimidine compounds, BY4003 and BY4008, were synthesized to target the JAK3/STAT3 signaling pathway, and their therapeutic efficacy and mechanisms of action were evaluated and compared with Tofacitinib in U251, A172, LN428 and patient-derived glioblastoma cells...Results showed decreased expression of STAT3-associated proteins, including p-STAT3, CyclinD1, and Bcl-2, and increased expression of Bax, a pro-apoptotic protein, as well as significant down-regulation of STAT3 and STAT3-related genes. These findings suggested that BY4003 and BY4008 could inhibit GBM growth by suppressing the JAK3/STAT3 signaling pathway, providing valuable insights into the therapeutic development of GBM.

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.

P2, N=47, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

P1/2, N=13, Completed, Children's Hospital Medical Center, Cincinnati | Trial completion date: Dec 2022 --> Dec 2023