Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations

Aries, Peer; Hellmich, Bernhard; Voswinkel, Jan; Both, Marcus; Nölle, Bernhard; Holl‐Ulrich, Konstanze; Lamprecht, Peter; Gross, Wolfgang L.

doi:10.1136/ard.2005.044420

Cited by 182 publications

(120 citation statements)

References 22 publications

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“…This patient had a long disease course and was exposed to a high cumulative dose of CYC. Aries et al (28) reported improvement in only 3 of their 8 patients who had disease manifestations and chronicity similar to those in our patient. On the other hand, our results show that rituximab is effective therapy for granulomatous manifestations, such as retroorbital granuloma and endobronchial disease, in the majority of patients.…”

Section: Discussionsupporting

confidence: 86%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

323

214

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Objective. B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as retreatment biomarkers.Methods. Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.Results. All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P ‫؍‬ 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m 2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of lateonset neutropenia, which were attributed to rituximab.Conclusion. Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.

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Section: Discussionsupporting

confidence: 86%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

323

214

View full text Add to dashboard Cite

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“…Successful effectiveness with Rituximab has been reported on three patients with scleritis and peripherative ulcerative keratitis associated with Wegener's granulomatosis [18,[20][21][22][23]. Another case of peripherative ulcerative keratitis associated to Wegener's granulomatosis completely resolved with two Rituximab infusions, given according to the protocol of 1000 mg/infusion at two weeks apart [24].…”

Section: Scleritis and Orbital Inflammationmentioning

confidence: 99%

“…Rituximab has been successfully used for the treatment of refractory keratoconjunctivitis, scleritis [18][19][20][21][22][23], peripheral ulcerative keratitis [24,25], uveitis [26][27][28][29] and ocular surface inflammatory diseases such as cicatricial pemphigoid [30,31] also when associated with systemic diseases. Experience in inflammatory ocular diseases is still scarce with few case reports on its efficacy.…”

Section: Rituximab In Inflammatory Eye Diseasesmentioning

confidence: 99%

“…Another case of peripherative ulcerative keratitis associated to Wegener's granulomatosis completely resolved with two Rituximab infusions, given according to the protocol of 1000 mg/infusion at two weeks apart [24]. Some authors showed limited evidence that scleritis and orbital inflammation may respond to Rituximab, probably due to the presence of fibrotic nature of granulomas in Wegener's, especially when occurring retroorbital [22]. Taylor and colleagues reported clinical improvement in 10 patients with refractory granulomatous ocular Wegener's mainly scleritis and orbital granulomas [21].…”

Section: Scleritis and Orbital Inflammationmentioning

confidence: 99%

“…All patients were ANA positive and negative for RF and HLA-B27 antigens. The mean age at onset of arthritis was 2.8 ± 2.4 (SD) years (range 1-8), while the mean age at onset of uveitis was 4.1 ± 3.9 (SD) years (range 1-12); the mean ocular disease duration was 16.12 years (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and the mean duration of arthritis was 17.35 years (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. In six out of eight patients the ocular involvement was bilateral (total number of treated eyes : 14).…”

Section: Children With Juvenile Idiopathic Arthritis Associated Uveitmentioning

confidence: 99%

See 2 more Smart Citations

Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

Miserocchi¹,

Pontikaki

Modorati³

et al. 2011

Autoimmunity Reviews

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Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

Lally

Lebovics

Huang

et al. 2014

Arthritis Care & Research

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Objective. Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegener's) (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GPA, none have evaluated its efficacy solely for ENT manifestations. We compared the effectiveness of RTX to other therapies for the ENT manifestations of GPA in a large, well-characterized cohort. Methods. We performed a retrospective analysis of 975 visits from 99 GPA patients seen at a tertiary care ENT practice between 2003 and 2013. At each visit, subjects had a complete ENT examination, with ENT activity assessed by a single expert otolaryngologist. ENT disease activity during the observational period in subjects receiving RTX was compared to subjects receiving all other therapy. Results. In total, 48 subjects had never received RTX and 51 received RTX at least once. There was no active ENT disease during 92.4% of the observational period (days) for subjects receiving RTX, compared with 53.7% of the observational period for subjects not receiving RTX (odds ratio 11.0 [95% confidence interval 5.5-22.0], P < 0.0001). Subjects receiving RTX, compared with those receiving methotrexate, azathioprine, cyclophosphamide, or trimethoprim-sulfamethoxazole, were significantly more likely to have no active ENT disease (P < 0.0001 for each comparison). Conclusion. RTX is an effective treatment for ENT manifestations of GPA. Subjects treated with RTX were significantly less likely to have active ENT disease compared with those not receiving RTX. Patients being treated with RTX were 11 times less likely to have active ENT disease than patients being treated with other therapies.

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Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations

Cited by 182 publications

References 22 publications

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

Effectiveness of Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis (Wegener's)

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