Rituximab For Maintenance Of Remission Research Articles

Pituitary hypophysitis in granulomatosis with polyangiitis (GPA): a case series

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects.

Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1—treatment of granulomatosis with polyangiitis and microscopic polyangiitis

ObjectiveTo summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis (AAV).MethodsA systematic literature review (SLR) was performed to...

New Treatment Options for Pituitary Granulomatosis With Polyangiitis

Background: Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland and has been reported in 1% of all cases of GPA. Most frequently, it presents with pituitary mass effect and diabetes insipidus (DI). To date, there are no treatment guidelines for this rare condition. Case Presentation: Case 1: A 55 year old female with a history of ANCA-positive pulmonary GPA, previously treated with glucocorticoids and immunosuppressants, presented two years later with cranial DI and bitemporal hemianopia. MRI showed a large sellar mass with suprasellar extension. High dose glucocorticoids resulted in good clinical and radiological response. Further treatment consisted in a combination of Cyclophosphamide and Rituximab (RTX). Further doses of RTX are planned aiming for a period of B-cell depletion. Case 2: A 38 year old female, presented with polyuria, recurrent nosebleeds, headaches and a left visual field defect. Pituitary profile revealed ACTH deficiency and MRI showed a heterogenous cystic lesion with peripheral enhancement and stalk thickening. Steroid replacement led to immediate improvement in her symptoms. Cranial DI was confirmed and raised Proteinase 3 (PR3) antibody suggested GPA. A combination of prednisolone and Methotrexate led to significant improvement of MRI appearances and declining PR3 antibody levels. For remission maintenance, two cycles of RTX were given with further radiological and biochemical improvement, and, following dynamic assessment of her HPA axis, she could be fully weaned off steroids. Case 3 is a 47 year old female with a history of childhood asthma. She was found to have cavitating lung lesions. ANCA positivity confirmed GPA and she was commenced on high-dose steroids. During follow-up, she developed headache, polyuria and polydipsia. MRI pituitary showed a suprasellar lesion and pituitary biopsy revealed inflammatory hypophysitis. Cranial DI was confirmed by water deprivation testing. Previous allergic reactions to both RTX and Ofatumumab precluded anti-CD40 monoclonal antibodies and she was commenced on Azathioprine. A further recurrence of pituitary GPA necessitated escalation of the steroid dose and switch of azathioprine to mycophenolate mofetil. She remains in remission and her steroids reduced to a maintenance dose. Conclusion: GPA pituitary has been observed to occur at variable time after diagnosis often in the absence of any other systemic features. A combination of glucocorticoids and RTX has been approved for severe relapsing pulmonary GPA, however, limited data is available for pituitary GPA. In this case series, the response to high dose steroids and RTX for remission maintenance has been encouraging. Experience with ‘conventional’ immunosuppresants remains limited and therapeutic responses remain variable. Further clinical studies are required to establish effective treatment for pituitary GPA.

Rituximab for maintenance of remission in ANCA-associated vasculitis: expert consensus guidelines-Executive summary.

© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Considerable improvements in therapy mean induction of remission occurs in most patients with AAV [1-4]. However, disease relapse continues to pose a burden to patients. Morbidity accrues with relapses through disease-related damage and adverse effects of therapies to manage these relapses, negatively impacting on quality of life [5]. Rituximab (RTX), a monoclonal antibody targeting CD20, leads to peripheral B cell depletion. This has been successfully trialled, and is licensed, for the induction and maintenance of remission in AAV [2, 3]. RTX is increasingly being used for the maintenance of remission in patients with AAV, to reduce the risk of relapse and its consequences [6]. Other commonly used agents that have been trialled for the maintenance of remission in AAV include azathioprine, methotrexate and mycophenolate [7-9]. The decision to select RTX for the maintenance of remission is multifactorial, including but not limited to, patient-related factors and preferences, previous treatment and response, consideration of the overall risk of relapse, and access to therapy. These guidelines have been developed by a group of physicians practising in the UK.

Clinical trials. Rituximab for maintenance of remission in AAV.

Maintenance therapy for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) should reduce rates of relapse with minimal toxicity. The MAINRITSAN trial—the first randomized controlled trial to compare the efficacies of rituximab and azathioprine in AAV remission maintenance— has demonstrated a superior outcome using rituximab. These data have important implications for the management of AAV.

Experience with rituximab in the treatment of antineutrophil cytoplasmic antibody associated vasculitis.

Prior to the 1970s, severe cases of antineutrophil cytoplasmic antibody associated vasculitis (AAV) were thought to be invariably fatal. However, the use of cyclophosphamide-based treatment regimens fundamentally altered disease outcomes, transforming AAV into a manageable, chronic illness. Despite the tremendous success of cyclophosphamide in the treatment of AAV, there remained a need for alternative therapies, due to high rates of treatment failures and significant toxicities. In recent years, with the introduction of targeted biologic response modifiers into clinical practice, many have hoped that the treatment options for AAV could be expanded. Rituximab, a chimeric monoclonal antibody directed against the B-lymphocyte protein CD20, has been the most successful biologic response modifier to be used in AAV. Following the first report of its use in AAV in 2001, experience with rituximab for treatment of AAV has rapidly expanded. Rituximab, in combination with glucocorticosteroids, is now well established as a safe and effective alternative to cyclophosphamide for remission induction for severe manifestations of granulomatosis with polyangiitis and microscopic polyangiitis. In addition, initial experiences with rituximab for remission maintenance in these diseases have been favorable, as have experiences for remission induction in eosinophilic granulomatosis with polyangiitis.

Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody–associated vasculitis

Rituximab is effective induction therapy in refractory or relapsing antineutrophil cytoplasmic antibody-associated vasculitis (AAV). However, further relapse is common, and maintenance strategies are required. The aim of this study was to reduce relapse rates using a fixed-interval rituximab re-treatment protocol. Retrospective, standardized collection of data from sequential patients receiving rituximab for refractory or relapsing AAV at a single center was studied. Group A patients (n = 28) received rituximab induction therapy (4 infusions of 375 mg/m(2) or 2 infusions 1 gm) and further rituximab at the time of subsequent relapse. Group B patients (n = 45) received routine rituximab re-treatment for 2 years: 2 doses of 1 gm each for remission induction, then 1 gm every 6 months (total of 6 gm). Group C patients (n = 19) comprised patients in group A who subsequently relapsed and began routine re-treatment for 2 years. Response (complete/partial remission) occurred in 26 of the 28 patients (93%) in group A, 43 of the 45 patients (96%) in group B, and 18 of the 19 patients (95%) in group C. At 2 years, relapses had occurred in 19 of 26 patients (73%) in group A, 5 of 43 (12%) in group B (P < 0.001), and 2 of 18 (11%) in group C (P < 0.001). At the last followup (median of 44 months), relapses had occurred in 85% of those in group A (22 of 26), 26% of those in group B (11 of 43; P < 0.001), and 56% of those in group C (10 of 18; P = 0.001). Glucocorticoid dosages were decreased and immunosuppression therapy was withdrawn in the majority of patients. Routine rituximab re-treatment was well tolerated, and no new safety issues were identified. Two-year, fixed-interval rituximab re-treatment was associated with a reduction in relapse rates during the re-treatment period and a more prolonged period of remission during subsequent followup. In the absence of biomarkers that accurately predict relapse, routine rituximab re-treatment may be an effective strategy for remission maintenance in patients with refractory and relapsing AAV.

ANCA vasculitis: time for a change in treatment paradigm? Not yet

The ANCA-associated vasculitides (AAVs) are conventionally treated with a strategy of remission induction followed by maintenance therapy using glucocorticoids combined with CYC during induction and AZA for maintenance. Recently, several randomized controlled trials have been published that question whether these drugs should remain those of choice. B-cell depletion using rituximab is at least as effective as CYC for remission induction in newly presenting patients, but long-term efficacy, safety and cost-effectiveness data are awaited, and thus rituximab should be reserved for patients at high risk of infertility. Rituximab seems to be effective at inducing remission in relapsing patients. Whether routine pre-emptive treatment with rituximab for remission maintenance is a better approach than waiting for relapse is unknown. MTX and LEF have similar efficacy to AZA, but are not significantly safer; while MMF is less effective. Thus, AZA remains the conventional maintenance drug of choice.