usually managed with an initial induction therapy
using methylprednisolone, cyclophosphamide,
mycophenolate mofetil, or combinations
thereof. 14–16 In lupus nephritis, the low-dose regimen
proposed in the Euro-Lupus Nephritis Trial 17 is the
most commonly used cyclophosphamide regimen,
and comprises six pulses of 0.5g cyclophosphamide,
one every second week for a total of three months,
followed by maintenance therapy with
azathioprine. Together with mycophenolate mofetil,
this regimen has replaced the initial high dose NIH
cyclophosphamide protocol, 18–20 mainly because of
severe infections and toxicity concerns, for example,
associations with premature gonadal failure. 21 In
patients with nephritis who have not responded to
this management, the anti-CD20 monoclonal
antibody rituximab may be an alternative. 22
Calcineurin inhibitors have received growing
attention as potential therapeutic agents in SLE,
especially in lupus nephritis. 23 Low doses of
tacrolimus are effective and well tolerated in
patients with renal SLE who have failed treatment
with cyclophosphamide, 24 and an open-label
prospective study showed non-inferiority of
tacrolimus as an induction therapy of active
biopsy-proven nephritis compared with
mycophenolate mofetil and cyclophosphamide. 25
Later, a meta-analysis of nine studies
demonstrated that tacrolimus was superior to
cyclophosphamide but not to mycophenolate
mofetil in inducing complete renal remission
in lupus nephritis. 26 Results from recent studies
of voclosporine are awaited.
In recent years, more targeted therapies have
been investigated, and biological agents have
been used either following approval or as off-label
therapies. Future strategies that may prove
promising include small molecules modifying
intracellular signal pathways, for example,
through targeting Lyn, Syk, PI3Ks and Btk. The
proteasome inhibitor bortezomib, approved for
the treatment of multiple myeloma, was recently
shown to improve the disease activity and reduce
the numbers of peripheral blood and bone
marrow plasma cells in twelve refractory SLE
patients. 27 Lupuzor, also known as P140 peptide
and IPP-201101, is a 21-mer linear peptide
originating from the small nuclear
ribonucleoprotein U1-70K, phosphorylated at
the Ser140 position. The mechanism of action
of lupuzor is not fully elucidated, but studies
in