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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Ruxolitinib is also a potent JAK1 and JAK2 inhibitor administered orally. It was approved by FDA against myelofibrosis in November 2011. It shows its effect by inhibiting clathrin-mediated endocytosis but a pharmacokinetic study showed that the unbound plasma concentration of the drug required to produce this effect is much more than the tolerated therapeutic dose. Thus, it is unlikely to reduce the viral infectivity at therapeutic dose on the contrary, it may inhibit JAK resulting in reduced inflammatory response. A clinical trials for determining the efficacy of Ruxolitinib are underway [10].
Emerging Oral Treatments: Oral JAK Inhibitors for Alopecia Areata
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Jared Marc John, Rodney Sinclair
The JAK inhibitor tofacitinib targets JAK3/JAK1 over JAK2 and TYK2. It is FDA approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Ruxolitinib is a JAK1/JAK2 inhibitor that is FDA approved for myelofibrosis, polycythaemia vera and graft-versus-host disease. Baricitinib is a JAK1/JAK2 inhibitor that is FDA approved for rheumatoid arthritis [4, 8, 12]. Other experimental JAK inhibitors are in various trial stages for dermatological conditions (Table 11A.1).
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most common side effects of ruxolitinib include GI symptoms (e.g., constipation, flatulence), hematological disorders (e.g., anemia, bruising, dyslipidemia, thrombocytopenia, hemorrhage, neutropenia), cardiovascular problems (e.g., hypertension), dizziness, headache, increased risk of infection, sepsis, and weight increase.
Recent progress of JAK inhibitors for hematological disorders
Published in Immunological Medicine, 2023
Many studies have investigated the clinical factors that determine the response to ruxolitinib, as summarized in Table 2. Analysis of the data from JUMP, a multicenter prospective phase 3b study, indicated that a lower DIPSS score, early treatment with ruxolitinib and a dose of ruxolitinib were critical for spleen response [19]. A study out of Italy reported that a higher DIPSS score, transfusion dependency, lower platelet counts, large spleen size and a lower ruxolitinib dose negatively impacted the spleen response [20]. Regarding the prediction of ruxolitinib’s effect on survival benefit, Palandri et al. reported that the durability of the spleen response was correlated with a favorable survival response [21]. Furthermore, Maffioli et al. established a scoring system named RR6 to predict survival after six months of treatment with ruxolitinib (response to ruxolitinib after six months), comprised of ruxolitinib dose, spleen response and transfusion requirement [22].
Updated recommendations on the use of ruxolitinib for the treatment of myelofibrosis
Published in Hematology, 2022
Timothy Devos, Dominik Selleslag, Nikki Granacher, Violaine Havelange, Fleur Samantha Benghiat
In patients with low- or intermediate-1-risk MF without splenomegaly but with a high disease burden, ruxolitinib may reduce disease-related inflammation and constitutional symptoms, and improve survival and quality of life. Mutation-based scoring systems and presence of HMR mutations could be used to identify patients at increased risk for aggressive clinical course [26,27]. Besides prognosis, the presence of a high disease burden may also be considered to guide treatment strategies for patients with low- or intermediate-1-risk MF, as suggested in a recently proposed treatment algorithm [27]. However, additional studies are needed to determine whether potential benefits of early ruxolitinib given alone or in combination with other drugs outweigh potential risks and to evaluate the impact of the mutational status and disease burden in this population.
Evaluating the use of JAK inhibitors in inflammatory connective tissue diseases in pediatric patients: an update
Published in Expert Review of Clinical Immunology, 2022
Jane Chuprin, Lindsay McCormack, Jillian M. Richmond, Mehdi Rashighi
There are a few case reports of JAKi use in young patients with lupus. One patient reportedly experienced benefits from a compassion trial of ruxolitinib for a severe form of familial chilblain lupus (FCL). FCL is an autosomal dominant disease diagnosed in early childhood and is characterized by cold-induced inflammatory lesions and an elevated type I IFN signature in the skin and blood that can lead to systemic complaints. The patient in this report was diagnosed with FCL at 6-months-old and was treated with hydroxychloroquine, methotrexate, and steroids without benefit. However, when treated with ruxolitinib at an initial dose of 5 mg twice a day (0.62 mg/kg/day), she demonstrated rapid clinical improvement after 1 week. After 12 months of well-tolerated ruxolitinib treatment, skin lesions almost completely resolved [52]. Similarly, in a family with five members with FCL, two members were treated with tofacitinib 5 mg/day for 17 days and demonstrated a decrease in Type I IFN markers and pain [53]. This is in line with other adult FCL patients that had significant improvement with baricitinib [54]. Another report details a young 9 year old female patient with SLE who experienced neurological symptoms that were refractory to standard therapy, but that improved with a trial of baricitinib and tapered glucocorticoids [55]. Lastly, there is one clinical trial investigating the expression of JAK3 in blood and renal tissue during active stages of disease in lupus patients ages 7–16 (NCT04293510). The results of this study may further support the use of targeted JAKi for pediatric lupus patients.