Mandana Nikpour

Description:The Australian Scleroderma Cohort Study is supported by Janssen, Boehringer Ingelheim, Scleroderma Australia, Scleroderma Victoria, Arthritis Australia, Musculoskeletal Australia (muscle, bone and joint health), Australian Rheumatology Association, and St. Vincent's Hospital Melbourne Information Technology Department and Research Endowment Fund. Dr. Nikpour's work was supported by a National Health & Medical Research Council of Australia Investigator Grant (GNT1176538).

Description:IntroductionMaintenance of immunosuppressants (IST) is critical for sustaining remission in lupus nephritis (LN) patients. However, long-term use is associated with an increased risk of side effects such as infection. Yet, early IST withdrawal also poses a high risk of flare. This study aims to provide an overview of the impact of optimal IST withdrawal in patients with LN who have achieved remission.MethodWe conducted a systematic review of randomized controlled trials (RCTs) and observational studies regarding the discontinuation of IST in patients with proliferative LN who had been in remission for at least 1 year. Data from PubMed, ProQuest, and Web of Science were extracted on patient demographics, baseline characteristics, treatment regimens, and outcomes, including flare rates, renal function, and biopsy findings. The risk of bias was assessed using the Newcastle-Ottawa Scale and the JADAD Score.ResultsFive studies with 310 patients were included. The mean age of participants ranged from 26 to 38 years. Overall, flares following IST withdrawal occurred in an average of 28.7% of patients. Between the two groups (flare and no-flare), baseline serum creatinine was comparable, but baseline proteinuria and C3 & C4 levels were varied across studies. The duration of lupus before study entry was approximately 4-10 years, with a duration of complete remission of 12-59.5 months before IST withdrawal. Follow-up periods ranged from 24 to 215 months. The Biopsy Activity Index and Chronicity Index at baseline also showed variation but generally indicated a higher level of chronic damage in the flare group.DiscussionDiscontinuation of IST is feasible but may be associated with an increased risk of severe flares, often requiring reintroduction of induction therapy. Careful assessment and monitoring of both histologic and clinical activity are essential when evaluating remission and considering IST withdrawal, as a low activity index may guide safer withdrawal strategies.ConclusionIST withdrawal is feasible in patients with LN who have achieved remission, but careful monitoring is required due to the risk of relapse and potential progression of chronic kidney damage. Histological confirmation and predictive tools may support safer withdrawal decisions.

Description:To assess the frequency and determinants of immunosuppressant medication use in systemic sclerosis and changes in prescribing patterns over time. The Australian Scleroderma Cohort Study participants meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for systemic sclerosis with recorded treatment data were included. The Chi-square, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Multivariable logistic regression models were used to establish the determinants of the use of immunosuppressants. Of 2019 participants, 60% received immunosuppressants, including 81% of those with diffuse systemic sclerosis and 52% of those with limited systemic sclerosis (p < 0.001). Forty-six percent of patients received prednisolone and 40% disease-modifying anti-rheumatic drugs. Immunosuppressant use was more common in those with severe or inflammatory systemic sclerosis features, including interstitial lung disease, synovitis or myositis. Comparing prescribing patterns early in incident systemic sclerosis from 2007-2014 to 2015-2024, disease-modifying anti-rheumatic drug use increased (35% vs 56%, p < 0.001), while prednisolone use decreased (24% vs 17%, p = 0.046). Immunosuppressants were commenced earlier in incident systemic sclerosis in 2015-2024 versus 2007-2014 (1.8 (interquartile range = 1.0-3.2) vs 2.4 (interquartile range = 1.2-4.0) years, p = 0.011). In multivariable modelling, prednisolone use was associated with diffuse systemic sclerosis (odds ratio = 1.8, 95% confidence interval = 1.4-2.2, p < 0.001), interstitial lung disease (odds ratio = 2.1, 95% confidence interval = 1.7-2.5, p < 0.001), myositis (odds ratio = 2.7, 95% confidence interval = 1.8-4.0, p < 0.001), synovitis (odds ratio = 2.2, 95% confidence interval = 1.8-2.6, p < 0.001) and systemic sclerosis heart involvement (odds ratio = 1.4, 95% confidence interval = 1.0-2.0, p = 0.044). Disease-modifying anti-rheumatic drug exposure was associated with diffuse systemic sclerosis (odds ratio = 2.7, 95% confidence interval = 2.1-3.4, p < 0.001), interstitial lung disease (odds ratio = 2.2, 95% confidence interval = 1.7-2.7, p < 0.001), myositis (odds ratio = 3.6, 95% confidence interval = 2.4-5.5, p < 0.001) and synovitis (odds ratio = 4.2, 95% confidence interval = 3.5-5.2, p < 0.001) and inversely associated with age (odds ratio = 0.7, 95% confidence interval = 0.5-0.8, p < 0.01) and pulmonary arterial hypertension (odds ratio = 0.5, 95% confidence interval = 0.4-0.7, p < 0.001). In subgroups with diffuse systemic sclerosis and limited systemic sclerosis and different autoantibody profiles, findings were generally similar, with interstitial lung disease, synovitis and myositis tending to be associated with prednisolone and/or disease-modifying anti-rheumatic drug use, as was systemic sclerosis heart involvement in diffuse systemic sclerosis (p = 0.038). Immunosuppressant use is common in systemic sclerosis, with broadly similar determinants of usage among subtypes and autoantibody status. These real-world data suggest that disease-modifying anti-rheumatic drug use has increased, with earlier implementation of treatment, and a reduction in use of glucocorticoids.

Description:Objective: To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs). Methods: A post hoc analysis was carried out on five RCTs in active adult SLE: four with intravenous (BLISS-52, BLISS-76, BLISS-NEA, EMBRACE) and one with subcutaneous belimumab (BLISS-SC). The 52-week landmark assessments were analysed across trials. Treatment response was defined according to BICLA criteria (BILAG improvement; no worsening of disease activity based on BILAG and Systemic Lupus Erythematosus Disease Activity Index-2K; no deterioration in Physician's Global Assessment ≥0.3 (scale: 0-3); no treatment failure). Results: A total of 3086 patients received belimumab (n=1869) or placebo (n=1217). BICLA response frequencies at week 52 were greater with belimumab vs placebo in BLISS-52 (OR (95% CI): 1.49 (1.05-2.12); p=0.024), BLISS-NEA (1.62 (1.12-2.33); p=0.010) and BLISS-SC (1.89 (1.39-2.57); p<0.001). A highly significant difference was observed in the pooled population (1.47 (1.25-1.72); p<0.001; adjusted for trial variance). Belimumab yielded greater BICLA response frequencies than placebo irrespective of baseline glucocorticoid dose (>7.5 or ≤7.5 mg/day of a prednisone equivalent), in patients with baseline SLEDAI-2K≥10 and in patients with positive anti-double-stranded (ds)DNA and/or low C3/C4 levels at baseline. Belimumab combined with anti-malarials yielded greater frequency of BICLA response attainment. Conclusions: In this analysis of five RCTs evaluating belimumab in SLE, belimumab conferred superiority over placebo to yield BICLA response in the overall study population and in subgroups of patients with high global or serological activity at baseline. The benefit of belimumab was more prominent when combined with anti-malarials.

Description:Objective: Systemic sclerosis related interstitial lung disease (SSc-ILD) is a major cause of morbidity. We aimed to identify patients following similar trajectories of forced vital capacity (FVC) decline, examine their association with mortality and risk factors for FVC decline. Methods: This is a multicentre retrospective study of 444 SSc patients with ILD and ≤7-year disease duration. Patients were grouped based on similar FVC decline trajectories using semi-parametric modeling with latent class analysis. Survival was compared between the worst FVC trajectory group and the others. Logistic regression models with backwards selection were applied to identify predictors of FVC trajectory using baseline disease features. Results: Four FVC trajectory groups were identified. The most progressive trajectory declined by -2.18% per year and the other 3 trajectory groups were stable or progressed slowly. The most progressive group had a higher mortality rate than those with a stable/slow FVC trajectory (hazard ratio 2.95, 95%CI 1.74, 4.98). Baseline FVC (p< 0.001) and CRP elevation (p= 0.039) were associated the progressive trajectory. Baseline FVC ≤ 72% predicted the progressive trajectory with a sensitivity of 0.88 and specificity of 0.91. A lower baseline FVC was in turn associated with older age, Caucasian race, longer disease duration, ATA presence, and elevated CRP on exploratory analyses. Conclusions: Distinct FVC trajectories are associated with different survival outcomes and the most important predictor of a progressive FVC trajectory was existing ILD severity. More work is needed to assess the utility of imaging or paraclinical findings that can improve prediction of distinct FVC trajectories.