Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

Abstract

This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%), gastrointestinal AEs (3.2–66.7%), and amenorrhea and/or ovarian complications (0–71%). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp.) or AZA (17–77% versus 11–29%, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp.) or AZA (32–71% versus 8–18%, resp.). Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

Interleukin‐6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus

“…IL‐6 has been proposed to play a major a role in the development of SLE and especially in patients with lupus nephritis, IL‐6 levels were found to be increased . We have shown in a previous study that mice with loss of epidermal JunB mice develop a SLE phenotype linked to increased epidermal IL‐6 secretion .…”

“…Untreated or insufficiently treated SLE might result in severe complications or death of patients. Today's state‐of‐the art therapy such as livelong immunosuppression, antimalarials or belimumab might not prevent organ damage, and it is associated with problematic side effects . Therefore, a strong need for novel disease‐specific therapies of SLE exists.…”

CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis – from bench to bedside?

“…Immunosuppressive therapies as cyclophosphamide, glucocorticoids, azathioprine, mycophenolate mofetil (MMF) and biologicals have improved the disease outcome in the last decades. However, it remains difficult to achieve complete remission with these treatment strategies, and side effects of this medication are common [26,27]. As it is known that an early diagnosis and a contemporary treatment of the disease leads to an improved outcome of SLE patients, biomarkers that enable an early detection of SLE and LN in particular are of great clinical interest.…”

Long‐Term Safety and Efficacy of Belimumab in Patients With Systemic Lupus Erythematosus

“…Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects a number of organ systems (1) and causes a marked impairment in quality of life (QoL) (2,3). Active disease (4,5) and medication toxicities contribute to the accrual of long-term organ damage (6)(7)(8). Corticosteroids and immunosuppressant drugs have demonstrated clinical benefits (9); however, concerns remain about the safety of their long-term use (6)(7)(8).…”