https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 21/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Clinical practice varies in the monitoring of ANCA titers among patients being treated for GPA or MPA. Some authors and editors routinely monitor ANCA titers, particularly among patients with kidney involvement, to assess the response to therapy and risk of relapse [65,79-82]. Other contributors do not routinely monitor ANCA titers, since ANCA titers do not consistently reflect disease activity. Additional information about ANCA titers in patients with GPA or MPA is presented elsewhere. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Management of relapsing disease", section on 'Monitoring by the clinician'.) Additional organ-specific testing may be required for some patients. As an example, repeat CT of the chest is advised for patients with tracheal and/or pulmonary involvement to document remission or prior active disease and/or to establish a new baseline. In addition, serial audiograms should be performed in patients with any form of hearing loss related to GPA or MPA. Other treatment considerations Treatment-associated toxicity Cyclophosphamide, rituximab, azathioprine, methotrexate, mycophenolate, and glucocorticoids are all associated with important toxicity. In addition to the toxicities discussed below, cytotoxic agents are toxic to the fetus. (See "Pregnancy in patients with nondialysis chronic kidney disease" and "Safety of rheumatic disease medication use during pregnancy and lactation" and "General principles of the use of cyclophosphamide in rheumatic diseases".) Adverse effects of these drugs are discussed in separate topics: Cyclophosphamide (see "General toxicity of cyclophosphamide in rheumatic diseases") Rituximab (see "Rituximab: Principles of use and adverse effects in rheumatoid arthritis" and "Infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy", section on 'Rituximab') Azathioprine (see "Pharmacology and side effects of azathioprine when used in rheumatic diseases") Methotrexate (see "Major side effects of low-dose methotrexate") Mycophenolate (see "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases") Glucocorticoids (see "Major side effects of systemic glucocorticoids") https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 22/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Prevention of opportunistic infections and vaccinations We typically administer prophylaxis to prevent Pneumocystis jirovecii pneumonia in all patients initiating immunosuppressive therapy with cyclophosphamide or rituximab in combination with prednisone at a dose 20 mg/day (or equivalent dose of a different glucocorticoid). We discontinue prophylaxis when the dose of prednisone is tapered to less than 5 to 10 mg/day. Most commonly, we use trimethoprim-sulfamethoxazole (one single-strength [80 mg/400 mg] tablet daily or one double-strength [160 mg/800 mg] tablet three times per week). Other prophylactic regimens are discussed in detail separately (see "Treatment and prevention of Pneumocystis pneumonia in patients without HIV"). In one patient cohort, Pneumocystis pneumonia developed in 11 of 180 patients (6 percent) with GPA, all of whom were treated with daily glucocorticoids and a second immunosuppressive drug [83]. In addition to P. jirovecii pneumonia, patients treated with immunosuppressive therapy for GPA or MPA are at high risk for infections [84,85]. Given this increased risk of infection, patients should receive age-appropriate vaccinations, including those against pneumococcus, influenza, and herpes zoster (see "Immunizations in autoimmune inflammatory rheumatic disease in adults"). In one large study, for example, the cumulative incidence of infection was 51 percent during the first year of treatment [84]. Most infections involved the respiratory tract, and most positive cultures revealed Staphylococcus aureus. Management of respiratory tract and upper airway involvement The management of central airway obstruction and diffuse alveolar hemorrhage are discussed separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "The diffuse alveolar hemorrhage syndromes", section on 'Treatment'.) The consequences of upper airway involvement are often not improved by initial immunosuppressive therapy and are not considered resistant disease. Nasal ulcers and crusting are common manifestations of upper airway disease in ANCA- associated vasculitis, particularly in GPA. It is often difficult to determine whether these lesions are attributable to vasculitis, infection, or both. Although oral antibiotics are frequently required to treat more severe infections in the upper respiratory tract, some experts prefer a trial of topical therapy for nasal ulcers and crusting. This approach may involve direct application of antibiotic ointment just inside of the nares and/or nasal irrigation with a saline solution to which topical antibiotics have been added. Nasal saline sprays are available over the counter or may be made up as 1 quart of water with 1 teaspoon of brine or pickling salt and 1 teaspoon of baking soda. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 23/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Lesions of the tracheobronchial tree can cause a variety of problems. The most serious complications include tracheal or bronchial stenosis that can lead to respiratory failure or postobstructive pneumonia. Clinicians should have a low threshold for referring patients with any signs or symptoms of suspected subglottic stenosis (eg, stridor, hoarseness, or unexplained dyspnea) to an otolaryngologist familiar with this problem. Treatment options for these problems include airway dilation with or without stenting. For subglottic stenosis, intralesional injection of glucocorticoids in combination with endoscopic dilation may avoid the need for more invasive surgical procedures [86,87]. Tracheostomy should be avoided whenever possible. When tracheostomy is necessary, most patients are able to have the tracheostomy tube removed. This was illustrated in a retrospective report of 27 patients with ANCA-associated vasculitis: 11 required tracheostomy, and three could not be decannulated [88]. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".) Stenosing lesions of the nasal passages and destructive lesions of the nasal cartilage and bones may cause discomfort and/or be disfiguring. Reconstructive surgery may provide a functional airway and can restore a more normal-appearing nose [89]. Grafts prepared from a patient's costal or auricular cartilage, iliac or other bone, or dura have been used with varying success. SPECIAL POPULATIONS Pregnant patients There is only limited information on pregnancy complicated by granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) [90,91]. The major challenges in treating active disease during pregnancy are the moderate to high risk of fetal harm associated with various therapies used for induction or maintenance of remission, including cyclophosphamide, methotrexate, and mycophenolate. In addition, there are limited data regarding the safety of rituximab in pregnancy: (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Cyclophosphamide'.) (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Methotrexate'.) (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Mycophenolate mofetil'.) (See "Safety of rheumatic disease medication use during pregnancy and lactation", section on 'Rituximab'.) https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 24/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate The immunosuppressive drugs considered safer during pregnancy that have been effective in GPA and MPA include glucocorticoids, azathioprine, and cyclosporine (or tacrolimus), particularly in mild to moderate disease. These drugs can also be tried for severe disease, but such an approach may necessitate prolonged use of high-dose glucocorticoids and a slower glucocorticoid taper. Alternatives that could be considered include rituximab or cyclophosphamide in the second or third trimester once organogenesis is complete, although data are limited and the risks and benefits must be weighed carefully. The ongoing online Vasculitis Pregnancy Registry (V-PREG) study is collecting data on maternal and fetal outcomes in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (and other vasculitides) in order to provide informed guidance to patients and clinicians on the management of vasculitis during pregnancy. Older patients Among patients with GPA or MPA, it is not uncommon for patients to present with new-onset disease at age 75 years or older. Studies have demonstrated that older age is an independent risk factor for worse outcomes in ANCA-associated vasculitis, both due to life- threatening infections and to disease-related morbidity, notably end-stage kidney disease (ESKD) [92,93]. The increased risk of serious infections in older patients and the substantive risk of infection associated with glucocorticoids highlight the need to use "glucocorticoid-sparing" approaches in this patient population. Older patients with ANCA-associated vasculitis respond well to the same treatment approaches to induction of remission as do younger patients [24], and use of rituximab or cyclophosphamide (in reduced dosing based on kidney function and age) should not be withheld due to age. Regimens to maintain remission in ANCA-associated vasculitis are especially important for older patients to avoid repeat use of glucocorticoids and to preserve residual kidney function. However, as with all treatment of ANCA-associated vasculitis, the risks of prolonged immunosuppression and infection must be weighed against the benefits of avoiding a relapse of vasculitis. Patients with end-stage kidney disease Maintenance dialysis Little is known concerning the optimal treatment of patients with GPA or MPA who develop ESKD and require maintenance dialysis. Such patients have a higher risk of death as compared with patients who do not develop ESKD. (See 'Prognosis and other outcomes' below.) Further management varies with the clinical setting: https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 25/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate No active disease If the patient has no evidence of active kidney disease (ie, absence of hematuria with dysmorphic red cells in the urine sediment, which must be distinguished from isomorphic [normomorphic] hematuria that may be due to cyclophosphamide- induced bladder injury) and has no active extrarenal disease, we continue immunosuppressive therapy until the patient has completed three to six months of maintenance therapy. If, at that time, the patient continues to have inactive disease, then we typically discontinue immunosuppressive therapy. (See 'Maintenance therapy' above.) It is unclear how much benefit is provided by usual maintenance therapy to prevent relapse in patients with ESKD since the rate of relapse is substantially reduced in dialysis [94,95]. In an analysis of 229 patients on maintenance dialysis followed for a mean of 4.6 years, the relapse rate decreased from 57 to 7 episodes per 100 person-years before and after dialysis initiation [95]. During the follow-up period, 45 percent of patients had a serious infection and 45 percent had a cardiovascular event, while 13 percent experienced disease relapse. Active kidney but not extrarenal disease If the patient has persistent dysmorphic hematuria and no extrarenal disease, we treat with immunosuppressive therapy in a manner similar to patients without ESKD with appropriate dose adjustments in medications for the kidney failure. The purpose of continued therapy in patients with active kidney but without extrarenal manifestations is that control of the renal vasculitis might result in enough recovery of kidney function to permit the discontinuation of dialysis. However, treating such patients beyond four months is of limited benefit [96]. (See 'Induction therapy' above and 'Maintenance therapy' above.) Active extrarenal disease We and other investigators treat patients on chronic dialysis with active extrarenal GPA or MPA in the same manner as those who do not require maintenance dialysis, with the duration of therapy and therapeutic regimen being based upon patient response and whether relapse has occurred and with appropriate dose adjustments in medications for the kidney failure. (See 'Induction therapy' above and 'Maintenance therapy' above.) Even if a decision is made to discontinue immunosuppressive therapy in patients on chronic dialysis, it is imperative that all patients with a history of GPA or MPA be followed indefinitely for the potential to relapse in other organ systems, even many years following the onset of kidney failure. The following immunosuppressive drugs should either not be used or not be used at standard doses in patients with ESKD: https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 26/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Methotrexate should not be given as maintenance therapy to patients who are on dialysis or have moderate to severe chronic kidney disease. Given the increased risk of severe bone marrow suppression in patients with ESKD, cyclophosphamide should be used cautiously with careful monitoring. Dose adjustment for cyclophosphamide in dialysis patients is not well defined. A suggested approach for oral cyclophosphamide is 50 percent of the usual dose after each hemodialysis session and 75 percent of the usual dose in patients on continuous ambulatory peritoneal dialysis ( table 1). Kidney transplantation Patients who develop ESKD due to GPA or MPA are potential candidates for kidney transplantation. At a minimum, transplantation should be delayed for at least six months from the time of initial presentation or most recent relapse [97]. The presence of a positive ANCA titer at the time of transplantation does not appear to predict recurrence of glomerulonephritis in the transplanted organ. Thus, persistence of an isolated positive ANCA titer is not a contraindication to kidney transplantation. It is likely that the immunosuppression administered for the prevention of allograft rejection contributes to the prevention of disease flares among patients with GPA or MPA [98,99]. Several studies have shown that long-term outcomes of patients with GPA or MPA who receive a kidney transplant are comparable to those of patients transplanted for other causes of ESKD [100-103]. Drug-induced ANCA-associated vasculitis Certain medications (eg, hydralazine, propylthiouracil, minocycline) may induce vasculitis associated with antineutrophil cytoplasmic autoantibody (ANCA), mostly myeloperoxidase (MPO)-ANCA. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Drug-induced ANCA-associated vasculitis'.) The optimal management of drug-associated ANCA and the course of the disease are uncertain given the limited reports in the literature. Discontinuation of the offending agent may be the only intervention necessary for mild cases of ANCA-associated vasculitis induced by medications. Examples include cases presenting with constitutional symptoms, arthralgias/arthritis, or cutaneous vasculitis, but without lung or kidney involvement. Patients with more severe disease manifestations such as lung or kidney involvement, which are common with hydralazine, require treatment with high doses of glucocorticoids and even rituximab or cyclophosphamide. As an example, in one series of 80 cases of hydralazine-induced ANCA-associated glomerulonephritis, 42 of 51 patients with long-term follow-up received https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 27/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate immunosuppressive therapy [104]. (See 'Induction therapy' above and "Clinical spectrum of antineutrophil cytoplasmic autoantibodies", section on 'Hydralazine'.) Patients with drug-induced ANCA-associated vasculitis do not typically require maintenance therapy; relapse should not occur if the responsible drug is discontinued. However, attributing ANCA-associated vasculitis to a drug may be incorrect, and therefore careful and frequent monitoring of the patient is required after discontinuation of the presumed causative agent. The risk of recurrence with re-exposure to the drug is unclear. Given the potential morbidity associated with drug-induced ANCA-associated vasculitis, we do not advocate for rechallenge with the potentially offending agent. Double-positive ANCA and anti-GBM disease Patients who are double positive for antineutrophil cytoplasmic autoantibody (ANCA) and anti-glomerular basement membrane (anti- GBM) antibodies should be managed initially as patients with anti-GBM disease since this is the more severe lesion. The initial treatment of such patients should include plasmapheresis plus immunosuppressive therapy, even among those with dialysis-requiring kidney failure. These issues are discussed in more detail elsewhere. (See "Anti-GBM (Goodpasture) disease: Treatment and prognosis", section on 'Double-positive anti-GBM and ANCA-associated disease'.) However, unlike patients with single-positive anti-GBM disease, double-positive patients will require maintenance therapy for ANCA disease because of the tendency of vasculitis to relapse. (See 'Maintenance therapy' above.) INVESTIGATIONAL APPROACHES Several investigational agents have been tried or are under investigation for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), including abatacept [105], belimumab [106], vilobelimab, and B cell-targeted immunotherapy [107]. Additional studies are required before these therapies can be routinely used in clinical practice. PROGNOSIS AND OTHER OUTCOMES Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are associated with considerable morbidity and mortality that are due to either irreversible organ dysfunction from inflammatory injury or the consequences of prolonged and/or intensive therapy with glucocorticoids and other immunosuppressive agents: https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 28/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Mortality Untreated patients have a 90 percent mortality rate within two years. The long- term survival in patients with GPA and MPA has improved dramatically since the additions of cyclophosphamide and rituximab to the therapeutic regimen [108,109]. However, patients with GPA and MPA still have a higher mortality rate compared with the general population [110,111]. A meta-analysis of observational studies of patients with GPA and MPA reported a 2.7-fold increased risk of death in patients compared with the general population (95% CI 2.26-3.24) [110]. The major causes of death in patients with GPA and MPA are complications from immunosuppressive therapy (primarily infection), complications from the underlying disease (eg, kidney failure, pulmonary failure), and cardiovascular disease [94,112-114]. Higher mortality rates are observed among older adults and those who present with florid organ failure, such as patients with diffuse pulmonary hemorrhage requiring ventilatory support or advanced kidney dysfunction [115,116]. End-stage kidney disease (ESKD) and overall mortality are higher in older adult patients (age >80 years). As an example, a retrospective study including 78 patients >80 years old who had biopsy-proven pauci- immune glomerulonephritis, of whom 93 percent had a positive ANCA, found that ESKD was more common in the untreated group at one year (73 versus 36 percent) [117]. Malignancy risk Some studies suggest that patients with GPA or MPA may have a higher incidence of cancer compared with the general population, with estimates ranging from 10 to 26 percent [118]. The increased risk of malignancy has been described with non- melanoma skin carcinomas (NMSCs), hematologic malignancies, and bladder, breast, lung, prostate, and colorectal carcinomas [119,120]. To some degree, some of the increased risk is associated with immunosuppressive treatment [121]. As treatment regimens for GPA and MPA have evolved over the past decade to include shorter courses of cyclophosphamide, more contemporary studies have suggested that the risk of cancer may be decreasing [119,122]. Infection Approximately 25 to 30 percent of patients with GPA and MPA will develop a serious infection that requires hospitalization, with respiratory infections being the most common [123-126]. Patients are at highest risk for infection in the first year after diagnosis, which is most likely related to the higher intensity of immunosuppression during this time period, including the use of high-dose glucocorticoids [123,127,128]. The use of immunosuppressive agents to treat GPA and MPA is a primary factor contributing to the risk of infection in these patients. Several studies have evaluated the risk of infection associated with different immunosuppressive regimens used to treat GPA https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 29/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate or MPA. As an example, two randomized trials found no difference in infection rates between patients receiving a rituximab-based regimen and those receiving a cyclophosphamide-based regimen as induction therapy [19,21]. Trials comparing different maintenance regimens have reported similar rates of infection among patients treated with azathioprine, methotrexate, mycophenolate mofetil, rituximab, or oral cyclophosphamide [18,54-56]. End-stage kidney disease Since the kidney is a frequent target organ in patients with either GPA or MPA, progressive kidney failure may be observed. In different series with a variable duration of follow-up, ESKD occurred in 10 to 26 percent of patients [2,94,112,115,129-132]. The incidence of ESKD among patients with GPA and MPA has fallen over the past several decades. In a study of an inception cohort of 554 patients with kidney disease at time of diagnosis, the five-year risk of ESKD decreased over time [108]. Serum creatinine at baseline was the only significant predictor of risk of ESKD. The principal determinants of a poor kidney outcome include more severe kidney dysfunction at presentation, lack of response to initial treatment, renal relapses, age greater than 65 years, and prominent fibrotic changes, such as interstitial fibrosis and glomerulosclerosis on initial kidney biopsy [2,115,129,133-135]. By comparison, responsiveness to immunosuppressive therapy and improved kidney function over time can be observed among patients with predominantly active kidney lesions at disease presentation. Severe initial kidney involvement does not preclude the induction of remission or clinically significant improvement in kidney function with appropriate therapy. In a report of newly diagnosed patients, remission was induced in 72 percent of 240 patients with an estimated 3 2 glomerular filtration rate (eGFR) 30 mL/min/1.7 m , 68 percent of 188 patients with an 2 2 eGFR 20 mL/min/1.73 m , and 57 percent of 96 patients with an eGFR 10 mL/min/1.73 m [129]. On the other hand, severe kidney disease at presentation was also a risk factor for cyclophosphamide resistance (odds ratio 1.28 per 1.13 mg/dL [100 micromol/L] elevation in serum creatinine). Among patients who require dialysis during the acute phase of the disease, 55 to 90 percent recover enough function to come off dialysis [3,115,129,136-138], with 40 to 70 percent being maintained off dialysis for three years or more [3,139]. Cardiovascular risk Patients with GPA or MPA may have an increased risk of cardiovascular events, including thromboembolism [140-146]. In a cohort study that examined cardiovascular events among 2306 patients with GPA or MPA and 6918 controls, https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 30/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate a diagnosis of GPA or MPA was associated with an increased risk of ischemic heart disease (HR 1.86, 95% CI 1.62-2.15), heart failure (HR 2.12, 95% CI 1.77-2.54), myocardial infarction (HR 1.62, 95% CI 1.26-2.09), atrial fibrillation (HR 2.08, 95% CI 1.82-2.39), ventricular arrhythmia/defibrillator implantation (HR 2.04, 95% CI 1.16-3.57), and ischemic stroke (HR 1.58, 95% CI 1.31-1.90) [142]. Patients with GPA or MPA also had an increased risk of undergoing percutaneous coronary intervention (HR 1.56, 95% CI 1.17-2.07) and in-hospital cardiac arrest (HR 2.27, 95% CI 1.49-3.48). The reasons for an increased risk of cardiovascular disease among patients with GPA and MPA are not clear, but some investigators speculate this may relate to the impact of nontraditional risk factors, including chronic inflammation, use of glucocorticoids, and chronic kidney disease. As an example, in a retrospective multinational study of 2286 patients with ANCA-associated vasculitis, risk factors for myocardial infarction and stroke included pulmonary and kidney involvement (HR 1.5 and 3.0, respectively), older age, and history of smoking [147]. Clinicians and patients are advised to be vigilant about evaluating and treating established risks of cardiovascular disease, including hypertension, diabetes mellitus, hyperlipidemia, and obesity; these comorbidities may be more prevalent among patients with GPA and MPA. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Glomerular disease in adults" and "Society guideline links: Vasculitis".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 31/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Granulomatosis with polyangiitis (The Basics)") Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Goals of therapy The goal of therapy in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) is to achieve a rapid, long-standing remission. Treatment consists of an initial induction phase aimed to put patients with active disease into remission, followed by a maintenance phase that is intended to extend remission and prevent relapse. (See 'Goals of therapy' above.) Approach to initial therapy Immunosuppressive therapy is warranted in almost all patients with active GPA or MPA. Our approach to initial therapy depends largely upon the severity of disease and the organ systems involved ( algorithm 1): Organ- or life-threatening features include, but are not limited to, active glomerulonephritis, pulmonary hemorrhage, cerebral vasculitis, progressive peripheral or cranial neuropathy, orbital pseudotumor, gastrointestinal bleeding due to vasculitis, or cardiac disease due to vasculitis (pericarditis, myocarditis). Patients with non-organ- or non-life-threatening disease have no evidence of "active glomerulonephritis" (ie, serum creatinine that is stable compared with baseline and no red cell casts or proteinuria) and no organ-threatening or life-threatening manifestations. (See 'Assessment of disease severity' above.) Organ- or life-threatening disease Induction therapy Rituximab- or cyclophosphamide-based regimen For patients with GPA or MPA who have organ- or life-threatening disease, we recommend an induction regimen consisting of glucocorticoids in combination with either rituximab or cyclophosphamide, rather than glucocorticoid monotherapy (Grade 1B). Some authors/editors choose a rituximab-based regimen for the majority of patients, given its comparable efficacy and different side-effect profile compared with https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 32/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate cyclophosphamide. Other authors/editors favor a cyclophosphamide-based regimen as initial therapy, particularly in patients presenting with more severe kidney disease and/or pulmonary hemorrhage. Some authorities treat with glucocorticoids in combination with both rituximab and cyclophosphamide. (See 'Induction therapy' above.) Glucocorticoid dosing For most patients with GPA or MPA receiving glucocorticoids in combination with a glucocorticoid-sparing agent, we recommend a reduced-dose glucocorticoid tapering regimen rather than the standard-dosing taper (Grade 1B). Dosing of glucocorticoids is discussed above. (See 'Glucocorticoid dosing and taper' above.) Role of plasma exchange The authors/editors of this topic do not fully agree on the role of plasma exchange among patients with GPA or MPA. All authors agree with the use of plasma exchange in most patients with GPA or MPA who are concomitantly positive for anti-glomerular basement membrane (anti-GBM) autoantibody. Other authors would also offer plasma exchange in patients who present with pulmonary hemorrhage and/or severe active kidney disease with kidney biopsy findings showing active inflammation without significant glomerulosclerosis. (See 'Role of plasma exchange' above.) Maintenance therapy In most patients who achieve remission after induction immunosuppressive therapy, we suggest treatment with rituximab for maintenance of remission (Grade 2C). Azathioprine, methotrexate, and mycophenolate are reasonable alternatives and may be preferred based on other patient-specific factors. Maintenance therapy in patients with newly diagnosed GPA or MPA is usually given for 12 to 24 months after stable remission has been induced. (See 'When to start maintenance therapy' above and 'Choice of maintenance therapy' above and 'Dosing of maintenance therapy' above and 'Duration of maintenance therapy' above.) Non-organ- and non-life-threatening disease Patients with non-organ- or non-life- threatening disease have no evidence of "active glomerulonephritis" (ie, serum creatinine that is stable compared with baseline and no red cell casts or proteinuria) and no organ- threatening or life-threatening manifestations. For patients with non-organ- and non-life- threatening GPA not involving the kidney, we suggest initial therapy with glucocorticoids combined with weekly oral methotrexate rather than glucocorticoids combined with cyclophosphamide, rituximab, or azathioprine (Grade 2C). Rituximab is a reasonable alternative as initial therapy, even in non-organ- and non-life-threatening disease. Azathioprine may be used as an alternative to methotrexate for pregnant patients or https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 33/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate patients for whom methotrexate should be avoided due to moderate to severe kidney function impairment. (See 'Non-organ- and non-life-threatening disease' above.) Monitoring All patients receiving immunosuppressive therapy for GPA or MPA should be closely monitored. Patients with organ- or life-threatening disease are typically admitted to the hospital for treatment with close monitoring of their clinical status and laboratory testing on a daily basis. When the patient's condition is stable enough for discharge from the hospital, we typically schedule follow-up visits every two to four weeks for the first three months. Subsequently, the duration between follow-up visits can then be extended to every two to three months. The goal of these visits is to evaluate the patient's response to therapy and the toxicity of the regimen. (See 'Monitoring the response to therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Stone JH, Hoffman GS, Merkel PA, et al. A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum 2001; 44:912. 2. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116:488. 3. Nachman PH, Hogan SL, Jennette JC, Falk RJ. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996; 7:33. 4. Mahr AD, Neogi T, Lavalley MP, et al. 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Remission and Low Disease Activity in Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Prevalence and Impact on Damage Accrual. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 34/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Arthritis Care Res (Hoboken) 2023; 75:1158. 9. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody- Associated Vasculitis. Arthritis Care Res (Hoboken) 2021; 73:1088. 10. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1. 11. 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