Experience with effective combined anti-B-cell therapy with rituximab and belimumab for refractory granulomatosis with polyangiitis (Wegener's) with severe lung damage

Systemic vasculitis (SV) associated with antineutrophil cytoplasmic antibodies (ANCA) is characterized by severe multiple organ lesions with a poor prognosis. The successful introduction of standard therapy with cyclophosphamide (CP) and innovative anti-B-cell therapy with rituximab (RTM) for the treatment of ANCA SV gives no grounds to stop further searching for effective and safe therapy since about 10-15% of patients with ANCA SV are refractory to standard therapy with CP; after the latter, approximately 40% of patients develop recurrences, and granulomatous inflammation in the respiratory organs in granulomatosis with polyangiitis (GPA) can be resistant to RTM treatment, especially following its single cycle. There is increasing evidence that the efficiency of anti-B-cell therapy can be enhanced by adding belimumab (BLM). The paper describes a clinical case of effective sequential combined anti-B-cell therapy with BLM and RTM for remission induction in a female patient who has GPA with severe granulomatous lung injury refractory to previous therapy with CP (a total dose of 6.2 g) and a single cycle of therapy with RTM (a total dose of 2.6 g). BLM was used 12 months after RTM administration because there were no positive changes in lung injury. At 12 months after initiations of treatment with BLM (800 mg twice at a weekly interval, then 800 mg monthly), there was a substantial reduction in the lung parenchymal foci, as evidenced by multislice spiral computed tomography (MSCT); and the treatment was continued for another 6 months, thereafter discontinued due to the occurrence of ulcerative stomatitis. After its relief, RTM was again given at reduced dose cycles of 500 mg every 6 months; lung MSCT showed further improvement and remission achieved. BLM may be effective in treating the GPA patients who are refractory to CP and have an insufficient response to RMT treatment. Combined anti-B-cell therapy aimed at depleting SD20+ B-cells and at blocking BAFF may be a promising area for the treatment of patients with ANCA SV.