pemphigus
Conditions
Interventions
experimental group:Administered with prednisone acetate at a dosage of 1mg/kg/day and tofacitinib at a dosage of 5mg twice daily for disease control.
Sponsors
The First Affiliated Hospital of Army Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Between the ages of 18 and 75 (for fertile women and men, effective contraception is required during treatment and for one month after Tofacitinib treatment is stopped). 2.Informed consent has been signed. 3. Bullous pemphigoid has been diagnosed within the last 24 months using the following diagnostic criteria: 1) :Clinical manifestations: ? Loose, tense bullae and large blisters appear on the skin, easily rupturing; ? Persistent erosions form after the rupture of bullae and blisters; ? Blisters or erosions develop on mucous membranes; ? Positive Nikolsky sign. 2):Histopathology: Desquamation of epidermal or epithelial cells, forming vesicles and bullae. 3):immunological criteria: ? DIF on the affected area or normal skin around the lesion shows IgG and/or complement deposition in the intercellular spaces of the epidermal (or epithelial) cells; ? IIF detects the presence of anti-intercellular antibodies in the serum; ? ELISA detects the presence of anti-Dsg1/3 antibodies in the serum. 4. There is significant disease activity, as defined by the following criteria: the Pemphigus Disease Area Index (PDAI) for skin or mucous membrane pemphigus is at least 3 in both areas, and the PDAI is between 15 and 45 (= 15 but = 45). 5. According to the "Expert Consensus on Diagnosis and Treatment of Pemphigus Vulgaris (2020)", refractory disease is defined as follows: For patients with pemphigus vulgaris, after 3 weeks of treatment with an adequate dose (1.5g/kg/d, calculated as prednisone) of glucocorticoids, combined or not combined with immunosuppressive agents (including cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, etc.) for 12 weeks, there are still new erythematous plaques or blisters present or the existing skin lesions continue to expand without healing. 6. The patient's prednisone dose at enrollment was required to be = 1mg/kg/d and maintained at a stable level for a minimum of 2 weeks.
Exclusion criteria
Exclusion criteria: ?. Diagnosis or evidence of suspected pemphigus vulgaris, paraneoplastic pemphigus, IgA pemphigus, drug-induced pemphigus, and other non-bullous pemphigoid-like autoimmune bullous diseases. ?. There is a documented history of allergic reactions to any investigational drugs. ?. During the period of pregnancy, lactation, or while planning to conceive throughout the study duration. ?. Patients who have taken JAK inhibitors orally within 8 weeks prior to enrollment, or who have not had a sufficient improvement in their condition with previous oral JAK inhibitor treatment. ?. Basically or completely disabled, unable to take care of oneself almost or completely, such as bedridden. ?. Suffering from uncontrolled hypertension, with recurrent systolic blood pressure > 160mmHg or diastolic blood pressure > 100mmHg within a week. ?. Patients who have had any major surgery within 8 weeks of the screening, or require a major surgery during the study period. ?. Patients who exhibit low immunity and are considered by the researchers to pose an unacceptable risk for participation in the study. ?. Within the 12 weeks prior to enrollment, the patient has experienced any of the following: myocardial infarction, unstable angina, stroke, or heart failure (NYHA functional classification III/IV stage) ?. Individuals with a history of deep venous thrombosis (DVT) or who are considered to be at high risk for VTE, with 2 or more of the following VTE risk factors: 1) Age > 75 years; 2) BMI > 35 kg/m2; 3) Currently taking celecoxib, etoricoxib, contraceptive pills, or smoking. ?.Patients who have history of cardiovascular, respiratory, liver, gastrointestinal, endocrine, hematological, or neuropsychiatric disease, or any other serious and/or unstable condition. The investigator determines that participation in the study would have unacceptable risks or would compromise the reliability of the data. ?. A history of lymphomatous disease; or signs or symptoms suggestive of lymphomatous disease; or any history of malignant tumor (excluding localized basal cell carcinoma) within the past 5 years, regardless of whether treatment has been received. ?.Currently or recently have a serious viral, bacterial, fungal, or parasitic infection, including but not limited to the following: 1) A symptomatic herpes zoster infection within the past 12 weeks prior to enrollment; 2) A history of disseminated/complex herpes zoster (such as multi-dermatome involvement, ocular herpes zoster, or central nervous system involvement) or postherpetic neuralgia; 3) A current case of herpesvirus hominis infection at the time of enrollment; 4) Active or chronic infection with HBV, HCV, or HIV; 5) Evidence of active or latent tuberculosis, or previous evidence of active tuberculosis without receiving proper treatment; 6) A serious infection within the past 4 weeks or treatment with intravenous antibiotics for a serious infection. ?. Patients who have any serious condition except bullous pemphigoid that expected to require systemic glucocorticoids. ?. Have received or are scheduled to receive a live vaccine within the past 12 weeks. ?. Patients who have abnormal ECG findings, and after being evaluated by the researcher, it is determined that participation in the study has unacceptable risks. ?. The following specific abnormalities were noted on laboratory tests during screening: 1) ALT or AST > 2 times the upper limit of normal (ULN); 2) AIP > 2 times ULN; 3) TBL > 1.5 times ULN; 4) Hemoglobin <
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants who achieved complete disease remission by week 24; | — |
Secondary
| Measure | Time frame |
|---|---|
| The improvement in BPDAI activity scores at weeks 0, 2, 4, 8, 12, 16, 20, and 24 for the participants;The time it takes for the participant to reach complete remission from the baseline;The number of recurrences experienced by the participants during the treatment period.;The time of relapse during the course of treatment for the participants.;The cumulative dose of prednisone used during the course of treatment.;The levels of Dsg1 and Dsg3 in the participants changed at weeks 0, 4, 8, 12, 16, 20, and 24.;The levels of serum IL-4,IL-7,IL-9,IL-15 and IL-21 in the participants were measured using the ELISA method at baseline and during complete remission.;Using immunohistochemistry methods to detect the levels of pJAK1, pJAK3, pSTAT3, and pSTAT6 at the same skin lesion site in participants at baseline and complete remission.;The differences in transcriptome changes at the same lesion site between baseline and complete remission were analyzed using RNA-seq method.; | — |
Countries
China
Contacts
Public ContactMingwang Zhang
The First Affiliated Hospital of Army Military Medical University
Outcome results
None listed