Treatment options for refractory LN
Refractory LN is broadly defined as a failure to attain clinical remission with the standard treatment regimen based on unspecific immunosuppressants. It is associated with an increased risk of relapses, progression to end-stage renal disease, and mortality. The poor prognosis of this form of the disease requires aggressive treatment, regular reevaluations of patient response, and a flexible approach to therapeutic regimens. One possible option for these patients may be B-cell ablation with the chimeric anti-CD20 antibody rituximab, which appears to effectively induce remission when standard LN therapies fail (9, 10). Adverse events of rituximab treatment include infections and infusion reactions, but they are usually not serious (10).
Another important issue with refractory LN is its long-term prognosis, which is still elusive as there are scarce reports on the outcome for patients followed for 5 years or more, and in most cases the number of patients was small. Based on the currently available data, it seems that favorable factors for the good long-term outcome are the achievement of complete renal remission, the absence of nephritic flares, and their complete reversibility after therapy (11).
How to reduce corticosteroids without increasing the frequency of relapses?
It is undeniable fact that the outcome of LN has changed dramatically since the introduction of corticosteroid therapy, which efficaciously reduced mortality from this condition. However, event though corticosteroids remain the cornerstone in the treatment of LN, their administration is linked to many and severe side effects leading to organ damage. It seems that after adjustment for other variables, corticosteroid therapy, along with age, ethnicity, and hypertension, is an important predictor of organ deterioration (12, 13). And even though it may affect different systems, renal damage is the most important predictor of mortality within the damage index (14). These observations called for considerations of possible therapeutic alternatives to corticosteroids which would be equally efficient, but cause fewer side effects. The aforementioned belimumab again seems to respond to both challenges. In the longest study which assessed its effects, based on up to 13 years observation in patients included in clinical trials that allowed the registration belimumab for lupus therapy, this drug was well tolerated with no new safety concerns and provided good long-term disease control even with a progressive reduced dosage of corticosteroids (15). Results in real-life setting confirmed that in patients with active SLE and low damage at baseline, treatment with belimumab early in the disease lead to favorable outcomes in terms of a higher rate of remission and a lower rate of flares (16). A posthoc analysis of over 200 patients with LN included in the studies that allowed the registration of belimumab for lupus treatment, also showed that patients who received belimumab experienced fewer flares and needed lower corticosteroid doses compared to the placebo group (17). Even more so, a very recent study suggested that belimumab in some cases of LN may even allow the withdrawal of corticosteroids without any major adverse events (18).