Study of Salvage Therapy to Treat Patients with Granulomatosis with Polyangiitis

Exclusion Criteria

• •An allergy or hypersensitivity to monoclonal antibodies or either of the study drugs (rituximab, abatacept or tocilizumab) or to their excipients
• •A previous treatment with a combination of rituximab plus a cDMARD, with tofacitinib, or with tocilizumab
• •A contraindication to a combination of rituximab plus a cDMARD, to tofacitinib, or to tocilizumab (including an ongoing infection; history of recent cancer \<5 years before enrollment, except for cured non-melanoma skin cancer); pregnancy; and breastfeeding.
• •Patients with severe vasculitis manifestations that requires plasma exchange therapy including severe renal failure with a creatinine level ≥350 µmol/L or severe alveolar haemorrhage
• •Patients with vasculitis in remission
• •Patients with symptoms attributable to chronic and non-active GPA
• •Patients with severe cardiac failure defined as class IV in New York Heart Association
• •Patients with acute infections or chronic active infections (including HIV, HBV or HCV)
• •Patients with active cancer or recent cancer (\<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment
• •Pregnant women and lactation. All women with childbearing potential are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception from the date of consent through the end of the study, and for women who are taking tocilizumab or tofacitinib through 3 months after the last treatment administration, for women who are taking rituximab in combination with methotrexate through 6 months after the last treatment administration, for women who are taking rituximab in combination with mycofenolate mofetil or with azathioprine through 3 months after the last treatment administration
• •Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol
• •Patients included in other investigational therapeutic study within the previous 3 months
• •Patients suspected not to be observant to the proposed treatments
• •Laboratory parameter exclusions
• •1. aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) \> 5 times upper limit of normal
• •2. Platelet count \<100.000/mm3
• •3. White blood cell count \<2000/mm3