Vonoprazan-amoxicillin dual therapy with different amoxicillin dosages for treatment-naive patients of Helicobacter pylori infection in China: a prospective, randomized controlled study.

BACKGROUND: The vonoprazan (VPZ)-amoxicillin (AMO) dual therapy (VA) demonstrates a satisfactory eradication rate for Helicobacter pylori (H. pylori ). However, the optimal dosage of AMO in this regimen remains uncertain. The objective of this study is to investigate the efficacy of different doses of AMO in the VA regimen for first-line treatment of H. pylori infection. METHODS: A total of 192 treatment-naive H. pylori -infected patients were randomly assigned to one of three groups: low-dose VA (LD-VA: VPZ 20 mg b.i.d + AMO 750 mg t.i.d), moderate-dose VA (MD-VA:VPZ 20 mg b.i.d + AMO 1000 mg t.i.d), and high-dose VA (HD-VA: VPZ 20 mg b.i.d + AMO 1250 mg t.i.d). All groups received 14 days of treatment. The study evaluated and compared the eradication rates, adverse events (AEs), and patient compliance among the three groups. RESULTS: Eradication rates for LD-VA, MD-VA, and HD-VA were 76.6% (49/64), 79.7% (51/64), and 84.4% (54/64), respectively, as determined by intention-to-treat analysis; 90.6% (48/53), 94.3% (50/53), and 98.1% (53/54) according to per-protocol analysis; 89.1% (49/55), 94.4% (51/54), and 96.4% (54/56) with modified intention-to-treat analysis (all P  > 0.05). Although not statistically significant, numerically higher eradication rates were observed with the higher dose AMO VA regimen. There were no statistically significant differences in the incidence of AEs and compliance among the three VA regimens. CONCLUSION: Fourteen-day VA regimens with AMO doses exceeding 2 g/day demonstrated satisfactory eradication rates. HD-VA therapy is potentially the most effective regimen. Large-sample clinical trials are required to further validate these findings.

Meta-analysis of Helicobacter pylori eradication therapy using vonoprazan as an acid suppressor compared with bismuth quadruple therapy.

BACKGROUND: Vonoprazan, a novel acid suppressant, has recently emerged as a regimen for eradicating Helicobacter pylori. However, uncertainties exist about the effectiveness and safety of VPZ-based regimens compared with those of bismuth-based quadruple therapy in eradicating H. pylori. The present meta-analysis was performed to compare the effectiveness and safety of vonoprazan-based regimens with those of bismuth quadruple therapy in eradicating H. pylori. MATERIALS AND METHODS: All randomized controlled trials and non-randomized controlled trials comparing the vonoprazan-based therapy with the bismuth quadruple therapy were included in this meta-analysis. Information was also extracted by two evaluators, and if heterogeneity existed, a random-effects model was used to calculate the combined relative ratio and 95% confidence interval; otherwise, a fixed-effects model was used. And subgroup analyses were performed to explore the sources of heterogeneity. RESULTS: A total of 10 studies, comprising 2587 patients were included in the meta-analysis. The results showed that the combined eradication rate of patients treated with the vonoprazan-based regimen was significantly higher than that of patients treated with bismuth quadruple therapy, in both intention-to-treat and per-protocol analyses, and the differences were statistically significant. Among the intention-to-treat analyses results: (90.28% vs. 83.64% [odds ratio (OR) = 1.85, 95% confidence interval (CI) (1.27, 2.70), p = 0.001]); in the per-protocol analyses: (94.80% vs. 89.88%, [OR = 2.25, 95% CI (1.37, 3.69), p = 0.001]). The occurrence of adverse events was significantly lower in patients treated with vonoprazan-based regimens than in those treated with bismuth quadruple therapy, (14.50% vs. 25.89%, [OR = 0.49, 95% CI (0.32, 0.75), p = 0.001]). CONCLUSIONS: For eradicating H. pylori, vonoprazan-based regimens are remarkably advantageous over bismuth quadruple therapy. Furthermore, vonoprazan-based regimens exhibit a lower rate of adverse events than bismuth quadruple therapy.

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Left Ventricular Hypertrophy (ESES-LVH) Study: A Multicenter, Open-Label, Prospective, Interventional Study.

INTRODUCTION: In contrast to the antihypertensive effect of esaxerenone, there is little evidence of its cardioprotective effect. We investigated the efficacy and safety of esaxerenone in patients with uncontrolled hypertension and left ventricular hypertrophy taking a renin-angiotensin system inhibitor (RASi) or calcium-channel blocker (CCB). METHODS: This was a multicenter, open-label, exploratory study with a 24-week treatment period. Esaxerenone was orally administered at an initial dose of 2.5 mg/day (maximum dose: 5 mg/day). The primary endpoints were the change in morning home systolic blood pressure (BP)/diastolic BP and change and percentage change in left ventricular mass index (LVMI) from baseline to end of treatment (EOT). Key secondary endpoints included change from baseline in bedtime home and office BP, achievement rate of target BP, and safety. RESULTS: In total, 60 patients were enrolled. Morning home systolic/diastolic BP was significantly decreased from baseline to EOT in the total population (- 11.5/ - 4.7 mmHg, p < 0.001) and in both the RASi and CCB subcohorts (all p < 0.01). Significant reductions in bedtime home and office BP were shown in the total population and both subcohorts. LVMI was also significantly decreased from baseline to EOT in the total population (- 9.9 g/m2, - 8.5%, both p < 0.001) and both subcohorts (all p < 0.05). The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 35.0% and 3.3%, respectively; most were mild or moderate. No new safety concerns were identified. CONCLUSION: Esaxerenone showed favorable antihypertensive and cardioprotective effects and safety in hypertensive patients with cardiac hypertrophy. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs071190043).

Vonoprazan: A Review in Helicobacter pylori Infection.

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Infection with the bacterium Helicobacter pylori is a leading cause of peptic ulcer disease and has been identified as an important risk factor for gastric cancer. Current recommended treatments for H. pylori infection generally involve a combination of antibiotics together with an acid suppressant, such as a proton-pump inhibitor (PPI). However, treatment success rates with current guideline-recommended PPI-based regimens remain suboptimal. Vonoprazan (Voquezna^®), from a new class of drugs known as potassium-competitive acid blockers, has the potential to provide potent and sustained acid suppression. Based on the findings of a pivotal trial (PHALCON-HP) conducted in the USA and Europe, vonoprazan is now approved in the USA for the treatment of H. pylori infection in adults when used in combination with amoxicillin, or amoxicillin and clarithromycin. Alongside the demonstrated efficacy and tolerability of the vonoprazan-based regimens, vonoprazan has a rapid onset of action and can be taken with or without food. Thus, vonoprazan-based dual and triple therapy regimens present valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Investigation of Gastrointestinal Toxicities Associated with Concurrent Abdominal Radiation Therapy and the Tyrosine Kinase Inhibitor Sunitinib in a Mouse Model.

Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control; however, increased incidences of gastrointestinal (GI) toxicity have been reported with this combination. We hypothesize that toxicity is due to compromised intestinal healing caused by inhibition of vascular repair and proliferation pathways. This study explores underlying tissue toxicity associated with abdominal RT and concurrent sunitinib in a mouse model. Four groups of CD-1 mice were treated with 12 Gy abdominal RT, oral sunitinib, abdominal RT + sunitinib, or sham treatment. Mice received oral sunitinib or the vehicle via gavage for 14 days. On day 7, mice were irradiated with 12 Gy abdominal RT or sham treated. Mice were euthanized on day 14 and intestinal tract was harvested for semiquantitative histopathologic evaluation and immunohistochemical quantification of proliferation (Ki67) and vascular density (CD31). Non-irradiated groups had stable weights while abdominal irradiation resulted in weight loss, with mice receiving RT + SUN having greater weight loss than mice receiving RT alone. Semiquantitative analysis showed significant increases in inflammation in irradiated groups. The difference in the density of CD31+ cells was significantly increased in RT alone compared to SUN alone. Ki67+ density was not significant. In summary, we identify a lack of angiogenic response in irradiated GI tissues when abdominal RT is combined with a TKI, which may correlate with clinical toxicities seen in canine and human patients receiving combined treatment.

Exposure-response analysis of the efficacy and safety of esaxerenone, a novel nonsteroidal mineralocorticoid receptor blocker, in hypertensive patients with or without diabetic kidney disease.

BACKGROUND: Esaxerenone is a novel non-steroidal mineralocorticoid receptor blocker. Here, we assessed efficacy and safety exposure-response relationships of esaxerenone and its covariates and thereby justified the recommended dosage regimens, focusing on the safety benefits of up-titration regimen in patients at higher risk for increased serum potassium (sK+). METHODS: The relationships between model-derived individual esaxerenone exposure and efficacy (blood pressure [BP]) and safety (increased sK+) were evaluated using multivariate linear regression and Cox regression analyses, respectively, using data from 1453 hypertensive patients with or without diabetic kidney disease in five clinical studies. RESULTS: Exposure-efficacy analyses demonstrated that higher exposure was linearly associated with greater BP reduction over the investigated dose range. Exposure-safety analyses showed that higher exposure was associated with a higher risk of increased sK+ under a fixed-dosing regimen; higher baseline sK+ and lower baseline estimated glomerular filtration rate (eGFR) were influential covariates. Model-based simulations suggested that fewer occurrences of increased sK+ are expected under the up-titration regimen (from 1.25 to 5 mg) relative to the fixed-dosing regimen (5 mg) in patients with different combinations of these covariates. CONCLUSIONS: The exposure-response analyses supported the esaxerenone recommended doses and the safety benefits of using the up-titration regimen.

A systematic review and meta-analysis of the efficacy of vonoprazan for proton pump inhibitor-resistant gastroesophageal reflux disease.

BACKGROUND AND AIM: Up to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI-resistant or refractory GERD. Vonoprazan, a potassium-competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta-analysis summarizes the efficacy and safety of vonoprazan for treating PPI-resistant GERD (both erosive esophagitis [EE] and non-erosive reflux disease [NERD]). METHODS: Four electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI-resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle-Ottawa Scale (NOS) was used to assess study quality. RESULTS: Twelve studies were included in this meta-analysis. Healing rates of PPI-resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8-94.8%) and 88.5% (95% CI 69.7-96.2%) at weeks 4 and 8, respectively. For healed PPI-resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2-95.0%) at week 8, 86.0% (95% CI 72.1-94.7%) at week 24, and 93.8% (95% CI 69.8-99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8-81.7%) and 51.9% (95% CI 37.8-65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported. CONCLUSION: Vonoprazan demonstrated high efficacy in the healing and maintenance of PPI-resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI-resistant GERD patients.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.

BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%). CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Six-month safety and effectiveness of tofacitinib in patients with rheumatoid arthritis in Japan: Interim analysis of post-marketing surveillance.

OBJECTIVES: We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. METHODS: This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. RESULTS: Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. CONCLUSIONS: In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. STUDY IDENTIFIER: NCT01932372.

Upfront tofacitinib in patients with biological-naïve ulcerative colitis - An Indian multicentric experience.

OBJECTIVES: Tofacitinib is a Janus Kinase inhibitor used for treating moderate to severe ulcerative colitis (UC), mainly after the failure of biological therapy. There is a paucity of data on the outcome of tofacitinib in biological-naïve UC patients. The present study was aimed at analyzing the safety and efficacy of tofacitinib in biological-naïve Indian patients with UC. METHODS: The present study retrospectively evaluated consecutive patients with biological-naïve moderate-to-severe active UC from six tertiary care centers in India receiving tofacitinib from September 2020 to September 2022. Clinical remission or response assessment was based on partial Mayo score (PMS) calculated at baseline and weeks eight, 16 and 24. RESULTS: Total 47 cases (57.4% male, median age: 32 years) were included. After eight weeks of therapy, 33 (70.2%) achieved clinical remission and eight (17.0%) had a primary failure. The baseline serum albumin at treatment initiation was the only independent predictor of remission at eight weeks (Odds ratio: 11.560, 95% CI: 1.478 - 90.404), but not at 16 weeks. By 24 weeks, 59.6% (28/47) of the patients were in remission and 29.8% (14/47) had stopped tofacitinib either due to failure (27.6%) or adverse events (AEs) (2.1%). Among the 47 patients, 10 (21.2%) cases developed AEs during follow-up, including two tuberculosis (4.2%), one cytomegalovirus (CMV) colitis (2.1%) and one herpes zoster (2.1%). Four patients with infection required temporary drug discontinuations. One required permanent discontinuation (mania). CONCLUSION: Upfront tofacitinib is effective in biologic-naïve Indian patients with moderate-severe UC. Further randomized studies are required to validate the study findings.

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system.

BACKGROUND: Migraine has a high prevalence in the population and accounts for 12% of primary headaches. Ubrogepant is used for the treatment of acute migraine, and although some clinical trials have demonstrated the safety of Ubrogepant, its long-term safety in a large sample of the population remains to be investigated. METHODS: We collected data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC) and the empirical Bayes geometric mean (EBGM) to evaluate Ubrogepant-induced adverse events (AEs). RESULTS: We screened out 2,067 reports of Ubrogepant as primary suspected (PS) and 6,190 reports of Ubrogepant-induced AEs as PS. Our results showed that Ubrogepant-induced AEs targeted 4 system organ classes (SOCs), detected 32 Preferred terms (PTs) signals in 9 SOCs, including common Ubrogepant label consistent with Migraine, Nausea, Somnolence, Paraesthesia oral and Dizziness, It also includes the AEs of Hemiparesis, Mental impairment, Dysstasia, Tinnitus, Chest pain, Cold sweat, Neck pain, etc. that have not been demonstrated in previous studies. CONCLUSIONS: Our study identified new AEs that have not been reported, which provides a new guidance to deepen the comprehension of the safety of Ubrogepant.

Effectiveness of oral tofacitinib treatment on patients with moderate-to-severe alopecia areata in Iran.

INTRODUCTION: Alopecia areata is an inflammatory hair loss and a common autoimmune disease. Conducting treatment studies on alopecia areata is difficult due to unpredictable periods and even spontaneous recovery from the disease. In this study, the effectiveness of tofacitinib in treating alopecia areata was investigated. MATERIALS AND METHODS: The severity of the disease was evaluated using the Alopecia Severity Tool (SALT), and based on the medical history and patient's documents and photos, the score before and after the treatment was obtained. The patients were prescribed tofacitinib tablets at a dose of 5 mg twice a day for at least 6 months and were followed for a minimum of 18 months. RESULTS: No side effect was observed in 97.9% of the patients. After 6 months, except for three patients who did not need any maintenance dose, others needed an average daily intake of 7 mg of tofacitinib. After 18 months, the hair loss decreased by 6.45 times compared to the beginning and by 0.5 times compared to the end of 6 months (p < 0.05). In addition, it was found that body hair loss decreased 4 times compared to the beginning and 0.6 times compared to the end of 6 months (p < 0.05). The reduction of nail involvement after 18 months and 6 months was 1.2 times and 0.6, respectively, (p < 0.05). CONCLUSION: Treatment of alopecia areata with tofacitinib is recommended due to its effectiveness in reducing hair loss on the head, body, and nail involvement with few reversible side effects.

ToRaRI (Tofacitinib in Rheumatoid Arthritis a Real-Life experience in Italy): Effectiveness, safety profile of tofacitinib and concordance between patient-reported outcomes and physician's global assessment of disease activity in a retrospective study in Central-Italy.

INTRODUCTION: The use of Janus Kinase Inhibitors (JAK-Is) in rheumatoid arthritis (RA) has entered in daily practice. In consideration of ORAL-Surveillance trial and the new EULAR recommendations, real-world data are needed to assess Jak-Is safety and effectiveness. The multicenter study presented here aimed to evaluate effectiveness and safety of tofacitinib in a real-life cohort. METHODS: A retrospective analysis was performed from September 2021 to December 2022. Data were collected when tofacitinib was started (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. The primary objective was to analyze the efficacy and safety of tofacitinib. Safety was assessed by recording adverse events (AEs) with and without discontinuation. The secondary objective was to assess the difference between Patient-Reported Outcomes (PROs) and Physician's Global Assessment of disease activity (PhGA). RESULTS: 122 patients were included in the study from the following rheumatology Centers: Pisa, Ancona, Florence (two Centers), Siena, and Sardinia. A statistically significant improvement in DAS-28-CRP, CDAI and SDAI score was observed at T3, T6, compared to baseline (p < 0.001). Improvement was confirmed in patients who reach T12. Patients naïve to bDMARDs showed a shorter remission time and higher remission rates. There was also a statistically significant improvement in PROs compared to baseline (p < 0.001). The improvement was rapid and was consistent with PhGA. The 12-month retention rate for tofacitinib was 89.35%. Reasons to stop tofacitinib were: insufficient response (7), gastrointestinal symptoms (2), infection (1), malignancy (1), Zoster (1), pruritus sine materia (1). CONCLUSIONS: Tofacitinib is safe and effective in our RA cohort. It induces higher remission rates in patients naive to bDMARDs, suggesting that there may be a benefit using it as first-line therapy. Additionally, improvement in PROs was consistent with PhGA scores, demonstrating how tofacitinib affects both the objective and subjective components of disease activity. Key Points 1. JAK inhibitors are considered at a similar level as biologic agents in terms of effectiveness. 2. After ORAL-Surveillance results, real-world data are needed to assess the benefit/risk profile of Jaki. 3. Disagreement between patients and physicians has been previously reported with biologic therapy among patients with rheumatoid arthritis, with patients rating disease activity higher than physicians. 4. Jak inhibitors could reduce this discrepancy, due to their mechanism of action.

Different dosages of vonoprazan for gastroesophageal reflux disease: study protocol for a pragmatic, crossover-cluster, randomized controlled trial with patient preference arms.

BACKGROUND: Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD. METHODS: This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit. DISCUSSION: This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION: https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023. PROTOCOL VERSION: February 18, 2023, Version 2.

Effectiveness and Predictive Factors of Response to Tofacitinib Therapy in 125 Patients with Alopecia Areata: A Single-centre Real-world Retrospective Study.

Alopecia areata is an autoimmune disorder that greatly impacts patients' quality of life, and its management remains challenging. Tofacitinib is the first Janus kinase inhibitor to be approved for clinical use and is the most extensively studied. Several studies have demonstrated the clinical effectiveness of oral tofacitinib in treating patients with alopecia areata. However, despite being widely used in clinical practice, no prospective randomized controlled trials have been implemented and its indication criteria have not been thoroughly established. Moreover, little is known about the factors associated with response to therapy under real-world conditions. The aims of this retrospective cohort study of patients with alopecia areata treated with tofacitinib for 3 months were to assess the effectiveness of tofacitinib and to identify predictive factors of response to it. Primary outcome was the change in disease severity, as evaluated by Severity of Alopecia Tool (SALT) grade. A total of 125 patients with alopecia areata were included, the incidence of effectiveness was 83.2%, and 16.0% of patients achieved a result of complete remission. Total duration of alopecia areata and previous hair regrowth were independent predictors of response. Combined therapy was associated with relapse after discontinuation. No severe adverse event was observed. This study suggests that tofacitinib provides an effective treatment option for patients with alopecia areata, and that earlier intervention in the treatment of severe alopecia areata with tofacitinib may lead to better outcomes.

Comparison of the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in the treatment of patients with hyperlipidaemia.

OBJECTIVES: To compare the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in reducing blood lipid levels. METHODS: Patients with hyperlipidaemia admitted to the cardiac centre between January 2019 and December 2020 were included in the study. A total of 1063 patients with hyperlipidaemia took either Shanhuang Jiangzhi tablets (n = 372) or atorvastatin (n = 691) and met the inclusion and exclusion criteria. Clinical data, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol, were retrospectively evaluated after propensity score matching (PSM) analysis. The adverse events were also recorded during the therapy process. RESULTS: Following PSM analysis, both groups were well matched across all parameters. Compared with the baseline, Shanhuang Jiangzhi tablets had greater effects on TC, TG and LDL-C, and the difference was statistically significant (p < 0.001). Furthermore, the results showed that Shanhuang Jiangzhi tablets are similar to atorvastatin in reducing TC and LDL-C, and all p-values were > 0.05. However, the decrease of TG was greater in the Shanhuang Jiangzhi group (p < 0.001). Clinical adverse reactions of Shanhuang Jiangzhi tablets are rare and have no statistical significance compared with atorvastatin (p = 0.682). CONCLUSIONS: Shanhuang Jiangzhi tablets have a higher hypotriglyceridaemic performance than atorvastatin and an equivalent ability to lower TC and LDL-C. In addition, Shanhuang Jiangzhi tablets are a low-risk option for lowering blood lipids.