Tocilizumab for the Treatment of Refractory Granulomatous Lobular Mastitis

Inclusion criteria

• Females aged 20 to 50 years;
• Clinically diagnosed (combined with pathology) with non-lactational granulomatous mastitis (cessation of lactation for more than 6 months);
• M-Activity-Score ≥ 2;
• Steroid-refractory NL-GLM or intolerant to steroid therapy.
• Female subjects of childbearing potential agree to use highly effective contraception starting at least 7 days before the first dose until 16 weeks after dosing. Pregnancy tests for female subjects of childbearing potential must be negative within 7 days before the first dose.

Exclusion criteria

• Bilateral mastitis occurring simultaneously or sequentially within six months.
• Clinical diagnosis (combined with pathological findings) of periductal mastitis.
• History of lymphoproliferative disorder; or presence of signs or symptoms suggestive of a possible lymphoproliferative disorder (including lymphadenopathy or splenomegaly); or active primary or recurrent malignancy; or clinically significant malignancy with a remission duration of less than 5 years.

• Patients with carcinoma in situ of the cervix may participate if successfully treated with no evidence of recurrence or metastasis for at least 3 years.
• Patients with basal cell or squamous cell carcinoma of the skin may participate if successfully treated with no evidence of recurrence for at least 3 years.
• Patients who are pregnant.
• Current or recent severe viral, bacterial, fungal, or parasitic infection, including but not limited to:

• Symptomatic herpes zoster infection within 12 weeks prior to screening.
• History of disseminated/complicated herpes zoster (e.g., multidermatomal involvement, herpes zoster ophthalmicus, CNS involvement, or postherpetic neuralgia).
• Symptomatic herpes simplex at the time of enrollment.
• Active or chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Household contact with an individual with active tuberculosis (TB) and not having received appropriate and documented TB prophylaxis.
• Evidence of active TB, or history of active TB without appropriate and documented treatment.
• Clinically significant infection within 4 weeks prior to enrollment, or having received intravenous antibiotic therapy for an infection.
• Any other active or recent infection within 4 weeks prior to enrollment that, in the investigator's judgment, would pose an unacceptable risk to the patient.

Note: Recent viral upper respiratory tract infections or uncomplicated urinary tract infections should not be considered clinically significant.

• Patients with hepatic or renal insufficiency, gastrointestinal ulcer, active hepatitis, active rheumatic autoimmune disease, active tuberculosis, or poorly controlled psychiatric disorders.
• Cardiac, pulmonary, hepatic, renal, or coagulation dysfunction that, in the investigator's judgment, makes the patient unsuitable for enrollment.
• History of hypersensitivity to tocilizumab.
• Previous treatment with tocilizumab (a single prior dose may be exempted upon investigator's assessment).
• Any major surgery within 8 weeks prior to screening, or requirement for major surgery during the study period, which, in the investigator's judgment, would pose an unacceptable risk to the patient.
• Presence of the following laboratory abnormalities, or any other laboratory value outside the reference range deemed by the investigator to pose an unacceptable risk for participation:

• AST or ALT ≥ 2 × upper limit of normal (ULN)
• Alkaline phosphatase (ALP) ≥ 2 × ULN
• Total bilirubin (TBL) ≥ 1.5 × ULN
• Hemoglobin < 9.0 g/dL
• Total white blood cell count < 2.5 × 10⁹ cells/L
• Neutropenia (absolute neutrophil count [ANC] < 1.2 × 10⁹ cells/L)
• Lymphopenia (lymphocyte count < 0.75 × 10⁹ cells/L)
• Thrombocytopenia (platelets < 100 × 10⁹/L)
• Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m² (based on the CKD-EPI equation) Note: The above abnormalities may be retested during the screening period, with eligibility determined based on the retest results.
• Administration of a live or attenuated vaccine within 6 weeks prior to the first dose, or planned administration during the treatment period or within 6 weeks after the last dose.
• Body weight ≥ 100 kg.