Mycophenolate mofetil is an immunosuppressant commonly used to treat systemic lupus erythematosus (SLE) and lupus nephritis. It is a known teratogen associated with significant toxicities, including ...an increased risk of infections and malignancies. Mycophenolate mofetil withdrawal is desirable once disease quiescence is reached, but the timing of when to do so and whether it provides a benefit has not been well-studied. We aimed to determine the effects of mycophenolate mofetil withdrawal on the risk of clinically significant disease reactivation in patients with quiescent SLE on long-term mycophenolate mofetil therapy.
This multicenter, open-label, randomised trial was conducted in 19 centres in the USA. Eligible patients were aged between 18 and 70 years old, met the American College of Rheumatology (ACR) 1997 SLE criteria, and had a clinical SLEDAI score of less than 4 at screening. Mycophenolate mofetil therapy was required to be stable or decreasing for 2 years or more if initiated for renal indications, or for 1 year or more for non-renal indications. Participants were randomly allocated in a 1:1 ratio to a withdrawal group, who tapered off mycophenolate mofetil over 12 weeks, or a maintenance group who maintained their baseline dose (1-3g per day) for 60 weeks. Adaptive random allocation ensured groups were balanced for study site, renal versus non-renal disease, and baseline mycophenolate mofetil dose (≥2 g per day vs <2 g per day). Clinically significant disease reactivation by week 60 following random allocation, requiring increased doses or new immunosuppressive therapy was the primary endpoint, in the modified intention-to-treat population (all randomly allocated participants who began study-provided mycophenolate mofetil). Non-inferiority was evaluated using an estimation-based approach. The trial was registered at ClinicalTrials.gov (NCT01946880) and is completed.
Between Nov 6, 2013, and April 27, 2018, 123 participants were screened, of whom 102 were randomly allocated to the maintenance group (n=50) or the withdrawal group (n=52). Of the 100 participants included in the modified intention-to-treat analysis (49 maintenance, 51 withdrawal), 84 (84%) were women, 16 (16%) were men, 40 (40%) were White, 41 (41%) were Black, and 76 (76%) had a history of lupus nephritis. The average age was 42 (SD 12·7). By week 60, nine (18%) of 51 participants in the withdrawal group had clinically significant disease reactivation, compared to five (10%) of 49 participants in the maintenance group. The risk of clinically significant disease reactivation was 11% (95% CI 5-24) in the maintenance group and 18% (10-32) in the withdrawal group. The estimated increase in the risk of clinically significant disease reactivation with mycophenolate mofetil withdrawal was 7% (one-sided upper 85% confidence limit 15%). Similar rates of adverse events were observed in the maintenance group (45 90% of 50 participants) and the withdrawal group (46 88% of 52 participants). Infections were more frequent in the mycophenolate mofetil maintenance group (32 64%) compared with the withdrawal group (24 46%).
Mycophenolate mofetil withdrawal is not significantly inferior to mycophenolate mofetil maintenance. Estimates for the rates of disease reactivation and increases in risk with withdrawal can assist clinicians in making informed decisions on withdrawing mycophenolate mofetil in patients with stable SLE.
The National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Patients naïve to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and to the Ankylosing Spondylitis Disease Activity Score (ASDAS) have voiced confusion in our clinics over the use of ...the term "AS" in these instruments. It is unknown whether these tools may be applied to other related forms of spondyloarthritis (SpA). The Bath Ankylosing Spondylitis Functional Index (BASFI) questionnaire also requires more definitive validation. We 1) validated the BASFI against a standard definition of disability; and 2) validated slightly modified versions of the BASDAI and ASDAS questionnaires that replace references to "AS" with the term "inflammatory arthritis" for use in non-AS SpA.
Adult patients with SpA enrolled in the Veterans Affairs Program to Understand the Longterm outcomes in Spondylo-ARthritis (PULSAR) completed the BASFI, BASDAI, ASDAS and altered versions of the BASDAI (PULSAR-modified Bath Disease Activity Index PuBaDAI) and ASDAS (PULSAR-modified Ankylosing Spondylitis Disease Activity Score PuASDAS). Spearman correlations and logistic regression were used to analyse the scores.
The correlation between BASDAI and PuBaDAI and between ASDAS and PuASDAS scores was high (Spearman's rho=0.92, p<0.001 and Spearman's rho=0.85, p<0.001, respectively). The test-retest correlation of BASFI was also high (Spearman's rho=0.92, p<0.001). The BASFI (OR 1.67, 95% C.I. 1.12-2.47), ASDAS (OR 1.34, 95% C.I. 1.02-1.76) and PuASDAS (OR 1.62, 95% C.I. 1.07-2.49) predicted federally-determined disability.
Preliminary data suggest that BASDAI and ASDAS scores correlate well with modified forms of these questionnaires and that the ASDAS, PuASDAS and BASFI are associated with disability.
We performed a systematic review and meta-analysis to compare response rates (complete remission plus partial remission) for nonsteroid immunosuppressant therapy to steroid-only immunosuppressant ...therapy in patients with membranous lupus nephritis.
A literature review was conducted from June 25, 2010 by querying PubMed, MEDLINE, and EMBASE databases. Inclusion criteria were trials containing remission data on patients with confirmed pure class V (Va and Vb) membranous lupus nephritis. The primary analysis evaluates response rates for regimens that contain at least one nonsteroid immunosuppressant therapy and steroid-only immunosuppressant therapy. A proportion meta-analysis using a DerSimonian-Laird random-effects model was performed. Data are reported as pooled proportions in percentages with 95% confidence intervals. Significant heterogeneity and/or bias were compensated for by trial exclusion.
Twenty-four studies met inclusion criteria for meta-analysis, which yielded 34 groups of patients' data. Upon meta-analysis, the response rate for nonsteroid immunosuppressant therapy is higher than for steroids alone (81% 74%-87% vs 60% 39%-79%), even when compensating for significant heterogeneity and bias (76% 71%-81% versus 60% 39%-79%).
Nonsteroid immunosuppressant therapies in combination with steroids seem to be more effective than steroids alone for inducing partial or complete remission in patients with membranous lupus nephritis who have nephrotic proteinuria at baseline. This trial was not able to analyze adverse events, flares, relapses, or patient survival because of underreporting.
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Clinically diagnosed SLE cases consisting of predominantly African American females were studied for HLA trends and composition of regulatory T cells. Class II DRB1 typing revealed that ...30.8% of this population harbored at least one DRB1*1503 allelic haplotype. This 1503 subgroup exhibited a higher rate of serositis than did the non‐1503 subgroup. Flow cytometric analysis of lymphocyte populations did not demonstrate a difference among the CD4
+
/FoxP3
+
/CD25
+
staining regulatory T cells between the two subgroups. However, a significantly higher proportion of CD4
+
/FoxP3
+
/CD25
−
and CD4
+
/FoxP3
+
/CD25
variable
populations were found in the 1503 haplotype group than in to the non‐1503 group. This suggests a possible role for CD25 (IL‐2Rα) in the disease manifestations for this subgroup, and future studies will focus on other regulatory T cell surface markers, and whether activation, proliferation, and homeostasis of the immune reaction is compromised in the 1503 subgroup due to the decreased expression of CD25.
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