Bullous pemphigoid
Conditions
Interventions
Test group:Patients enrolled in the study were administered with prednisone acetate at a dosage of 0.5mg/kg/day and tofacitinib at a dosage of 5mg twice daily for disease control.
Sponsors
Department of Dermatology, 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: During the non-vesicular stage, patients typically present with erythematous or urticarial plaques, often accompanied by intense pruritus. Subsequently, tense blisters and bullae may develop on normal-appearing skin or within areas of urticarial erythema. Notably, there is a negative Nikolsky sign and minimal or no involvement of oral or genital mucosa. 2)Histopathology: Fresh blisters exhibited subepidermal blister formation with varying degrees of eosinophil and/or neutrophil infiltration. Eosinophils and neutrophils were predominantly observed infiltrating the superficial dermis. The non-vesicular stage lacks specificity, occasionally presenting only subepidermal fissures and eosinophilic spongiosis. 3)immunological criteria: ? DIF: Fresh vesicle skin is taken from 1 cm around the edge, normal skin or erythema, and the basement membrane zone shows linear deposition of IgG and/or C3, with a few patients having linear deposition of IgA and/or IgE; ? IIF: Normal human skin frozen sections are used as substrates, and IgG autoantibodies that recognize the basement membrane zone are present in the patient's serum, distributed linearly. Salt-split IIF uses normal human skin as a substrate, and after 1 mol/L sodium chloride solution acts on the skin, the epidermis and dermis separate, and IgG antibodies bind linearly to the epidermis side. A diagnosis can be established by fulfilling the clinical and at least one of histopathological or immunohistochemical criteria 4. The Bullous Pemphigoid disease area index (BPDAI) ranges from 20 to 56 (=20 but =56). 5. :The definition of recalcitrant BP is as follows: After 1 month of regular treatment (maximum topical and oral steroids), patients still experience new erythema and vesicles every day, with a count of more than 5 per day. 6. The patient's prednisone dose at enrollment was required to be = 0.75mg/kg/d and maintained at a stable level for a minimum of 2 weeks.
Exclusion criteria
Exclusion criteria: ?. Diagnosis or evidence of consideration of mucous membrane pemphigoid, acquired epidermolysis bullosa, and other non-pemphigoid 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/m^2; 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 < 100g/L; 5) White blood cells <
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 improvement in BPDAI itching 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.;he 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 BP180 and BP230 in the participants changed at weeks 0, 4, 8, 12, 16, 20, and 24.;The levels of serum IL-4, IL-5, IL-6, IL-13, IL-17, IL-21, and IL-23 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