Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis

Published:October 26, 2021DOI:https://doi.org/10.1016/j.ejim.2021.10.028

      Highlights

      • In GPA, relapses remain frequent and refractory manifestations may occur.
      • Off-label use of TNF-α blockers shows efficacy in less than 50% of refractory and/or relapsing GPA.
      • Off-label use of abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

      Abstract

      Objective

      To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA).

      Methods

      We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens.

      Results

      Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3–6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3–8) and 2 (1–6), and 20 (13–30) mg/day and 20 (15–25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6–13) and 11 months (IQR 6–18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection.

      Conclusion

      This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

      Graphical abstract

      Keywords

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      References

        • Jennette J.C.
        • Falk R.J.
        • Bacon P.A.
        • Basu N.
        • Cid M.C.
        • Ferrario F.
        • et al.
        2012 revised international Chapel Hill consensus conference nomenclature of Vasculitides.
        Arthritis Rheum. 2013; 65 (Jan): 1-11
        • Yates M.
        • Watts R.A.
        • Bajema I.M.
        • Cid M.C.
        • Crestani B.
        • Hauser T.
        • et al.
        EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.
        Ann Rheum Dis. 2016; 75 (Sep): 1583-1594
        • Terrier B.
        • Darbon R.
        • Durel C.-.A.
        • Hachulla E.
        • Karras A.
        • Maillard H.
        • et al.
        French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides).
        Orphanet J Rare Dis. 2020; 15 (Dec 29): 351
        • Mukhtyar C.
        • Flossmann O.
        • Hellmich B.
        • Bacon P.
        • Cid M.
        • Cohen-Tervaert J.W.
        • et al.
        Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.
        Ann Rheum Dis. 2008; 67 (Jul): 1004-1010
        • Guardiani E.
        • Moghaddas H.S.
        • Lesser J.
        • Resta-Flarer F.
        • Blitzer A.
        • Bhora F.
        • et al.
        Multilevel airway stenosis in patients with granulomatosis with polyangiitis (Wegener’s).
        Am J Otolaryngol. 2015; 36 (Jun): 361-363
        • Lutalo P.M.K.,.D.
        • Cruz DP.
        Biological drugs in ANCA-associated vasculitis.
        Int Immunopharmacol. 2015; 27 (Aug): 209-212
        • Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group
        Etanercept plus standard therapy for Wegener’s granulomatosis.
        N Engl J Med. 2005; 352 (Jan 27): 351-361
        • Laurino S.
        • Chaudhry A.
        • Booth A.
        • Conte G.
        • Jayne D.
        Prospective study of TNFalpha blockade with adalimumab in ANCA-associated systemic vasculitis with renal involvement.
        Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2010; 25 (Oct): 3307-3314
        • Langford C.A.
        • Monach P.A.
        • Specks U.
        • Seo P.
        • Cuthbertson D.
        • McAlear C.A.
        • et al.
        An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s).
        Ann Rheum Dis. 2014; 73 (Jul): 1376-1379
        • Stone J.H.
        • Merkel P.A.
        • Spiera R.
        • Seo P.
        • Langford C.A.
        • Hoffman G.S.
        • et al.
        Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
        N Engl J Med. 2010; 363 (Jul 15): 221-232
        • Jones R.B.
        • Cohen Tervaert J.W.
        • Hauser T.
        • Luqmani R.
        • Morgan M.D.
        • Peh C.A.
        • et al.
        Rituximab versus Cyclophosphamide in ANCA-Associated Renal Vasculitis.
        N Engl J Med. 2010; 363 (Jul 15): 211-220
        • Guillevin L.
        • Pagnoux C.
        • Karras A.
        • Khouatra C.
        • Aumaître O.
        • Cohen P.
        • et al.
        Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis.
        N Engl J Med. 2014; 371 (Nov 6): 1771-1780
        • Gopaluni S.
        • Smith R.M.
        • Lewin M.
        • McAlear C.A.
        • Mynard K.
        • Jones R.B.
        • et al.
        Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial.
        Trials. 2017; 18 (Mar 7): 112