Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations

Holle, Julia; Dubrau, Christin; Herlyn, Karen; Heller, Martin; Ambrosch, Petra; Noelle, Bernhard; Reinhold‐Keller, E.; Gross, Wolfgang L.

doi:10.1136/ard.2011.153601

Cited by 166 publications

(98 citation statements)

References 30 publications

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“…10 R-CHOP (rituximab ϩ cyclophosphamide ϩ hydroxydaunorubicin ϩ vincristine ϩ prednisone/prednisolone) is the most widely used for these types of lymphoma. Moreover, the usefulness of rituximab has also been demonstrated in patients with certain refractory autoimmune diseases, including rheumatoid arthritis, 11 granulomatosis with polyangitis, 12 and antineutrophil cytoplasmic antibody-associated vasculitis. 13 The great success of rituximab is being followed by the development of new monoclonal antibodies to CD20.…”

Section: Introductionmentioning

confidence: 99%

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Kusumoto

Tobinai

2014

Hematology

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Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody-rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab ϩ cyclophosphamide ϩ hydroxydaunorubicin ϩ vincristine ϩ prednisone/prednisolone)-is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%-80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%-24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection. Learning Objectives• To become familiar with the risk of HBV reactivation in patients who receive anti-B-cell therapy • To manage such high-risk patients successfully using antiviral prophylaxis or by HBV DNA-monitoring-guided preemptive antiviral therapy

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Section: Introductionmentioning

confidence: 99%

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Kusumoto

Tobinai

2014

Hematology

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“…Again, all patients in this study were refractory to multiple other therapies, and there was no comparison group of similar patients who did not receive RTX. Holle and colleagues compared the efficacy of RTX in refractory GPA patients with vasculitic versus granulomatous manifestations and included 9 patients with limited ENT disease in their cohort of 59 patients (14). The authors concluded that most of the failure to respond to RTX was due to limited efficacy in granulomatous disease; however, this result was again largely driven by lack of response of orbital masses and pachymeningitis.…”

Section: Discussionmentioning

confidence: 99%

“…There have been a few small studies examining the use of RTX for granulomatous manifestations of GPA (11)(12)(13)(14). These small case series classified all granulomatous manifestations together and reported variable outcomes regarding the effectiveness of RTX for granulomatous GPA.…”

Section: Introductionmentioning

confidence: 99%

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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“…Half of the patients have chronic renal disease [13,14]. Half of the patients receive RTX in monotherapy [13,14] while the others receive RTX in combination with other immunosuppressive drugs [29,31].…”

Section: Discussionmentioning

confidence: 99%

“…At least 6 AAV patients (1.2%) treated with RTX developed PCP among 516 patients from different cohorts [9][10][11][12][13][14][29][30][31][32] and proved fatal in 2 patients. PCP occurred 2, 3 and 32 months after the last RTX infusion in 3 patients including ours [13,29]. Half of the patients have chronic renal disease [13,14].…”

Section: Discussionmentioning

confidence: 99%

Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones’s Locker?

Besada

Nikolaissen

Nossent

2012

Scandinavian Journal of Rheumatology

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Reports in haematology, transplantation medicine and rheumatology indicate that Rituximab, a B cell depleting therapy, increases the risk for Pneumocystis jiroveci pneumopathy. Patients with ANCA-associated vasculitis have an increased incidence of Pneumocystis jiroveci pneumopathy compared to other autoimmune diseases and Rituximab is often used to induce and maintain remission.Herein we present a case of a patient with granulomatosis with polyangiitis treated with Rituximab for relapse that developed Pneumocystis jiroveci pneumopathy 3 months after and we review the relevant literature to assess Pneumocystis jiroveci pneumopathy incidence and risks factors under Rituximab. We also discuss whether pneumocystis jiroveci screening before Rituximab and Pneumocystis jiroveci pneumopathy prophylaxis under Rituximab are indicated.Pneumocystis jiroveci colonization is found in 25% of patients with autoimmune diseases. However the association between colonization and Pneumocystis jiroveci pneumopathy development is not very strong.Pneumocystis jiroveci pneumopathy incidence in ANCA-associated vasculitis patients treated with Rituximab is found to be 1.2%. Therefore evidence and practice do not support the use of Pneumocystis jiroveci pneumopathy chemoprophylaxis in all ANCA-associated vasculitis patients receiving Rituximab. CD4 cell count cut-off does not work well in patients treated with Rituximab as it does not reflect T-cell impairment following B cell depletion.To help stratify the risk of both colonization and Pneumocystis jiroveci pneumopathy development, assessment of the patient's net stat of immunodeficiency before administering Rituximab -including age, renal or lung involvement, previous infections due to T cell dysfunction, blood tests (lymphocytopenia, low CD4 cell count) and concomitant therapy -is warranted.

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Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations

Cited by 166 publications

References 30 publications

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

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

Should rheumatoid factor in rheumatoid arthritis be sent to Davy Jones’s Locker?

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