Plain Language Summary of the PAISLEY study: deucravacitinib as a treatment for people with systemic lupus erythematosus.

What is this summary about?This plain language summary describes the results of the phase 2 study called PAISLEY which tested deucravacitinib, a new medicine under investigation before approval, in people living with lupus. In this trial, researchers wanted to find out if deucravacitinib would be safe and reduce the symptoms and disease activity in people living with lupus. PAISLEY looked at the type of lupus known as systemic lupus erythematosus, shortened to SLE.What happened in the study?The study included 363 people from 17 countries who had SLE and were between 18 and 75 years of age. The participants were divided into 4 groups at random. One group was given placebo (a fake or dummy pill that contains no medicine) and the other 3 groups took deucravacitinib, a pill taken by mouth. Each of the groups taking deucravacitinib took a different dose, either 3 milligrams (mg) twice daily, 6 mg twice daily, or 12 mg once daily. After 32 and 48 weeks, researchers measured the number of people in each group who had improvements in their SLE symptoms and disease activity, as measured by different tests. They also looked at any side effects people experienced, which may or may not have been caused by the medicine.What do the results mean?After 32 weeks of treatment, SLE symptoms and disease activity improved in more people in each of the deucravacitinib dose groups compared with the people taking placebo (the dummy pill). After 48 weeks of treatment, SLE symptoms and disease activity were still improved in more people taking deucravacitinib compared with people taking placebo, and this was measured in several different ways. The best results were seen in people taking deucravacitinib 3 mg twice daily. The number of serious side effects was similar for people taking deucravacitinib and those taking placebo. The most common side effects that were seen in people taking deucravacitinib were infections such as sore throat, cough, or bronchitis (upper respiratory tract), infltion in the nose (nasopharyngitis), headaches, and urinary tract infections. More people taking deucravacitinib than placebo had acne, rash, and cold sores (oral herpes). These were not serious and did not have any long-term effects on patient health or lead to patients stopping treatment.How to say (double click sound icon to play sound)… Systemic lupus erythematosus: SIS-teh-MIC LOO-puhs Eh-RE-the-ma-TOE-susDeucravacitinib: doo-KRAV-a-sih-ti-nibEnzyme: EN-zimeInterferon: in-tur-FER-onPlacebo: pluh-SEE-bohTyrosine kinase: TY-ruh-seen KY-naysTYK2: TIK-tu.

Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE). METHODS: Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI-4) response at week 32. Secondary outcomes assessed at week 48 included SRI-4, British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts. RESULTS: At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported. CONCLUSION: Deucravacitinib treatment elicited higher response rates for SRI-4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids.

Uterine fibroids feature excessive deposition of types I and III collagen. Previous ex vivo studies showed an FDA-approved collagenase (EN3835)-digested types I and III collagen fibers in fibroid tissues; however, collagenase had not been evaluated in vivo for effects on uterine fibroids. The objective was to assess the safety and tolerability of collagenase injection directly into uterine fibroids. This was a prospective, open label, dose escalation study. The study participants were fifteen women aged 35-50 years with symptomatic uterine fibroids planning to undergo hysterectomy. Three subjects received saline and methylene blue, three subjects received a fixed dose of EN3835, and 9 subjects received stepped, increasing dosages of EN3835, all by transvaginal, ultrasound-guided injections. Primary outcome measures were safety and tolerability of the injection and change in collagen content between treated and control tissues. There were no significant adverse events following injection of EN3835 into uterine fibroids. Masson's trichrome stains revealed a 39% reduction in collagen content in treated samples compared to controls (p <0.05). Second harmonic generation (SHG) analysis showed treated samples to have a 21% reduction in density of collagen compared to controls. Picrosirius-stained collagenase-treated fibroids showed collagen fibers to be shorter and less dense compared to controls. Subjects reported a decrease in fibroid-related pain on the McGill Pain Questionnaire after study drug injection in Group 2 at both 4-8 days and 60-90 days post-injection. The findings indicated that injection of collagenase was safe and well tolerated. These results support further clinical investigation of collagenase as a minimally invasive treatment of uterine fibroids. NCT0289848.