Rituximab for the Treatment of Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract

Introduction Disease relapses are frequent in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We evaluated the outcomes of patients re-treated with rituximab (RTX) and prednisone for severe disease relapses. Methods The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rates of remission induction among patients treated with RTX (n = 99) and patients treated with cyclophosphamide (CYC) followed by azathioprine (AZA) (n = 98). Prednisone was tapered to discontinuation after 5.5 months. After achieving remission, patients who experienced a severe disease relapse between months 6 and 18 were eligible to receive RTX and prednisone on an open-label basis according to a pre-specified protocol. Investigators remained blinded to the original treatment assignment. Results Twenty-six patients received treatment with RTX for disease relapse after initially achieving remission on their originally assigned treatment. Fifteen patients were initially randomized to RTX and 11 to CYC/AZA. Thirteen (87%) of the patients originally assigned to RTX and 10 (91%) originally assigned to CYC/AZA achieved remission again with open-label RTX, an overall percentage of 88%. Half of the patients treated with open-label RTX were able to discontinue prednisone entirely. Patients in this cohort experienced fewer adverse events compared to the overall study population (4.7 adverse events/patient-year versus 11.8 adverse events/patient-year, respectively). Conclusion Re-treatment of AAV relapses with RTX and glucocorticoids appears to be a safe and effective strategy, regardless of previous treatment.

Refractory cutaneous polyarteritis nodosa with threat of loss of feet: successful treatment with rituximab

“…Considering the immediate threat of loss of digits, significant potential for loss of foot, and probable irreversibly compromised arterial supply to feet which future recurrences of CPAN would doi: 10.7243/2055-7000-4-1 exacerbate, we decided to infuse rituximab 1000 mg day 0 and day 15 with concomitant use of azathioprine 100mg and 60 mg prednisone daily. Rituximab has been shown to be effective in other types of vasculitides for induction and maintenance therapy [16][17][18].…”

Therapeutisches Vorgehen bei ANCA-assoziierten Vaskulitiden

“…Es konnte jedoch ein signifikanter Wirksamkeitsvorteil für RTX im Vergleich zu CYC nach 6 und 12 Monaten gezeigt werden, der aber mit nachlassender RTX-Wirkung nach 18 Monaten nicht mehr Bestand hatte [48]. Patienten, die im Verlauf der Studien erneut ein schweres Rezidiv entwickelten und prospektiv erneut RTX erhielten, sprachen ähnlich gut auf die Therapie an wie bei der Erstapplikation [35].…”

Tratamiento de la proteinosis alveolar primaria del adulto

“…Debido a la escasa evidencia en la que se basa el tratamiento y con el objetivo de ser más preciso al definir aquellos casos de PAP que requieren un tratamiento más específico, algunos autores proponen criterios más objetivos, basados fundamentalmente en las alteraciones que se producen en la oxigenación, de manera que serían candidatos a tratamiento aquellos casos que presentaran: Seymour et al 28 GM-CSF sc 5 mg/kg/día 10-26 semanas 36% (n = 14) Kavuru et al 39 GM-CSF sc 250 g/día hasta 5-9 g/kg/día 12 semanas 75% (n = 4) Bonfield et al 30 GM-CSF sc 250 g/día hasta 18 g/kg/día 12-48 semanas 55% (n = 11) Venkateshiah et al 31 GM-CSF sc 250 g/día hasta 5-18 g/kg/día 12-52 semanas 48% (n = 21) Tazawa et al 32 GM-CSF inh 250 g/día semanas alternas 24 semanas 100% (n = 3) Wylam et al 33 GM-CSF inh 250-500 g/día 12 semanas 83% (n = 12) Borie et al 34 Rituximab iv 1 g día 0 y 15 15 días 100% (n = 1) Amital et al 35 Rituximab iv 375 mg/m 2 semanal 4 semanas 100% (n = 1) Kavuru et al 36 Rituximab iv 1 g días 0 y 15 15 días 78% (n = 9) inh: vía inhalatoria; iv: vía intravenosa; sc: vía subcutánea. a) una PaO 2 en reposo < 65 mmHg; b) una diferencia alveoloarterial de O 2 ≥40 mmHg, y c) presencia de un shunt > 10-12% 21 .…”

“…Se han propuesto varios mecanismos de acción: citotoxicidad mediada por el complemento, citotoxicidad mediada por células dependiente de anticuerpos o incremento de la apoptosis mediada por anticuerpos. Rituximab se emplea en el tratamiento de enfermedades linfoproliferativas de linfocitos B y en varias enfermedades autoinmunes, como lupus eritematoso sistémico, artritis reumatoide o vasculitis 35 . Dado que la PAP primaria es considerada una enfermedad autoinmune en la que participan anticuerpos frente al GM-CSF, la reducción de los linfocitos B y los niveles de anti GM-CSF que produciría rituximab podría ser una opción eficaz para el tratamiento 36 .…”