Discussion on latest management of lupus nephritis
(Part 5)
This corner will now discuss the subsequent treatment for lupus nephritis (LN) and non-responding/refractory disease.
Mycophenolat mofetil/mycophenolate acid (MMF/MPA) and azathioprine (AZA) are medicines of choice for subsequent immunosuppressive treatment related to the management of LN. This is, however, dependent on the patient’s response on the first phase of treatment.
The two (2) leading LN regimens are not different in terms of kidney flares, based in the data collected in the 10-year follow up of the Mycophenolate Mofetil Versus Azathioprine for Maintenance Therapy of Lupus Nephritis (MAINTAIN) trial. This is contrast to the Aspreva Lupus Management Study (ALMS) that manifested the vast superiority of MMF used as a drug for LN therapy.
Based on available pieces of evidence, increased relapses are observed when MMF/MPA is administered and followed with AZA. Experts recommend MMF/ MPA maintenance after the initial administration of the said set of drugs.
The introduction of cyclophosphamide (CY) may be followed by MMF/MPA or AZA; the latter is preferred if pregnancy is suspected or anticipated or cost of MMF is an issue.
Moreover, calcenurin inhibitors (CNI) may be used In class V LN at the lowest possible effective dose as long-term use of these medications may result in side effects that could impact the kidney health.
Most often, renal or kidney flares may occur within 5-6 years after the treatment’s introduction to the patient’s body.
In this regard, for a majority of patients, it is best to not discontinue with immunosuppression therapy prior to the said time.
The de-escalation of immunosuppression therapy should be considered for patients who have gained sustained and complete kidney response and the use of glucocorticoids (GC) must be tapered first. Gradual tapering of the administration of immunosuppression drugs are the most ideal before complete withdrawal.
In most cases, both longer duration of treatment and the longer duration of remission were linked with reduced risks of kidney flares in patients that discontinued their immunosuppression therapy, after 6 years.
To this end, the duration of immunosuppresive therapy should be individualized in accordance with timing and magnitude of the response, duration of flare-free maintenance, extra-renal systemic lupus erythematosus (SLE) activity and patient preferences.
In some instances, the disease becomes a non-responding/refactory one.
When there is a failure to achieve treatment goals that has been described earlier, this raises the possibility that the disease has become non-responding or refactory one.
In this event, proteinuria kinetics are important as decreasing proteinuria—to a level not yet meeting the ideal targets—may help justify to wait before switching therapy, especially in patients with nephrotic-range proteinuria at baseline, provided there is stability in kidney function.
Thorough assessment is important, including adherence to treatment with able measurement of drug levels, before declaring the disease a
nonresponding/refactory one.
All the first-line therapies, including MMF/MPA (2–3 g/day), CY and CNI (especially tacrolimus or TAC) as monotherapy or ‘multitarget’ therapy, are recommended in non-responding disease.
B-cell depleting therapies such as rituximab (RTX), although off-label, are also indicated either as monotherapy or as add-on therapy to MMF/MPA or CY.
It is predicted that the complete depletion of circulating B-cells to enter clinical remission at 76 weeks. This has recently been supported by a successful trial of obinutuzumab.
As a response to RTX, relapses are not uncommon, but occur after a variable length of time. Repeat doses can be considered to prevent or treat a relapse.
Although belimumab is not formally indicated for treating LN, post hoc analyses from randomized control trials (RCT) and observational studies suggest that when added to standard-of-care (including MMF), it may gradually reduce proteinuria and the risk for kidney flares.
The important thing is that positive results from phase III RCT of belimulab as an add-on LN therapy
The results from the phase III RCT of belimumab as an add-on therapy in LN have been released. But, the total results of the study are still being awaited.
The combination of RTX and belimumab has been used in refractory disease, in recent times.
High-dose intravenous immunoglobulin (2 g/kg) is something that can be considered when there are contraindications to increasing glucocorticoids or immunosuppressive drugs, which may include infection. On the other hand, plasma exchange is rarely indicated.
Next week we will be discussing adjunct treatment in patients suffering from LN.