The efficacy and safety of low-dose rituximab in the treatment of pemphigus vulgaris: a cohort study.

BACKGROUND: Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved. OBJECTIVES: To investigate the efficacy and safety of low-dose RTX (a single infusion of 500 mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX. METHODS: Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected. RESULTS: Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone. CONCLUSIONS: This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV.

Association of gut microbiome and metabolites with onset and treatment response of patients with pemphigus vulgaris.

Background: Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV. Methods: We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis. Results: The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid). Conclusions: This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.

Efficacy, Safety, and Pharmacoeconomic Analysis of Adalimumab and Secukinumab for Moderate-to-Severe Plaque Psoriasis: A Single-Center, Real-World Study.

INTRODUCTION: A growing number of biologics have recently been approved in China for psoriasis treatment, and some of these are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. Nevertheless, real-world data on the efficacy and safety of biologics for treating moderate-to-severe plaque psoriasis in Chinese patients are limited, and relevant pharmacoeconomic studies are lacking. Therefore, we performed a prospective, single-center study to evaluate the efficacy and safety of adalimumab (ADA) and secukinumab (SEC) in real-world practice. A cost-effectiveness analysis (CEA) was also conducted. METHODS: Participants were enrolled between January 2019 and December 2020 at the West China Hospital, Sichuan University. Baseline and follow-up assessments were conducted, and an appropriate statistical analysis was performed. RESULTS: A total of 183 patients were included. At week 12, the number of patients achieving a psoriasis area and severity index reduction of 75% (PASI 75) with SEC treatment was higher than that with ADA and methotrexate (MTX) (SEC versus ADA versus MTX, 90.59% versus 58.70% versus 17.14%, respectively). Adverse events (AEs) were reported in 44.83% and 56.36% of patients in the SEC and ADA groups, respectively. The cost-effectiveness ratio in the SEC group was 46,311.83 Chinese yuan(CNY), compared with 17,580.92 CNY in the ADA group. CONCLUSION: In real-world practice, SEC and ADA are effective and safe for moderate-to-severe plaque psoriasis treatment in Chinese patients. On the basis of drug prices during our study period without considering access to health insurance, ADA was more cost-effective in real-world practice. Adalimumab and secukinumab are two monoclonal antibodies used for the treatment of psoriasis, which target different cytokines in the pathogenesis. A growing number of biologics have recently been approved in China for psoriasis treatment including adalimumab and secukinumab, which are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. With the purpose of evaluating its efficacy and safety in the real world, we registered the data of eligible patients in West China Hospital, Sichuan University over the past two years and conducted statistical analysis. In order to provide different therapeutic strategies for patients based on case-specific needs and access to financial resources, we performed pharmacoeconomic analyses to evaluate the cost-effectiveness of the two drugs. Our study demonstrated that adalimumab and secukinumab were effective and safe for moderate-to-severe plaque psoriasis in Chinese patients in the real-world practice. Based on drug prices during our study period and without taking into consideration access to health insurance, ADA was more cost-effective in real-world practice.

Effect of NUDT15 polymorphisms on early hematological safety of low-dose azathioprine in Chinese patients with pemphigus vulgaris: A prospective cohort study.

Azathioprine (AZA) is the preferred immunosuppressant for treating pemphigus vulgaris (PV), with discontinuation mainly attributed to hematological adverse events (AE). Reportedly, nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) polymorphisms have been strongly associated with thiopurine-induced leukopenia. To investigate hematological AE of low-dose AZA based on NUDT15 genotypes among patients with PV, a prospective cohort study was conducted in patients with PV, followed-up for the first 8 weeks after AZA administration. All patients were divided into wild homozygous and heterozygous NUDT15 groups. Both groups initiated AZA at low dose (50 mg/day) and continued with different dose-escalating approaches. Bone marrow suppression was considered the principal outcome. Overall, 62 patients with PV were enrolled (48 in the wild homozygous NUDT15 group vs. 14 in the heterozygous NUDT15 group). Except for median maintenance doses of AZA, no statistically significant differences were observed between the two groups in terms of age, sex, white blood cells, neutrophil count, platelet count, hemoglobin level, median final doses of corticosteroids (mg prednisone equivalent), pemphigus disease area index, and anti-desmoglein 1/3 autoantibodies. In both groups, patients presented similar hematological AE and treatment responses after administration of different low-dose AZA treatment strategies. Low-dose AZA based on NUDT15 genotypes can reduce the risk of early hematological AE among patients with PV.

Complete remission of refractory pemphigus vulgaris in a Chinese patient with mutated NUDT15 by combination of minimal doses of azathioprine and prednisone.

Although azathioprine (AZA) combined with corticosteroids remains the first-line therapy to treat patients with pemphigus vulgaris (PV), there are increasing reports of AZA-induced leukopenia, which provides the rationale for monitoring the blood cell count and testing the genotypes at the thiopurine methyltransferase (TPMT) and the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes. Here, we reported a case of persistent refractory PV in a Chinese patient with three runs of AZA-corticosteroids treatment. In the first two runs he received AZA-corticosteroids at standard or slightly reduced doses and developed leukopenia. In the third run of treatment, he was found to have NUDT15 mutation (rs116855232) and wild-type homozygous TPMT*3C (rs1142345), treatment with minimal doses of AZA and prednisone resulted in a complete remission of PV without any side effects including leukopenia. Our observations not only highlight the benefits of testing the TPMT and NUDT15 genotypes and monitoring the dynamic changes of the white blood cell count in guiding the AZA therapy, but also suggest the potential of using the AZA-corticosteroids combination at very low doses in the treatment of refractory PV.