Long-lived, AB-secreting plasma cells have been involved in the pathogenesis of SLE, but they are NOT responsive to the standard im/m. (immunosuppress
REFRACTORY LUPUS
Targeting CD38 in patients with refractory systemic lupus erythematosus (SLE) (Oct 2020).
Long-lived, AB-secreting plasma cells have been involved in the pathogenesis of SLE, but they are NOT responsive to the standard im/m. (immunosuppressive) therapy. The administration of daratumumab, a CD38-directed monoclonal AB depleting plasma cell, was received by 2 ptns with life-threatening, therapy-refractory sequelae of SLE (e.g., lupus nephritis, pericarditis, & autoimmune Haemolytic anemia). Both cases, however, showed daratumumab-induced favourable clinical & serologic response with no rise in the risk of opportunistic infection. Despite their promising therapeutic impact, these observations need more confirmation via larger clinical studies to recognize whether daratumumab can provide a participation in the ttt of refractory lupus cases.
Recent agents in clinical trials: Novel therapeutic agents on trial include: B-targeted agents (e.g., atacicept & blisibimod), anti-Jak/stat or tyrosine kinase (e.g., baricitinib), ustekinumab, IL-6 receptor, interferon-a inhibition e.g., anifrolumab, low-dose IL-2, obinutuzumab, voclosporin, daratumumab (see above), & T-cell co-stimulator blocker (abatacept). More details about current trials in the US can be found at www.clinicaltrials.gov/.
SLE may show a variable clinical behaviour that range from benign disease to the vigorous progressive illness with fulminant systemic organ failure & death. The 5-y survival rate of SLE has been dramatically rising since mid-20th century, from 40 % in 1950 to > 90 % in 1980. This improvement in ptn survival can be attributed to many factors including better disease recognition with more sensitive diagnostic tools, earlier Dgx & ttt, the inclusion of milder cases, more judicious therapy, and better ttt of SLE sequelae. Despite these advancements, ptns with SLE still showing high MR ranging from 2-5 times higher than other general populations. Based on MR data from the US Centres for Dis. Control & Prevention (CDC) from 2000-2015, SLE has been ranked within the top 20 leading causes of death in ladies between 5-64. Another large study in US, SLE MR was higher in: (1) women, (2) African Americans, & (3) Southern residents.
Prognostic factors: Poor prognostic factors in SLE may include:
1) HT.
2) Male gender
3) Younger age
4) Older age at presentation
5) Low socio-economic status
6) Type of renal disease (esp. diffuse proliferative GN).
7) Black race (reflecting the low socioeconomic status).
8) The finding of anti-phospholipid AB.
9) Associated anti-phospholipid AB syndrome.
10) Higher parameters of the overall lupus activity.
Causes of death: main causes of death in the 1st few ys of disease are active illness (e.g., CNS & kidney disease) or infection due to im/m., on the other hand, late causes of death may include complications of SLE (e.g., ESRD), ttt complications, & CVS disease. Risk of death related to CVS disease; infection, & kidney disease were significantly higher. MR due to cancer was has been increased, while ptns with renal disorder were found to be the highest MR risks.
Morbidity: Despite the reduced risk of premature mortality, ptns are at risk of significant morbidity due both to (1) active disease & (2) SE of medications e.g., steroids & cytotoxic agents. Steroids-induced avascular necrosis hips & knees, osteoporosis, & cognitive malfunction have become particularly important problems as patients live longer with their illness with a concomitant increase in total glucocorticoid exposure. Factors leading to short delay between disease onset & organ failure may include:
1) Hispanic ethnicity
2) Higher disease activity
3) PH of thrombo-embolism.
4) Steroid therapy of < 10 mg/d.
Steroid use of prednisone ≥10 mg/d has related to a longer period from disease onset to organ failure, however, long-term steroid administration may be related to a higher risk of more sequelae. However, relationship between the magnitude of steroid dosage and the evolution of organ failure is to be determined, still there’re conflicting findings.
Is cancer risk increasing? Despite the overall higher risk of death related to malignancy does not seem to be elevated among SLE ptns, the risk of death related to malignancy, e.g., non-Hodgkin lymphoma, is significantly higher among SLE ptns if compared to general cohorts. This type of cancer in SLE ptns is currently with aggressive course, diffuse large B-cell lymphoma in particular. Common locations of cancer may include vulva, cervical region, lungs, thyroid & may be the liver.
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