GPA granulomatosis with polyangitis treatment with steroid and cyclophosphamide
- related: Wegener GPA granulomatosis with polyangitis
- tags: #literature #icu #pulmonology
It’s important to know if you are treating with induction or just maintenance.
For patients with life-threatening disease or organ failure, such as in this case, the induction phase of treatment entails a combination of high dose glucocorticoids and either cyclophosphamide or rituximab.
Glucocorticoids alone have not been shown to be an effective therapy against severe disease (may be able to use for non life threatening diseases).
Initial immunosuppressive therapy typically consists of cyclophosphamide and prednisone, with plasma exchange added in cases, such as this one, with organ-threatening disease, such as pulmonary hemorrhage or deteriorating renal function.
Plasma exchange may play a role in the treatment of granulomatosis with polyangiitis under certain circumstances, but its use is controversial. Consensus expert opinion would consider plasma exchange if the individual is positive for antiglomerular basement membrane, if steroids and cyclophosphamide/rituximab have failed, or if the patient has severe renal disease. Although this patient has severe renal disease, his treatment has not failed, and methylprednisolone and cyclophosphamide should be administered first.123
Maintenance therapy includes azathioprine, mycophenolate mofetil, or rituximab for at least 12 to 24 months after stable remission has been achieved. Glucocorticoids alone are insufficient to control GPA. Patients with nonsevere forms of GPA (such as arthropathy or upper airway disease) without organ-threatening disease can be treated with glucocorticoids plus either methotrexate or mycophenolate mofetil; such patients should be carefully monitored for treatment failure or the development of renal or other organ-threatening disease, necessitating the more aggressive regimen. Using these approaches, GPA mortality has declined from 90% to around 10%.
The RAVE (Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis) trial demonstrated that rituximab is superior to cyclophosphamide in the subgroup of patients with relapse. In this study, remission without prednisone at 6 months was observed in 67% of rituximab-treated patients compared with 42% of cyclophosphamide patients (P = 0.01; NNT = 4). Rituximab was also as effective as cyclophosphamide in the treatment of patients with kidney disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events.
In trials of etanercept treatment for GPA, patients manifested an increased risk for the development of solid malignancies, especially if they had previously been treated with cytotoxic drugs. Therefore, etanercept is not considered first-line treatment for GPA.
Corticosteroids such as prednisone are not considered adequate single-drug maintenance therapy in GPA. The addition of corticosteroids to another agent used for maintenance therapy is not recommended, as trials suggest that it results in a greater number of infections but not a decreased risk of GPA relapse.
Mycophenolate mofetil appears inferior to azathioprine for maintenance therapy after remission has been achieved in GPA, and it offers no advantages over azathioprine in terms of the frequency of adverse medication events.
Cyclophosphamide and azathioprine appear to be equally efficacious for GPA maintenance therapy; however, concerns regarding an increased risk of secondary malignancy when cyclophosphamide is used make the drug a less optimal choice than azathioprine for maintenance therapy.
Methotrexate is inadequate as induction therapy for severe disease; it can be used alone either as maintenance therapy after induction, or for mild and limited disease.
Relapses are common (>50% 5 years after initial remission) and may respond better to rituximab than to cyclophosphamide.
This patient has evidence of a non–organand non–life-threatening relapse of his granulomatosis with polyangiitis (GPA) after discontinuation of his maintenance therapy. In this situation, it is most appropriate to restart his prior rituximab maintenance therapy, usually in combination with a short course of glucocorticoids. In addition to rituximab, other common agents that could be used for GPA maintenance monotherapy include azathioprine, methotrexate, and mycophenolate.
While cyclophosphamide is useful as an induction agent in combination with glucocorticoids, the toxicity of the drug makes it a poor choice for maintenance therapy, and this patient does not have an organor life-threatening relapse that requires reinduction therapy that could include cyclophosphamide. If his relapse were associated with organor life-threatening disease, or if a non–organand non–life-threatening relapse occurred during ongoing maintenance therapy and did not respond to higher doses of the maintenance agent, full reinduction therapy with glucocorticoids and either cyclophosphamide or rituximab would have been indicated.
Both cyclosporine and leflunomide have immunomodulatory effects; however, neither has an established role in the treatment of GPA.
Kidney failure and infection are the main causes of mortality.4
Links to this note
-
GPA granulomatosis with polyangitis symptoms include cavitary lung disease and neuropathy
- Approximately 50% of patients with GPA have neurologic symptoms, most commonly headache or mononeuritis multiplex. Approximately 10% of patients will have imaging evidence of small-vessel vasculitis in the brain or spinal cord, which may lead to ischemic strokes, hemorrhage, or white matter lesions on MRI, as were seen in our patient. Liver involvement is also common and portends a poorer prognosis, as does the absence of sinus symptoms. In contrast, the absence of renal disease is associated with better outcomes. Treatment usually consists of glucocorticoids combined with rituximab or cyclophosphamide. In the setting of rapidly progressive renal failure or severe alveolar hemorrhage, plasma exchange may be useful (GPA granulomatosis with polyangitis treatment with steroid and cyclophosphamide).
Footnotes
-
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(4S):S1-S276. PubMed ↩
-
Sacoto G, Boukhlal S, Specks U, et al. Lung involvement in ANCA-associated vasculitis. Presse Med. 2020;49(3):104039. PubMed ↩
-
Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. PubMed ↩