Published October 8, 2023
Introduction
Polypharmacy, defined as the simultaneous use of multiple medications, has become a pressing concern in healthcare, particularly among older patients. The origin of polypharmacy is often innocuous, with patients initially prescribed medications for specific conditions. However, as individuals age and new health issues arise, the list of medications tends to grow, creating complex and sometimes risky medication regimens.
In the realm of geriatric medicine, physicians often grapple with extensive drug charts and the challenge of identifying all prescribed medications, especially when patients lack clear documentation or have memory impairments. To assist patients in managing their medications, tools like weekly pill organizer boxes were created to help organize and track various medications taken at different times.
The inherent danger of polypharmacy lies in the difficulty of discontinuing medications once they’ve been prescribed. Dose escalation becomes more common, and physicians frequently continue prescribing existing medications when patients present new health concerns without reevaluating their necessity.
To address the issue of polypharmacy, healthcare providers must conduct thorough reviews of legacy medications’ necessity and be willing to cease prescribing those that are no longer required. Pharmacists also play a vital role in identifying potential drug interactions and recommending streamlined treatment regimens.
Maintenance Therapy in AAV
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare autoimmune disorders characterized by inflammation and damage to small blood vessels, resulting in various clinical manifestations, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Achieving remission and maintaining it in AAV patients is a clinical priority.
A study conducted by Roccatello and colleagues and published in Autoimmune Reviews raised a pertinent question: should maintenance therapy be discontinued once clinical remission is achieved in AAV patients? This query shifts the focus from determining the optimal form of maintenance therapy to questioning its necessity when patients reach clear therapeutic thresholds.
Current Practices in Maintenance Therapy
Maintenance therapy in AAV aims to reduce the frequency of relapses, which can significantly disrupt patients’ lives. In a study published in the Annals of the Rheumatic Diseases, Smith and colleagues compared two commonly prescribed drugs for maintaining remission in AAV: rituximab and azathioprine.
Previous studies suggest that rituximab is superior to azathioprine in preventing major relapses following cyclophosphamide induction therapy. However, concerns linger about the long-term use of rituximab, including an increased risk of infection and the development of hypogammaglobulinemia.
Smith and colleagues conducted the RITAZAREM trial to assess the efficacy of fixed-interval rituximab compared to azathioprine for maintaining remission after initial remission induction. The rituximab group received intravenous therapy of 1000 mg every 4 months for 5 doses, while the azathioprine group received oral therapy at 2mg/kg/day for 24 months, followed by a gradual reduction and treatment withdrawal at month 27.
The trial enrolled 170 patients, with 85 in each group. The results confirmed that rituximab was indeed superior to azathioprine in preventing major/minor disease relapses. At month 24, the rituximab group had a relapse-free survival rate of 0.85, compared to 0.73 in the azathioprine group. During the follow-up phase, 33 relapses occurred in the rituximab group and 49 in the azathioprine group.
The conclusion drawn from the RITAZAREM trial was that repeat-dose rituximab is more effective than azathioprine for preventing relapses in AAV patients. Future treatment strategies for AAV may need to adopt a more individualized approach, weighing the risk of relapse against the risk of adverse events with extended treatment.
Is Maintenance Therapy Necessary?
Although international guidelines recommend maintenance therapy, at least for a period, there are valid questions about its necessity once patients achieve persistent clinical remission.
Roccatello and colleagues’ study explored the scientific basis for discontinuing maintenance therapy after clinical remission. Approximately 75% of AAV patients became ANCA-negative after induction therapy, with differences between patients with myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA.
Based on the available evidence, the research team proposed two approaches, depending on ANCA specificity. For patients with MPO-ANCA who achieve clinical remission, they recommended on-demand maintenance therapy if they remain ANCA-positive and no maintenance therapy by default if they become ANCA-negative. For PR3-ANCA patients, they suggested fixed-dose rituximab if ANCA-positive and on-demand rituximab maintenance therapy if ANCA-negative.
In answering the question of whether maintenance therapy is clinically necessary once remission is achieved, patient preferences and individual risk factors for relapse should be considered. In summary, there is enough evidence to suggest that maintenance therapy can be tapered when clinical remission is attained, but this approach should be undertaken cautiously with ongoing medical supervision.
It’s essential for clinicians to remain responsive to evolving evidence, especially considering the likelihood that our current methods for inducing and maintaining remission will become outdated as newer therapeutics emerge. The decision to discontinue maintenance therapy in AAV should be based on a careful evaluation of individual patient factors and the best available scientific evidence.
References:
Roccatello D, Padoan R, Sciascia S, Iorio L, Nic An Ríogh E, Little MA. Might maintenance therapy be discontinued once clinical remission is achieved in ANCA-associated vasculitis? Autoimmun Rev. 2023;103438. doi:10.1016/j.autrev.2023.103438
Smith RM, Jones RB, Specks U, et al. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial. Ann Rheum Dis. 2023;82(7):937-944. doi:10.1136/ard-2022-223559
