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Treating IgAN Part 2

CE / CME

Ask the Experts: Your Questions on Treating IgAN in Clinic Today (Part 2)

ABIM MOC: maximum of 0.25 Medical Knowledge MOC point

Physician Assistants/Physician Associates: 0.25 AAPA Category 1 CME credit

Nurses: 0.25 Nursing contact hour

Physicians: maximum of 0.25 AMA PRA Category 1 Credit™

Released: December 22, 2023

Expiration: December 21, 2024

CME/CE Information

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Key Takeaways
  • There are numerous biologics, and their efficacy in IgAN has yet to be proven.
  • For targeted-release budesonide, the dose is fixed at 16 mg daily, but it is recommended to reduce to 8 mg daily for 2 weeks prior to discontinuation because of potential steroid withdrawal effects.
  • Healthcare professionals should advocate for their patients to any reluctant payers, familiarize themselves with the available financial assistance programs for IgAN therapies, and understand the magnitude of benefit of the specific prescription (compared with its alternatives) to better counsel patients about their out-of-pocket costs and available resources that can help.

As the treatment landscape of immunoglobulin A nephropathy (IgAN) continues to expand, novel therapies should be well understood and optimized to meet patients’ unique needs. In this expert commentary, we expand on answers to the questions learners submitted in the “Experts on the Ground: Data Updates on Emerging Therapies for IgAN” learning module. Be sure to review our expert commentary and answers to more learner questions in Part 1.

Can you discuss the use of biologics to treat IgAN and expected adverse events? 

Richard Lafayette, MD, FACP:
There are numerous biologics, and their efficacy in IgAN has yet to be proven. Early studies suggest that complement and B-cell inhibition through a B-cell–activating factor/proliferation-inducing ligand blockade may be effective in a broad cross-section of patients with IgAN. Although studies proving the efficacy and safety of these therapies are ongoing, they have been well tolerated except for the rare infusion reaction. There is no overall evidence of excess infections (assuring vaccination or prophylactic antibiotics for complement inhibitors) and no reported serious adverse events. 

Pietro Canetta, MD, MS:
To be clear, the use of biologics to treat IgAN is strictly experimental. This would apply, in particular, to the assortment of agents in development that are targeting the proliferation-inducing ligand (APRIL) and B-cell–activating factor (BAFF) system. These are mostly monoclonal antibodies or fusion proteins that are delivered by IV or SC injection. In addition, some of these agents are or soon will be in active phase III trials. I am very hopeful that one or more will be successful based on promising results from their respective phase I/II studies. These drugs impair B-cell activation and lower immunoglobulin levels; thus, prolonged use raises concerns about their cumulative risk for infections. Available data for these agents in patients with IgAN have not shown a particularly elevated rate of infections, but you can be sure this question will be scrutinized in clinical trials by both the pharmaceutical manufacturer and respective regulatory agencies. Other adverse events include infusion reactions, particularly for injections, which were mostly mild.

Additional biologics are being developed for IgAN that target other parts of the immune system, including lymphocytes (eg, anti-CD38) or the complement system. Adverse events here depend on the specific target, as well as the formulation of the drug (ie, antibody vs small molecule vs interfering RNA). Broadly speaking, the main adverse event to be concerned about here is infection. For complement-system–targeting agents, a particularly important concern is the risk of encapsulated bacteria. Therefore, the use of such therapies typically requires specific vaccinations and/or prophylactic antibiotics, which is similar to how one would use anti-C5 agents for complement-mediated hemolytic uremic syndrome.

Should patients’ IgAN dosage regimen ever be titrated up or down? If yes, how should one approach this? 

Richard Lafayette, MD, FACP:
There is a need to maximize RAS inhibitors to a well-tolerated level, as evidence suggests that greater degrees of proteinuria reduction and renal protection are seen with higher doses. For Nefecon, only the approved dose has been studied, and it requires a short taper (2 weeks at half the dose) to ensure there are no steroid withdrawal issues. For biologics, once approved they likely will be used at fixed doses. Lastly, endothelin blockers will have an optimal “full” dose. But if patients’ blood pressure is too high and/or their estimated glomerular filtration rate falls too much, a reduced dosage may be reasonable. 

Pietro Canetta, MD, MS:
Dose titration depends on the therapy in question. For angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and sodium-glucose cotransporter 2 inhibitors, I titrate up to the maximum dose that is tolerable. For sparsentan, the starting dose is 200 mg daily for 2 weeks, after which it should be increased to 400 mg daily if tolerated. The tolerability question here relates to hypotension or hyperkalemia from the angiotensin-blocking effect of sparsentan. For targeted-release budesonide, the dose is fixed at 16 mg daily, but it is recommended to reduce to 8 mg daily for 2 weeks prior to discontinuation because of potential steroid-withdrawal effects.  

How can healthcare professionals (HCPs) help patients overcome the costs of these medications?

Pietro Canetta, MD, MS:
This is an important and thorny question. In addition, it is one that requires collaboration from many: patients, HCPs, government regulators, the pharmaceutical industry, and payers. It is not fair to ask individual HCPs to weigh the costs of each prescription and patients’ goals for their health vs their ability to afford their prescriptions. HCPs should be able to advocate for their patient to a reluctant payer, familiarize themselves with the options available for those who cannot afford their prescription costs (eg, patient assistance programs or co-pay assistance programs), and understand the magnitude of benefit of the specific prescription (compared with its alternatives) to effectively counsel patients about their out-of-pocket costs and available resources to help.

As for the larger issue of the systemic costs to the healthcare system, drug development is a risky and expensive process. The companies who fund these projects need to recoup their investments and continue to build sufficient motivation to innovate further. The government and payers ought to negotiate fair prices better. Patient groups and professional societies can and should advocate for equitable and affordable access to care. Broadly speaking, I think this is a “good” problem to have because it means there are new treatment options for our patients (as opposed to years when there were no significant advances in therapy). Finally, one important benefit of having so many agents in development is that once approved, there should be competition that will bring down prices and increase accessibility.

Your Thoughts?
How often are you advocating to a payer on your patients’ behalf so they can access new and emerging therapies in IgAN? Answer the polling question and get involved in the discussion by posting a comment.

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How often are you advocating to a payer on your patients’ behalf so they can access new and emerging therapies in IgAN?

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