Eular Congress News - EULAR 2020 Report

As many as 40% of patients with systemic lupus erythematosus (SLE) develop kidney disease, which remains a major cause ofmorbidity, according to Dr. Antonis Fanouriakis of Attikon University Hospital,Athens, who presented new guidelineson the treatment of lupus nephritis fromEULAR and the European Renal Association–European Dialysis and TransplantAssociation (ERA-EDTA).

The researchers followed the EULARstandardised operating procedures fortreatment recommendations, which werepublished in Annals of the RheumaticDiseases. They used Delphi-based methodology to develop 15 questions for a systematic literature review on which to basethe recommendations.

Key changes from the 2012 recommendations include ones for treatment targets,use of glucocorticoids and calcineurininhibitors, and management of end-stagekidney disease (ESKD).

The target of therapy is completeresponse proteinuria less than 0.5-0.7g/24 hours with near-normal glomerularfiltration rate by 12 months. This can beextended in patients with baseline nephrotic-range proteinuria.

The recommendations also call for long-term treatment with hydroxychloroquinewith regular ophthalmologic monitoring.

For patients with active proliferative lupusnephritis, the recommendations call for initialtreatment with mycophenolate mofetil ( 2-3g/day, or mycophenolic acid at equivalentdose) or low-dose intravenous cyclophosphamide (500 mg x 6 biweekly doses), bothcombined with glucocorticoids (pulses ofintravenous methylprednisolone, then oralprednisone 0.3-0.5 mg/kg per day).

Alternative treatments for patients with
nephrotic-range proteinuria and adverse
prognostic factors include a combination
of mycophenolate mofetil and calcineurin
inhibitors (especially tacrolimus), as well
as high-dose cyclophosphamide.
The recommendations advise on subse-
quent long-term maintenance treatment
with mycophenolate mofetil or azathio-
prine with no or
low-dose glucocor-
ticoids (less than 7. 5
mg/day).
“The choice of
agent depends
on the initial regi-
men and plans for
pregnancy,” the
guidelines commit-
tee said. “In non-
responding disease, switch of induction
regimens or rituximab are recommended.

In pure membranous [lupus nephritis] with
nephrotic-range proteinuria or proteinuria
greater than 1 g/24 h despite renin-an-
giotensin-aldosterone blockade, [myco-
phenolate mofetil] in combination with
glucocorticoids is preferred.”
Patients should be regularly assessed
for both renal and extra-renal disease
activity, with repeat kidney biopsy con-
sidered in cases of incomplete response
or nephritic flares, the authors said. Addi-
tionally, comorbidities should be managed
throughout a patient’s lifespan.

For patients with ESKD, the recommendations favor transplantation as thepreferred kidney replacement option, “withimmunosuppression guided by transplantprotocols and/or extra-renal manifestations,” the committee said.

“Since the publication of the first set of
joint EULAR/ERA-EDTA recommendations
in 2012, new evidence has emerged in
lupus nephritis, including the use of calci-
neurin inhibitors and ‘multitarget’ therapy,
disease monitoring and treatment targets,”
Dr. Fanouriakis said in an interview. “To
this end, it was deemed appropriate to up-
date these recommendations at this time.”
Dr. Fanouriakis noted that the COVID- 19
pandemic has imposed “unprecedented
changes” in the practice of medicine.

“Lupus nephritis is a condition whichrequires a multidisciplinary approach involving physicians of different specialties,while at the same time these patientsmay carry an increased risk for infections,owing both to their disease and medications,” he said. “To this end, face-to-faceexaminations for diagnosis, treatment,and regular patient monitoring should beperformed in a protected setting; alternatively, if telemedicine services are to beapplied, this should try to involve differentmedical disciplines,” including rheumatology and nephrology.

The take-home message for cliniciansabout the recommendations is that “optimal outcomes in lupus nephritis aremore a matter of a long-term therapeuticstrategy, rather than individual drugs,” Dr.Fanouriakis explained. “An early responsein proteinuria (within 12 months) is thebest prognostic factor for a favourableoutcome; nevertheless complete responsemay require more time in patients withsignificant baseline proteinuria.

“A repeat kidney biopsy should beconsidered prior to labeling a patient as‘refractory’ or in case of nephritic flares,”he said.

The next steps for research in lupusnephritis management include “aspectsof diagnosis and patient stratification towards personalised treatment, prognosticbiomarkers, novel synthetic and biologictreatments, as well as optimisation of clinical trial design,” Dr. Fanouriakis noted.