Glucocorticoids have rapid and powerful anti-inflammatory and immunosuppressive effects , 12 and are used for most SLE manifestations , from mild cutaneous disease to life-threatening conditions , often in combination with other drugs . Pulse methylprednisolone therapy is commonly used during severe exacerbations to induce remission , followed by high doses of oral corticosteroids with a gradual taper . Low-dose oral corticosteroids are used in the vast majority of SLE patients as a long-term remission maintenance therapy . Fortunately , the glucocorticoid-induced harm has received increasing recognition in recent years . Apart from complications , recent indications of harmful effects of glucocorticoids on SLE itself have contributed to a scepticism towards the acceptance of long-term use , and a need for a paradigm shift has emerged . 13 Moderate to severe flares in major organs are
The management of SLE and the development of new therapies have been challenging because of the prominent heterogeneity of the disease in clinical presentation and underlying immunopathology , as well as its unpredictable course 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 lupus-prone mice have shown promising immunomodulatory effects , 28 – 33 and a Phase IIb trial evaluating 149 SLE patients documented greater response rates in patients receiving lupuzor than in patients receiving placebo . 34
Biologics in SLE Biologic agents have been the focus of research towards the development of modern therapies . Due to its important role in B cell homeostasis , BAFF has been of central interest as a target molecule .
Belimumab is the first drug to be licensed for use in SLE in more than 50 years , and the first biologic agent approved for the disease . The efficacy of belimumab in reducing SLE activity has been shown in Phase III randomised placebo-controlled clinical trials . 35 , 36 Belimumab is a recombinant human IgG1-λ monoclonal antibody that specifically binds to the soluble
19 HHE 2018 | hospitalhealthcare . com