The randomized controlled trials (RCTs) of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy or combined with csDMARD in the treatment of active RA were searched in database of PubMed, Embase, Web of Science and Cochrane Library, up to December 2023. Combination therapy with csDMARD might be more suitable for the maintenance of long-term efficacy. However, in clinical practice, it is still necessary to select the appropriate therapeutic regimen based on the actual clinical situation.

P1, N=49, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

P2, N=121, Recruiting, Telios Pharma, Inc. | Trial primary completion date: Dec 2023 --> Jun 2025

Univariate and multivariate logistic regression analysis showed that the baseline log sTNFR II values (OR: 0.002; p = 0.034) were predictors of CR. Patients with RA can be stratified prior to JAKinib administration using serum sTNFR-I and sTNFR-II levels but not serum IL-6 axis cytokine levels (IL-6, sIL-6R, and sgp130).

P1, N=24, Recruiting, Fox Chase Cancer Center | Not yet recruiting --> Recruiting

P2, N=93, Completed, CSPC Ouyi Pharmaceutical Co., Ltd. | Recruiting --> Completed

P1, N=9, Active, not recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

In addition, WU derivatives effectively downregulated CXCR3 and T-bet in primary murine T cells. In summary, we have generated novel JAK inhibitors that could serve as alternatives to baricitinib or ruxolitinib.

P1, N=8, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=15 --> 8

P2, N=56, Recruiting, Stanford University | Trial completion date: May 2024 --> Nov 2024 | Trial primary completion date: May 2024 --> Nov 2024

P2, N=24, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.

P3, N=92, Recruiting, LEO Pharma | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

P2, N=10, Recruiting, Yale University | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Feb 2024 --> Dec 2024

P2, N=10, Active, not recruiting, William Damsky | Recruiting --> Active, not recruiting

Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment.

P2, N=25, Recruiting, University of Washington | Trial completion date: Nov 2024 --> Nov 2026 | Trial primary completion date: Nov 2024 --> Nov 2026

P1, N=26, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial completion date: Nov 2023 --> Nov 2025 | Trial primary completion date: May 2023 --> May 2025

P=N/A, N=200, Recruiting, Pfizer | Trial completion date: Jun 2024 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2026

P3, N=249, Recruiting, Sanofi | Not yet recruiting --> Recruiting

In this study, we delved into the underlying mechanisms of specific BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib, ZM-306416, and AT-9283) in human melanoma A375P cells. Consequently, the expression of the E2F target genes (CCNA2, CCNE1, POLA1, and TK-1) was markedly suppressed in nilotinib and AT9283-treated A375P cells. In summary, our findings suggest that BCR-ABL tyrosine kinase inhibitors may regulate the G1-to-S transition in human melanoma A375P cells by modulating the RB-E2F complex.

P1, N=49, Not yet recruiting, Washington University School of Medicine | Phase classification: P2 --> P1

P1, N=55, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting

P2, N=40, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

While tofacitinib has been proposed to be a therapeutic option for anti-MDA5-DM-ILD, other JAK inhibitors, including baricitinib, are a treatment option. Further investigation is warranted to optimize treatment of anti-MDA5-DM-ILD.

Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA.

P2, N=61, Active, not recruiting, Fred Hutchinson Cancer Center | N=99 --> 61

Our research has demonstrated that DLGAP5 is upregulated in LUAD and exhibits a strong correlation with unfavorable prognosis. Furthermore, DLGAP5 assumes a significant function in the regulation of tumor immunity and treatment outcome of immune checkpoint inhibitors. Of note, we found that DLGAP5 promotes cell proliferation of LUAD via upregulating PLK1. Targeting DLGAP5 by AT9283, our newly identified DLGAP5 inhibitor, suppresses LUAD growth. DLGAP5 may become a promising prognostic biomarker and therapeutic target for patients with LUAD.

P1, N=55, Recruiting, Washington University School of Medicine | Trial completion date: May 2024 --> Sep 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.

P1, N=48, Recruiting, Biora Therapeutics, Inc.

P2, N=35, Completed, LEO Pharma | Phase classification: P2a --> P2

P3, N=249, Not yet recruiting, Sanofi

These findings have been confirmed in clinical studies which have further demonstrated the safety and efficacy of JAK inhibition as a means to overcome resistance to currently available anti-MM therapies. Additional studies will provide further support for this promising new therapeutic approach for treating patients with MM.

P4, N=60, Recruiting, Chinese University of Hong Kong | Not yet recruiting --> Recruiting

P1/2, N=93, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

P1, N=60, Not yet recruiting, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

P=N/A, N=200, Recruiting, Pfizer | Trial completion date: May 2025 --> Jun 2024 | Trial primary completion date: May 2025 --> Jun 2024

P1, N=24, Not yet recruiting, Fox Chase Cancer Center

Besides, all compounds sufficiently interacted with surrounding amino acids in all crucial regions, including glycine, catalytic, and activation loops. Altogether, PD12 and PD19 identified here could potentially be developed as novel therapeutic inhibitors disrupting the JAK/STAT pathway.