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Axial Spondyloarthritis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
In December 2021, tofacitinib became the first Janus kinase (JAK) inhibitor that was approved by the Food and Drug Administration (FDA) for the treatment of AxSpA. Promising data has also emerged for filgotinib and upadacitinib in the treatment of this disease.28–30 The mechanism by which these drugs may impact activity in AxSpA remains somewhat nebulous. Despite this, these drugs have demonstrated efficacy in phase 2 and/or 3 trials in ankylosing spondylitis. As of this writing, it remains unclear where these agents may establish their role in treatment of this disease, particularly in light of emerging safety data related to these medications in patients with RA who have cardiovascular risk factors.31
Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Ruxolitinib (JakaviTM in the EU, JakafiTM in the US), developed by Novartis after licensing from Incyte, was the first JAK inhibitor to be approved (2011), and this was for the treatment of myelofibrosis. Other JAK/STAT inhibitors have since been developed, but these are mostly for inflammatory diseases. For example, tofacitinib (XeljanzisTM) is used to treat moderate to severe active psoriatic arthritis or rheumatoid arthritis in adults who have failed on methotrexate or related medications. Tofacitinib is sometimes given in combination with methotrexate or other arthritis medicines to treat psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and ulcerative colitis. Other analogues include filgotinib (GLPG0634), which is currently under development by Gilead/Galapagos. The pharmaceutical company Eli Lilly has developed baricitinib (OlumiantTM), which selectively and reversibly inhibits JAK1 and JAK2 and is used to treat rheumatoid arthritis in patients who have had an inadequate response to other anti-rheumatic agents. Finally, AbbVie has developed upadacitinib (RinvoqTM), which, like filgotinib, is a selective and reversible inhibitor of JAK1 and is used mainly for rheumatoid arthritis. However, it has received a black box warning for its potential toxicities. Other examples of agents of this type include oclacitinib (ApoquelTM), used for the control of pruritus associated with allergic dermatitis; peficitinib (SmyrafTM), which mainly inhibits JAK3 and is used for treatment of rheumatoid arthritis; and fedratinib (InrebicTM), a JAK2 inhibitor used for the treatment of primary or secondary myelofibrosis.
The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis
Published in Journal of Dermatological Treatment, 2023
Teppei Hagino, Hidehisa Saeki, Eita Fujimoto, Naoko Kanda
This study has several limitations. We could not compare the treatment responses to upadacitinib among individual features of rash, erythema, induration/papulation, excoriation, and lichenification. The differential treatment responses among different features of rash should be examined in further studies. Second, this study evaluated only the therapeutic effects of 15 mg/day of upadacitinib, and not of 30 mg/day, which should be examined in further studies. Third, there is a lack of information on the dose and rank of topical corticosteroids used for different anatomical sites. Treatment responsiveness might be affected by the dose and rank of corticosteroids, which might influence the anatomical site-dependent differences in treatment responsiveness. For instance, it is common to apply less potent corticosteroids to the face, which may result in the lower treatment response of the head and neck rash compared to that of the other sites. Therefore, future studies should record the detailed information about the topical corticosteroids for individual anatomical sites.
The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease
Published in Expert Review of Clinical Immunology, 2023
Nancy Gupta, Sam Papasotiriou, Stephen Hanauer
Serious infections are defined as infections that are life-threatening or require intravenous antibiotics or hospitalization. In the 8-week OCTAVE induction trial with 10 mg twice daily tofacitinib, the risk of serious infection was higher with tofacitinib than placebo. In the 52 weeks, the OCTAVE Sustain maintenance trial, the rate of serious infection was similar across all three groups (10 mg twice daily tofacitinib, 5 mg twice daily tofacitinib, and placebo) [14]. In the 7-year OCTAVE Open, the incident rate of serious infections was higher with tofacitinib 10 mg twice daily at 1.74 (95% CI 1.18–2.47) per 100 patient-years compared to 1.25 (95% CI 0.54–2.46) per 100 patient-years with 5 mg twice daily tofacitinib [15]. In the induction and maintenance clinical trials of upadacitinib, the risk of serious infections was similar across all doses of upadacitinib (45 mg, 30 mg, and 15 mg) and placebo [22].
Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2023
Ariana Moreno, Yael Renert-Yuval, Emma Guttman-Yassky
Upadacitinib, an oral JAK inhibitor, is currently approved for the treatment of pediatric AD in patients 12 years and older with refractory moderate-to-severe AD [128]. Pediatric patients (>12) receiving upadacitinib achieved EASI-90 and EASI-100 by week 16 of treatment [129]. Additionally, fewer patients receiving upadacitinib reported AD flares compared to placebo at week 16 [129]. Furthermore, upadacitinib groups demonstrated significant improvements in ADerm-IS sleep domain, ADerm-IS daily activities, ADerm-IS emotional state, anxiety, depressiondepression, and quality of life assessment scores compared to placebo [129]. Results from an ongoing phase III clinical trial showed the efficiency and safety of upadacitinib with TCS in adolescent and adult patients [130], with 50.8% and 69% of patients receiving upadacitinib 15 mg and 30 mg (with TCS for both) achieving EASI-75, respectively. 33.5% and 45.2% of the 15 mg upadacitinib+TCS group and 30 mg upadacitinib+TCS achieved IGA scores of 0/1, respectively. With regard to NRS improvements, 45.3% and 57.5% of the 15 mg upadacitinib+TCS and 30 mg upadacitinib+TCS achieved >4 points improvement on NRS scores [130]. The most frequently reported adverse effects in the lower upadacitinib dose included nasopharyngitis (17.2%), acne (14%), upper respiratory tract infections (URI) (10.2%), blood creatinine phosphokinsase (CPK) increases (8.4%), and headache (6.5%) [130].