Efficacy and Safety of Nonbiologic Immunosuppressants in the Treatment of Nonrenal Systemic Lupus Erythematosus: A Systematic Review

Abstract

Objective. To analyze the efficacy and safety of nonbiologic immunosuppressants in the treatment of nonrenal systemic lupus erythematosus (SLE).Methods. We conducted a sensitive literature search in Medline, Embase, and the Cochrane Central Register of Controlled Trials up to October 2011. The selection criteria were studies including adult patients with SLE, a treatment intervention with nonbiologic immunosuppressants, a placebo or active comparator group, and outcome measures assessing efficacy and/or safety. Meta-analyses, systematic reviews, clinical trials, and cohort studies were included. The quality of each study was evaluated using Jadad's scale and the Oxford Levels of Evidence. Results. In total, 158 of the 2,827 initially found articles were selected for detailed review; 65 studies fulfilled the predetermined criteria. Overall, the studies were low quality, with only 11 randomized controlled trials (RCTs). Cyclophosphamide demonstrated efficacy for neuropsychiatric SLE, preventing relapses with an additional steroidsparing effect, although its use was associated with cumulative damage, development of cervical intraepithelial neoplasia, and ovarian failure. Other immunosuppressants (azathioprine, methotrexate, leflunomide, mycophenolate mofetil, and cyclosporin A) demonstrated efficacy in reducing nonrenal activity and flares with a steroid-sparing effect, although only on occasion in non-placebo-controlled RCTs of small numbers of patients. Conclusion. Several immunosuppressants demonstrated their safety and efficacy in nonrenal SLE. A specific drug for each particular manifestation cannot be recommended, although cyclophosphamide may be used in more severe cases, and methotrexate may be the first option in most cases of moderately active SLE. High-quality RCTs of larger numbers of patients are needed.

Good Response of Lupus Hepatitis to Mycophenolate Mofetil and Belimumab as of Lupus Exanthema to Rituximab: A Case Report

“…However, we could confirm an excellent response of this condition to MMF and belimumab, as previously published [17,18]. Additionally, we observed good response of joint pain to MMF in accordance with published data [23]. On the contrary, we could not confirm efficacy of a combination consisting of MMF, HCQ and belimumab in skin lesions, as published previously [18,19,24].…”

Systemic lupus erythematosus: An update for ophthalmologists

“…This is an area that has recently been reviewed elsewhere, and only trials from 2005 onwards have been discussed here 104 . Many of these trials are small, the patients are heterogeneous, and the outcome measures are highly variable and often not validated in clinical trial research.…”

Update on Biologic Therapies for Systemic Lupus Erythematosus

“…HCQ, for instance, can result in time-and dose-dependent retinal toxicity and visual loss [27]; CYC can induce hemorrhagic cystitis, ovarian failure, malignancy, and infections [20,22]; prolonged or high-dose GC therapy is associated with multiple side effects including weight gain, osteoporosis, hypertension, glucose intolerance, immunosuppression, myopathy, delayed wound healing, and behavioral changes [28,29]. On the one hand, the use of these medications, allied with better diagnostic and therapeutic strategies, led to an increase in the 5-year survival rate of SLE patients from about 50-70 % in the 1950s to over 90 % in the 1990s and later [7,30].…”

“…SLE which does not respond to the initial treatment, or which is controlled only by the prolonged administration of GCs in unacceptably high doses, may be treated with immunosuppressive (IS) agents such as methotrexate (MTX), azathioprine (AZA), and mycophenolate mofetil (MMF) [20,21]. SLE with neuropsychiatric manifestations may respond to intravenous (IV) infusions of cyclophosphamide (CYC) [21,22]. Severe lupus nephritis (LN) has been traditionally managed with a combination of GCs and high-dose CYC (six monthly IV pulses of 0.5-1.0 mg/m 2 of body surface area [BSA] for remission induction, followed by quarterly IV CYC as the maintenance therapy, i.e., the BNIH regimen^) [23].…”

“…Treatment of mild SLE (without major organ involvement) includes nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine (HCQ), and/or glucocorticoids (GCs) [20][21][22]. SLE which does not respond to the initial treatment, or which is controlled only by the prolonged administration of GCs in unacceptably high doses, may be treated with immunosuppressive (IS) agents such as methotrexate (MTX), azathioprine (AZA), and mycophenolate mofetil (MMF) [20,21].…”