Background Anti-CD20 antibody rituximab (RTX) has proved beneficial in ANCA-associated vasculitis (AAV). However, granulomatous features typical for the granulomatosis with polyangiitis (GPA) can be resistant to RTX, primarily after a single course. Local production of B-cell activating factor (BAFF) in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies. The anti-BAFF monoclonal antibody (belimumab) has shown efficacy in SLE, and its role as a relapse prevention agent in AAV is being assessed in a randomized trial (BREVAS), but whether BAFF-neutralization can be used to induce remission of AAV remains unsolved.

There is some evidence for increasing of BAFF levels after RTX treatment (Holden et al., 2011) and high levels of BAFF are associated with a shorter duration of the RTX-induced B-cell depletion. Thus, addition of belimumab should potentially enhance B-cell suppression.

Objectives Here we present the first clinical case report of effective belimumab use for remission induction in GPA with severe pulmonary granulomatous inflammation, which was refractory to cyclophosphamide (CYC) and one course of RTX.

Results A 56-year-old woman with 6-month history of fever, rhinitis, otitis, cough, polyarthralgia and cranial nerve affection was admitted to hospital. A chest X-ray revealed bilateral nodules. Fiberoptic bronchoscopy revealed infiltration in the subglottic area and ulcerated lesions along the tracheobronchial tree. She also had elevated inflammatory markers (ESR 24 mm/h, CRP 48 mg/dL), thrombocytosis (PLT 781×10³/mm³) and cytoplasmatic pattern positive ANCA by indirect immunofluorescence screening. GPA was diagnosed. Induction therapy included prednisolone (40 mg/day) and pulses of CYC and methylprednisolone.

6 mo later CYC total dose (TD) was 6.2 g, prednisolone 15 mg/day. A CT scan revealed new focuses of granulomatous inflammation in lungs. Birmingham Vasculitis Activity Score (BVAS)=8. ESR 45 mm/h, CRP 13 mg/dL, platelets 323×10³/mm³, ANCA was negative. RTX (TD 2.6 g) was administered due to the refractory GPA and resulted in B-cell depletion.

After 6 mo of RTX clinical improvement was achieved, however, a CT scan revealed persistence of pulmonary lesions (A). BVAS=6. CRP 2 mg/dL, CD19+ B-cells 0%. Mycophenolate mofetil 1 g/day was initiated but soon discontinued due to nausea and replaced by azathioprine 100 mg/day. As there was no significant improvement after 12 mo of RTX (B), treatment with belimumab was initiated (800 mg/wk N2, then 800 mg/mo).

CT monitoring showed consistent improvement of pulmonary lesions after administration of belimumab (C), but at 12 mo the lesions failed to resolve completely, necessitating the prolongation of Belimumab to total 18 mo, then due to poor tolerability (emerging stomatitis) it had to be discontinued. Thus, RTX was restarted at 500 mg twice with 6 mo interval, providing further improvement in CT images.

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Conclusions Belimumab can be useful in treatment of patients with GPA, who are refractory to CYC and RTX. Combined approach to B-cell targeting with both anti-CD20 and anti-BAFF treatment can represent promising strategy for patients with severe refractory GPA.

1. Holden NJ, Williams JM, Morgan MD, et al. ANCA-stimulated neutrophils release BLyS and promote B-cell survival: a clinically relevant cellular process. Ann Rheum Dis. 2011; 70(12):2229–33.

Disclosure of Interest None declared