Otolaryngological progression of granulomatosis with polyangiitis after systemic treatment with rituximab.

doi:10.1177/0194599813509784

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Otolaryngological progression of granulomatosis with polyangiitis after systemic treatment with rituximab.

Journal Article•DOI•

Otolaryngological progression of granulomatosis with polyangiitis after systemic treatment with rituximab.

Ian-James Malm¹, David J. Mener¹, Jean Kim¹, Philip Seo¹, Young J. Kim¹ - Show less +1 more•Institutions (1)

Johns Hopkins University¹

01 Jan 2014-Otolaryngology-Head and Neck Surgery (SAGE Publications)-Vol. 150, Iss: 1, pp 68-72

TL;DR: While rituximab has been shown to be noninferior to cyclophosphamide with respect to remission from systemic GPA, these patients continue to have chronic otolaryngological manifestations of their disease and must continue to play a supportive role throughout their maintenance period.

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Abstract: ObjectiveRituximab is used for the treatment of granulomatosis with polyangiitis (GPA), historically known as Wegener’s granulomatosis. However, the otolaryngological progression of GPA after systemic treatment with rituximab (Rituxan) is unclear. We therefore examined the disease sequelae of patients with GPA who were treated with rituximab.Study DesignCase series with chart review.SettingTertiary care medical center.Subjects and MethodsPatients with a diagnosis of GPA who were treated with rituximab between 2006 and 2012 were included in this study. Systemic and otolaryngological symptomatology, prednisone usage, and procedural interventions following B-cell depletion were analyzed.ResultsWe identified 11 patients who met our inclusion criteria. The average length of follow-up after treatment with rituximab was 23.5 months. After treatment with rituximab, there was a significant decrease in daily prednisone dose at 3, 12, and 18 months postinfusion (P < .05). However, there was no observed improvement i...

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Journal Article•DOI•

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

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Wytske Fokkens¹, Valerie J. Lund, Joachim Mullol, Claus Bachert², Isam Alobid, Fuad M. Baroody³, Noam A. Cohen⁴, Anders Cervin⁵, Richard Douglas⁶, Philippe Gevaert², Christos Georgalas¹, Herman Goossens⁷, Richard J. Harvey⁸, Peter Hellings⁹, Claire Hopkins¹⁰, Nick Jones¹¹, Guy Joos², Livije Kalogjera¹², Bob Kern¹³, Marek L. Kowalski¹⁴, David Price¹⁵, Herbert Riechelmann, Rodney J. Schlosser¹⁶, Brent A. Senior¹⁷, Mike Thomas¹⁸, Elina Toskala⁴, Richard Louis Voegels¹⁹, De Yun Wang²⁰, Peter-John Wormald²¹ - Show less +25 more•Institutions (21)

University of Amsterdam¹, Ghent University², University of Chicago³, University of Pennsylvania⁴, Lund University⁵, Auckland City Hospital⁶, University of Antwerp⁷, University of New South Wales⁸, Katholieke Universiteit Leuven⁹, Guy's and St Thomas' NHS Foundation Trust¹⁰, Queen's University¹¹, University of Zagreb¹², Northwestern University¹³, Medical University of Łódź¹⁴, University of Aberdeen¹⁵, Medical University of South Carolina¹⁶, University of North Carolina at Chapel Hill¹⁷, University of Southampton¹⁸, University of São Paulo¹⁹, National University of Singapore²⁰, Flinders University²¹

20 Feb 2020-Rhinology

TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012 and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery.

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Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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2,853 citations

Journal Article•DOI•

Rituximab for induction and maintenance therapy in granulomatosis with polyangiitis (Wegener's). Results of a single-center cohort study on 66 patients.

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Ana Luisa Calich¹, Xavier Puéchal², Xavier Puéchal³, Grégory Pugnet², Jonathan London², Benjamin Terrier², Pierre Charles², Luc Mouthon², Loïc Guillevin² - Show less +5 more•Institutions (3)

University of São Paulo¹, Paris Descartes University², French Institute of Health and Medical Research³

01 May 2014-Journal of Autoimmunity

TL;DR: It is concluded that in this single-center cohort, RTX associated with glucocorticoid treatment adapted for disease severity appeared to induce remission effectively in GPA patients, and maintenance treatment with low doses of RTX in a routine time-based protocol was safe and associated with low rates of relapse on treatment.

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71 citations

Journal Article•DOI•

Granulomatosis With Polyangiitis in Otolaryngologist Practice: A Review of Current Knowledge.

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Joanna Wojciechowska, Wojciech Krajewski¹, Piotr K. Krajewski¹, Tomasz Kręcicki•Institutions (1)

Wrocław Medical University¹

07 Mar 2016-Clinical and Experimental Otorhinolaryngology

TL;DR: In clinical practice diagnosis, the presence of distinctive ANCA antibodies and biopsy of affected organ are crucial, and GPA must be differentiated from neoplastic, infectious or inflammatory ulcerative lesions of the head and neck.

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Abstract: Granulomatosis with polyangiitis (GPA) is an idiopathic vasculitis of medium and small arteries, characterized by necrotizing granulomatous inflammation. GPA typically affects upper and lower respiratory tract with coexisting glomerulonephritis. This disease is generally characterized by antineutrophil cytoplasm antibodies (ANCA), nevertheless, there are rare cases with negative ANCA. GPA affects people at any age, with predominance of the sixth and seventh decade of life. In 80%-95% of the patients the first symptoms of GPA are otorhinolaryngological manifestations of head and neck including nose/sinuses, ears, eyes, larynx/trachea, oral cavity, and salivary glands. Diagnosis of GPA is based on Criteria of the American College of Rheumatology. In clinical practice diagnosis, the presence of distinctive ANCA antibodies and biopsy of affected organ are crucial. GPA must be differentiated from neoplastic, infectious or inflammatory ulcerative lesions of the head and neck. The standard treatment procedure is divided into two essential phases, induction and maintenance. The induction phase is based on combination of systemic corticosteroid and immunosuppressant therapy, whereas the maintenance phase comprises corticosteroids and azathioprine/methotrexate supplementation. Surgical treatment ought to be considered for patients who are not responding to pharmacotherapy.

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50 citations

Cites background from "Otolaryngological progression of gr..."

...Results of RTX use in otolaryngology are generally good, however, there are available studies showing GPA otolaryngological manifestations endurance after RTX therapy [18,35]....
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Journal Article•DOI•

Clinical aspects of granulomatosis with polyangiitis affecting the head and neck

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Andreas Knopf¹, Adam Chaker¹, Thomas Stark¹, Benedikt Hofauer¹, Tobias Lahmer¹, Klaus Thürmel¹, Murat Bas¹ - Show less +3 more•Institutions (1)

Technische Universität München¹

01 Jan 2015-European Archives of Oto-rhino-laryngology

TL;DR: Early and sufficient systemic therapy for all HN-GPA patients is suggested and Nasal mucosal “blind” biopsy should be performed in patients with elevated auto-antibodies but lacking clinical head and neck manifestations.

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Abstract: There are many controversies in head and neck granulomatosis with polyangiitis (HN-GPA). Diagnostic/therapeutic regimens vary due to limited knowledge about the special properties of HN-GPA. 28 patients were diagnosed with GPA accordingly. Anti-neutrophil-cytoplasmatic-antibody (ANCA), anti-peroxidase-antibody (anti-PR3) and biopsies were performed for all patients and set into clinical context. 14 patients had sinonasal symptoms. Otological (n = 8) and laryngeal (n = 2) symptoms were usually associated with complex disease activity. Pulmonary and/or renal impairment was present in 14 patients at the time of diagnosis and developed in a further nine patients within 1 year. 21 patients with systemic disease displayed elevated ANCA/anti-PR3. In contrast, those with persistent isolated HN manifestations (n = 6) lacked auto-antibodies. These patients underwent multiple biopsies to diagnose GPA. Interestingly, five patients without clinical HN manifestations but elevated auto-antibodies were identified by nasal “blind” biopsy. Clinical examination, auto-antibody testing, and histology are effective diagnostic tools in HN-GPA. Histological diagnosis remains the gold standard in patients with persistent isolated head and neck manifestations but missing auto-antibodies. Based on our findings, we suggest early and sufficient systemic therapy for all HN-GPA. Nasal mucosal “blind” biopsy should be performed in patients with elevated auto-antibodies but lacking clinical head and neck manifestations.

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14 citations

Cites background from "Otolaryngological progression of gr..."

...While there is proven evidence of the beneficial application of rituximab in systemic disease, the therapeutic impact in the head and neck remains unclear [24, 25]....
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Journal Article•DOI•

Estenosis subglótica y granulomatosis con poliangeítis (Wegener) en dos casos: Report of two cases

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María Massa, Nicholas C Emery, Martín Bosio, Bárbara C Finn, Julio E Bruetman, Pablo Young - Show less +2 more

01 Mar 2014-Revista Medica De Chile

TL;DR: It is reported that two females aged 40 and 52 years, admitted to the hospital with a subglottic tracheal stenosis, responded to rituximab and required a tracheostomy.

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Abstract: Granulomatosis with polyangiitis (GPA) or Wegener's disease is characterized by a granulomatous vasculitis of the upper and lower airways and kidney. It involves the lower respiratory tract causing subglottic tracheal stenosis, which occurs in approximately 22% of patients. We report two females aged 40 and 52 years, admitted to the hospital with a subglottic tracheal stenosis. Their symptoms and management are reviewed. The frst patient responded to rituximab. The second patient required a tracheostomy.

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8 citations

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Journal Article•DOI•

Wegener granulomatosis : an analysis of 158 patients

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Gary S. Hoffman¹, Gail S. Kerr¹, Randi Y. Leavitt¹, Claire W. Hallahan¹, Robert S. Lebovics¹, William D. Travis¹, Menachem Rottem¹, Anthony S. Fauci¹ - Show less +4 more•Institutions (1)

National Institutes of Health¹

15 Mar 1992-Annals of Internal Medicine

TL;DR: The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids, and has led to increasing concerns about toxicity resulting from prolonged cycloph phosphamide therapy and has encouraged investigation of other therapeutic regimens.

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Abstract: Objective To prospectively study the clinical features, pathophysiology, treatment and prognosis of Wegener granulomatosis. Design Of the 180 patients with Wegener granulomatosis referred to the National Institute of Allergy and Infectious Diseases during the past 24 years, 158 have been followed for 6 months to 24 years (a total of 1229 patient-years). Measurements Characteristics of clinical presentation, surgical pathology, course of illness, laboratory and radiographic findings, and the results of medical and surgical treatment have been recorded in a computer-based information retrieval system. Setting The Warren Magnuson Clinical Center of the National Institutes of Health. Main results Men and women were equally represented; 97% of patients were white, and 85% were more than 19 years of age. The mean period of follow-up was 8 years. One hundred and thirty-three patients (84%) received "standard" therapy with daily low-dose cyclophosphamide and glucocorticoids. Eight (5.0%) received only low-dose cyclophosphamide. Six (4.0%) never received cyclophosphamide and were treated with other cytotoxic agents and glucocorticoids. Ten patients (6.0%) were treated with only glucocorticoids. Ninety-one percent of patients experienced marked improvement, and 75% achieved complete remission. Fifty percent of remissions were associated with one or more relapses. Of 99 patients followed for greater than 5 years, 44% had remissions of greater than 5 years duration. Thirteen percent of patients died of Wegener granulomatosis, treatment-related causes, or both. Almost all patients had serious morbidity from irreversible features of their disease (86%) or side effects of treatment (42%). Conclusions The course of Wegener granulomatosis has been dramatically improved by daily treatment with cyclophosphamide and glucocorticoids. Nonetheless, disease- and treatment-related morbidity is often profound. Alternative forms of therapy have not yet achieved the high rates of remission induction and successful maintenance that have been reported with daily cyclophosphamide treatment. Despite continued therapeutic success with cyclophosphamide, our long-term follow-up of patients with Wegener granulomatosis has led to increasing concerns about toxicity resulting from prolonged cyclophosphamide therapy and has encouraged investigation of other therapeutic regimens.

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2,637 citations

"Otolaryngological progression of gr..." refers background in this paper

...Subglottic stenosis is also an important sequela of GPA, found in up to 16% to 23% of patients, and often requires multiple operative dilations.(4,5) Furthermore, chronic serous otitis media secondary to eustachian tube dysfunction and sensorineural hearing loss are both frequently observed in patients with GPA....
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Journal Article•DOI•

Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis

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John H. Stone¹, Peter A. Merkel², Robert Spiera³, Philip Seo⁴, Carol A. Langford⁵, Gary S. Hoffman⁵, Cees G. M. Kallenberg⁶, E. William St. Clair⁷, Anthony M. Turkiewicz⁸, Nadia K. Tchao, Lisa Webber⁹, Linna Ding⁹, Lourdes P. Sejismundo⁴, Kathleen Mieras¹⁰, David Weitzenkamp, David Ikle, Vicki Seyfert-Margolis¹¹, Mark Mueller, Paul Brunetta¹², Nancy B. Allen⁷, Fernando C. Fervenza¹⁰, Duvuru Geetha⁴, Karina A. Keogh¹⁰, Eugene Y. Kissin², Paul A. Monach², Tobias Peikert¹⁰, Coen A. Stegeman⁶, Steven R. Ytterberg¹⁰, Ulrich Specks¹⁰ - Show less +25 more•Institutions (12)

Harvard University¹, Boston University², Hospital for Special Surgery³, Johns Hopkins University⁴, Cleveland Clinic⁵, University of Groningen⁶, Duke University⁷, University of Alabama at Birmingham⁸, National Institutes of Health⁹, Mayo Clinic¹⁰, Food and Drug Administration¹¹, Genentech¹²

15 Jul 2010-The New England Journal of Medicine

TL;DR: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease.

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Abstract: Background Cyclophosphamide and glucocorticoids have been the cornerstone of remissioninduction therapy for severe antineutrophil cytoplasmic antibody (ANCA)−associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. Methods We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Results Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. Conclusions Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

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2,100 citations

Journal Article•DOI•

Efficacy of Remission-Induction Regimens for ANCA-associated Vasculitis

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Ulrich Specks¹, Peter A. Merkel², Philip Seo³, Robert Spiera⁴, Carol A. Langford⁵, Gary S. Hoffman⁵, Cees G. M. Kallenberg⁶, E. William St. Clair⁷, Barri J. Fessler⁸, Linna Ding⁹, Lisa Viviano⁹, Nadia K. Tchao, Deborah Phippard, Adam Asare, Noha Lim, David Ikle, Brett Jepson, Paul Brunetta¹⁰, Nancy B. Allen⁷, Fernando C. Fervenza¹, Duvuru Geetha³, Karina A. Keogh¹, Eugene Y. Kissin², Paul A. Monach², Tobias Peikert¹, Coen A. Stegeman⁶, Steven R. Ytterberg¹, Mark Mueller⁹, Lourdes P. Sejismundo³, Kathleen Mieras¹, John H. Stone¹¹ - Show less +27 more•Institutions (11)

Mayo Clinic¹, Boston University², Johns Hopkins University³, Hospital for Special Surgery⁴, Cleveland Clinic⁵, University of Groningen⁶, Duke University⁷, University of Alabama at Birmingham⁸, National Institutes of Health⁹, Genentech¹⁰, Harvard University¹¹

31 Jul 2013-The New England Journal of Medicine

TL;DR: In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months.

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Abstract: A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide– azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the com parison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the Na tional Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)

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573 citations

"Otolaryngological progression of gr..." refers background in this paper

...Subglottic stenosis is also an important sequela of GPA, found in up to 16% to 23% of patients, and often requires multiple operative dilations.4,5 Furthermore, chronic serous otitis media secondary to eustachian tube dysfunction and sensorineural hearing loss are both frequently observed in patients with GPA.2 Otolaryngologists, therefore, play an integral role in the management and surveillance of patients with GPA....
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...rituximab, and in some cases as maintenance therapy, for patients who are unresponsive or with contraindications to classic treatments such as cyclophosphamide and methotrexate.(8) There is, however, a paucity of data regarding the clinical course of patients treated with rituximab from the otolaryngologist’s standpoint....
[...]
...Wegener’s granulomatosis, granulomatosis with polyangiitis, rituximab G ranulomatosis with polyangiitis (GPA), historically known as Wegener’s granulomatosis, is a systemic vasculitis that affects small and medium vessels predominately in the kidneys, lungs, and the mucosa of the upper respiratory tract.1 This ANCA (antineutrophil cytoplasmic antibody)–associated disease is characterized by the histological presence of granulomatosis, vasculitis, and necrosis.2 The reported prevalence of GPA in the United States is 3 per 100,000 people, predominately in whites, with an equal sex distribution and is, on average, diagnosed in the fifth decade of life.3-5 Otolaryngological manifestations of the disease have been well documented in the literature and are found in up to 90% of patients with GPA.4-6 Granulomatosis with polyangiitis most commonly affects the sinus and nasal mucosa, which leads to epistaxis, chronic sinusitis, and rhinosinusitis....
[...]
...Since then, several case-controlled cohorts and randomized controls trials have demonstrated the efficacy of rituximab for systemic GPA.7,8,11,12,14 The efficacy of rituximab for otolaryngological manifestation of the disease, however, has been more equivocal....
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...Despite this, our analysis is important in that it highlights the limitations of rituximab to fully control otolaryngological manifestations of GPA....
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Journal Article•DOI•

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis

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Bernhard Hellmich, Oliver Flossmann, Wolfgang L. Gross, Paul A. Bacon¹, Jan Willem Cohen-Tervaert², Loïc Guillevin³, David Jayne, Alfred Mahr³, Peter A. Merkel⁴, Heiner Raspe, David G. I. Scott⁵, James Witter⁶, Hasan Yazici⁷, Raashid Luqmani⁸ - Show less +10 more•Institutions (8)

University of Birmingham¹, Maastricht University², University of Paris³, Boston University⁴, University of East Anglia⁵, Food and Drug Administration⁶, Istanbul University⁷, Nuffield Orthopaedic Centre⁸

01 May 2007-Annals of the Rheumatic Diseases

TL;DR: Recommendations for conducting clinical trials in AAV deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers.

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Abstract: Objectives: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides.

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556 citations

"Otolaryngological progression of gr..." refers background in this paper

...It is unclear whether grumbling disease is due to active inflammation, chronic infection, or chronic damage, as there is a paucity of biopsy-driven observations for patients in this disease setting.(18) Furthermore, symptoms that may have begun as active vasculitis, such as hearing loss, may over time become characterized as ‘‘chronic damage....
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...Manifestations such as nasal crusting and sinusitis have been described as ‘‘grumbling’’ disease, which has been defined as disease activity with minor symptoms that do not require a change in immunosuppressive treatments but warrant close follow-up and symptomatic treatment.(5,18) It is unclear whether grumbling disease is due to active inflammation, chronic infection, or chronic damage, as there is a paucity of biopsy-driven observations for patients in this disease setting....
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Journal Article•DOI•

Rituximab versus cyclophosphamide for ANCA-associated vasculitis

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R.S. Panush

01 Jan 2011-Yearbook of Medicine

452 citations

"Otolaryngological progression of gr..." refers background or methods in this paper

...Subglottic stenosis is also an important sequela of GPA, found in up to 16% to 23% of patients, and often requires multiple operative dilations.4,5 Furthermore, chronic serous otitis media secondary to eustachian tube dysfunction and sensorineural hearing loss are both frequently observed in patients with GPA.2 Otolaryngologists, therefore, play an integral role in the management and surveillance of patients with GPA....
[...]
...Wegener’s granulomatosis, granulomatosis with polyangiitis, rituximab G ranulomatosis with polyangiitis (GPA), historically known as Wegener’s granulomatosis, is a systemic vasculitis that affects small and medium vessels predominately in the kidneys, lungs, and the mucosa of the upper respiratory tract.1 This ANCA (antineutrophil cytoplasmic antibody)–associated disease is characterized by the histological presence of granulomatosis, vasculitis, and necrosis.2 The reported prevalence of GPA in the United States is 3 per 100,000 people, predominately in whites, with an equal sex distribution and is, on average, diagnosed in the fifth decade of life.3-5 Otolaryngological manifestations of the disease have been well documented in the literature and are found in up to 90% of patients with GPA.4-6 Granulomatosis with polyangiitis most commonly affects the sinus and nasal mucosa, which leads to epistaxis, chronic sinusitis, and rhinosinusitis....
[...]
...Since then, several case-controlled cohorts and randomized controls trials have demonstrated the efficacy of rituximab for systemic GPA.7,8,11,12,14 The efficacy of rituximab for otolaryngological manifestation of the disease, however, has been more equivocal....
[...]
...Despite this, our analysis is important in that it highlights the limitations of rituximab to fully control otolaryngological manifestations of GPA....
[...]
...In 2010, the RAVE trial showed that rituximab was noninferior to cyclophosphamide in inducing remission in patients with GPA, with the primary end point being disease flares.(7) Since then, rheumatologists have begun using...
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