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Investigators conducted what's believed to be the largest prospective observational studies of response to changing treatment regimens in patients with lupus nephritis who do not respond to initial, first-line therapy.
Approximately two-thirds of patients with refractory lupus nephritis (RLN) responded to a change in immunosuppression treatment while a significant minority showed no response, in a large prospective study of treatment outcomes.
Liza Rajasekhar, MD, Associate Professor, Nizam’s Institute of Medical Sciences, Hyderabad, India and colleagues point out that lupus nephritis is present in approximately one-third of patients at diagnosis of systemic lupus erythematosus (SLE).
“Progression to end-stage renal disease is a dreaded outcome,” Rajasekhar and colleagues emphasized.
The investigators undertook what they describe as among the largestprospective observational studies of response to changing treatment regimens in patients with lupus nephritis who do not respond to initial, first-line therapy.
They enrolled 48 patients consecutively admitted between August 2018 to January 2019 for lupus nephritis who had either not improved within 3 months of diagnosis, had not achieved partial renal response at 6 months, or had not achieved complete renal response after 2 years of treatment.The median duration of SLE was 3 years (range, 2-6 years).
“Since it is not easy to conduct a randomized controlled trial in this group of patients, we believe that this study presenting such data in 48 patients, followed prospectively with well documented details of therapy and outcome, will contribute to evidence which will guide therapy in initial non-responders,” Rajasekhar and colleagues explained.
Lupus nephritis was defined per American College of Rheumatology (ACR) criteria, with complete renal response marked by single “spot” urine protein:creatinine ratio (UPCR) <50mg/mmol (equivalent to proteinuria <0.5g/24h) and normal or near-normal (within 10%) glomerular filtration rate (GFR).
Partial renal response corresponded to ≥50% reduction in proteinuria to sub-nephrotic levels and normal or near-normal GFR.Lack of improvement, categorized as no renal response, was marked by no reduction in proteinuria or a deterioration of GFR.
Initial treatment strategies for RLN involved switching to another first-line drug, such as mycophenolic acid (MPA) from cyclophosphamide (CYC), and vice versa. Alternative approaches used at the discretion of the treating physicians included switching to tacrolimus, rituximab, or combination therapy such as MPA and tacrolimus. All patients received maintenance doses of oral corticosteroids, hydroxychloroquine, calcium/vitamin D, and ACE inhibitors. Steroid dose was not increased during switching of treatment.
Follow-up occurred during a flare and every 3 months, with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and notations on response to treatment and adverse events. The median follow-up period was 15 months (range, 12-27 months).
Rajasekhar and colleagues reported that 28 had complete renal response, 9 had partial response and 8 showed no response to a switch in an immunosuppressive agent. There were 3 deaths, all related to infection.There was no significant difference in treatment outcome and time to attain response associated with a particular immunosuppressive agent or sequence of agents.
None of the measured variables, including duration of SLE or nephritis, baseline SLEDAI score, leukopenia, hypertension, predicted renal response.
The investigators noted that the combination of tacrolimus and MPA produced a relatively high global response rate, consistent with previous reports of complete and partial response in 57-95%.There were no responders to tacrolimus as monotherapy, however. Approximately half of patients responded to MPA as a single agent, as did half of those receiving cyclophosphamide per NIH protocol and half on regimens which included rituximab.
“Numerically, best responses were seen using MPA and tacrolimus combination while switching immunosuppressive agents in any sequence proved effective in almost half the patients,” Rajasekhar and colleagues reported.
The study, “Treatment Outcomes in Refractory Lupus Nephritis: Data from an Observational Study," was posted as a preprint in Research Square.