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

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.

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PSY2 Adverse Event Burden, Resource Use and Costs Associated With Immunosuppressant Therapy for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

Value in Health ◽

10.1016/j.jval.2012.03.536 ◽

2012 ◽

Vol 15 (4) ◽

pp. A98

Author(s):

A. Shaul ◽

T. Pokora ◽

C. Paramore ◽

L.S. Cragin ◽

A. Weinstein ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Adverse Event ◽

Literature Review ◽

Systematic Literature Review ◽

Resource Use ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Immunosuppressant Therapy

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Real-World Experience of Safety of Mycophenolate Mofetil in 119 Japanese Patients with Systemic Lupus Erythematosus: A Retrospective Single-Center Study

BioMed Research International ◽

10.1155/2021/8630596 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Yoshiyuki Abe ◽

Kurisu Tada ◽

Ken Yamaji ◽

Naoto Tamura

Keyword(s):

Systemic Lupus Erythematosus ◽

Mycophenolate Mofetil ◽

Adverse Events ◽

Lupus Erythematosus ◽

Japanese Patients ◽

Discontinuation Rate ◽

Single Center ◽

Systemic Lupus ◽

Single Center Study ◽

Center Study

Objectives. Mycophenolate mofetil (MMF) is the standard treatment for lupus nephritis. In Japan, it was approved for lupus nephritis in 2015. We investigated its real-world safety and effectiveness in Japanese patients with systemic lupus erythematosus (SLE). Methods. We analyzed the continuation rate, adverse events, and reasons for discontinuation of MMF in Japanese patients with SLE in a retrospective single-center study. We included 119 patients who received MMF from 31 July 2015 to 31 May 2019. To compare demographic and clinical characteristics between groups, the Mann–Whitney U -test was used for nonnormally distributed variables. Categorical variables were compared using Fisher’s exact test. Kaplan–Meier curves were plotted for the discontinuation rate of MMF. Results. Patients consisted of 18 males and 101 females. Thirty-five patients discontinued MMF. The cumulative discontinuation rate was 42.4%. Twenty-nine patients discontinued MMF due to adverse events, and six patients discontinued MMF due to remission of SLE or desire for childbearing. At the time of the last observation, the lupus low disease activity state achievement rate was significantly lower in patients who experienced adverse events than those who did not (64% vs. 35%, P = 0.009 ). We examined the concentration of mycophenolate acid (trough level) in stored frozen serum in 11 patients. Two patients had irreversible complications due to viral meningitis; their trough mycophenolate acid concentrations were 8.3 and 6.3 μg/mL, respectively. Conclusions. Although MMF may be effective in Japanese patients with SLE, physicians should pay attention to infections in patients with high mycophenolate acid concentrations.

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Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups

Nature Communications ◽

10.1038/s41467-021-21049-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yong-Fei Wang ◽

Yan Zhang ◽

Zhiming Lin ◽

Huoru Zhang ◽

Ting-You Wang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Genome Wide Association Study ◽

Age Of Onset ◽

Treatment Options ◽

Human Leukocyte ◽

Risk Scores ◽

Systemic Lupus ◽

Disease Manifestation ◽

A Genome

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

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POS0685 MYCOPHENOLATE MOFETIL IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: FIVE-YEARS DRUG SURVIVAL IN RENAL AND NON-RENAL INVOLVEMENT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.925 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 588.2-588

Author(s):

G. Olivieri ◽

F. Ceccarelli ◽

F. Natalucci ◽

F. R. Spinelli ◽

C. Alessandri ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Mycophenolate Mofetil ◽

Disease Activity ◽

Lupus Erythematosus ◽

Treatment Duration ◽

Retention Rate ◽

Renal Involvement ◽

Joint Involvement ◽

Systemic Lupus ◽

Median Treatment

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared

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AB0818 ADVERSE EVENTS UNDER B-CELL DIRECTED THERAPIES IN A LARGE SINGLE-CENTER COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS, SYSTEMIC LUPUS ERYTHEMATOSUS, ANCA-ASSOCIATED VASCULITIS AND RENAL DISEASES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1214 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1433.1-1433

Author(s):

J. G. Rademacher ◽

V. Korendovych ◽

P. Korsten

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Adverse Events ◽

B Cell ◽

Clinical Data ◽

Lupus Erythematosus ◽

Infectious Complications ◽

Single Center ◽

Systemic Lupus ◽

Anca Associated Vasculitis

Background:The anti-CD20 antibody rituximab (RTX) is approved for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV). In addition, RTX is used in a wide range of autoimmune diseases. Belimumab (BEL) is an anti-BAFF antibody approved for the treatment of non-renal systemic lupus erythematosus (SLE) in Europe. These agents are generally well-tolerated but severe adverse events (AEs) can occur. The frequency of and factors associated with AEs are currently unknown.Objectives:To identify adverse events with the use of B-cell directed therapies in a large population of RA, AAV, and SLE.Methods:This is a single-center retrospective cohort study using routine clinical data over a ten-year period (2010-2020). We recorded epidemiological and clinical data of patients receiving either BEL or RTX. Data included age, gender, type of disease, number and efficacy of infusions, patient-years and concomitant treatment. Patient records were screened for AEs, such as infections, anaphylaxis, occurrence of malignant disease, laboratory abnormalities and immunoglobulin (Ig) deficiency. Between group comparisons were performed.Results:Database screening yielded 445 patients treated with RTX and 23 with BEL. After exclusion of patients with incomplete data, 425 RTX and 23 BEL patients were analyzed.Our preliminary analysis of a sample of 60 of these 448 patients (184 patient-years) resulted in 43 patients (72%) with RA, 8 patients with AAV (13%), 5 patients with a renal disease, and 4 patients with mixed connective tissue disease, as well 23 SLE patients. 46 (77%) were female. In RA, a median of 13 treatments of 1000 mg were administered, corresponding to 3.37 patient-years per patient. Primary non-response occurred in 2 patients, secondary non-response in 13 patients. For AAV, a median of 8.4 treatments were given (3.3 patient-years), no treatment failure was detected. SLE patients received a median of 15 treatments.15 patients had infectious complications during treatment, 11 needed treatment. Herpes zoster infection occurred in 3 patients with RA. Three of the 8 patients with AAV had an infection requiring treatment. In SLE patients, only 2 developed infectious complications, and no Ig-deficiency occurred.Lymphopenia was the most common laboratory abnormality detected in 25 patients with RTX, 19 of whom had RA. Ig deficiency was common in RA, affecting 30% of patients. Deficiency of IgM and IgG was recognized in 5 patients each; 1 patient had low levels IgA.Neither the maintenance prednisolone dosage nor Ig deficiency were associated with risk for infection. However, lymphopenia appeared to be associated with risk for infection.Conclusion:Our preliminary data observe a 184 patient-year period. RTX and BEL were generally associated with few AEs. RA patients frequently had laboratory abnormalities (lymphopenia, Ig-deficiency) which did not necessarily translate to clinical events. Infections were more common in AAV, BEL was the best tolerated B-cell directed agent. Overall, our data are reassuring, but we suggest a more careful vigilance in AAV patients.Disclosure of Interests:Jan-Gerd Rademacher: None declared, Viktor Korendovych: None declared, PETER KORSTEN Speakers bureau: Abbvie, Sanofi Aventis, GSK, Chugai, Boehringer-Ingelheim, Novartis, Consultant of: Lilly, Gilead, Boehringer-Ingelheim, Novartis, GSK, Grant/research support from: GSK

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