Treat-to-target SLE strategy in 10 years: Discussion of current limitations and available options for implementation in real-world clinical practice

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

Introduction. CDK4/6 inhibitors in combination with endocrine therapy (ET) are the current standard of care for patients with HR+ HER2- advanced and metastatic breast cancer (eBC and mBC). Evidence of the clinical efficacy of CDK4/6 inhibitors has been obtained in several randomized clinical trials (RCTs), but data on their efficacy in real-world clinical practice (RCP) are contradictory. Objective. The aim of the ICEDORA study was to analyze clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC receiving CDK4/6 inhibitors in a real-world clinical practice in Moscow. Materials and methods. ICEDORA is a non-interventional retrospective study based on the analysis of data on patients receiving CDK 4/6 inhibitors in Moscow. Clinical characteristics and treatment details of all patients with HR+ HER2-breast cancer who received ribociclib, palbociclib, or abemaciclib from January 2020 to the end of December 2022 were extracted from primary medical records (outpatient charts and medical histories) by parsing. Overall survival (OS) was calculated from the date of breast cancer diagnosis until patient death using the Kaplan-Meier method, and differences between treatment groups were assessed using the log-rank test. Multivariate logistic regression and Cox proportional hazards models were built to exclude the influence of confounders and systematic errors. Results. The analysis included 2051 patients. 58.7 % received palbociclib, 34.7 % — ribociclib, 6.6 % — abemaciclib. The median age in the overall population was 58 years, but it was higher in the abemaciclib group (62 years). In 83.5 % of cases, Her2/neu was negative, the groups were homogeneous in this indicator. The level of estrogen receptors (ER) Ki-67 was significantly higher in the abemaciclib group. In the overall population, patients with primary metastatic breast cancer (stage IV) accounted for 42.1 %. The distribution of stages within each group was comparable. The groups differed significantly in the number of metastases due to a higher proportion of patients with one metastasis in the abemaciclib group (31.9 %) compared to the ribociclib (19.0 %) and palbociclib (16.6 %) groups, where the number of metastatic foci was more than one. Comorbidity was present in 90 % of patients. Differences in the baseline characteristics of patients receiving different drugs require caution when interpreting the study results. Conclusion. The ICEDORA study, which included patients taking CDK4/6 inhibitors in real-world clinical practice in Moscow, is one of the largest analyses of clinical and demographic characteristics, treatment regimens, and clinical outcomes in patients with HR+ HER2- mBC and mBC taking CDK4/6 inhibitors in real-life clinical practice in Russia. Comparative analysis of the efficacy of ribociclib, palbociclib, and abemaciclib in real-life clinical practice was not planned or conducted due to differences in the clinical and demographic characteristics of patients. Larger multicenter data withbalanced cohorts and long-term follow-up are needed.

Background: Disease activity metrics for systemic lupus erythematosus (SLE) are not widely used in real world clinical practice. Objectives: To assess the use and drivers of SLEDAI and BILAG index in real world clinical practice. Methods: A cross-sectional study of rheumatologists in the US and EU5. Data were collected from the Adelphi Real World 2010/2013/2015 Lupus Disease Specific Programmes (DSP). Physicians were asked to complete an attitudinal survey and patient record forms (PRFs) for the next 5 patients consulting with SLE; the same patients were asked to complete patient self-completion (PSC) forms describing how SLE affected them. PRFs collected data pertaining to the patient’s diagnosis, disease history, current clinical outcomes, treatment and management history. PSCs focused on similar data collection and included patient reported outcome measures (PROs) to assess the humanistic burden. 2015 DSP data was used to assess the profile of patients with a SLEDAI assessment were compared to those without a SLEDAI assessment, using Fisher’s Exact and Mann-Whitney tests. Similar analysis was also conducted for those with/without BILAG index assessments. 2013 & 2010 DSP datasets were merged, and multiple linear regression was used to assess drivers of SLEDAI and BILAG index utility, respectively. Results: Physicians provided 263 surveys, extracted from the 2015 DSP, indicating that 131 were aware of but did not use the BILAG index, and 92 of physicians were aware of but did not use the SLEDAI. Physicians provided 1376 record forms for SLE patients, extracted from the 2015 DSP; 71 (5.2%) had a BILAG index (1305, 94.8% had no BILAG index), and 373 (27.1%) had had a SLEDAI calculated prospectively (1003, 72.8% had No SLEDAI). Patients with SLEDAI had longer disease duration that patients who did not have a SLEDAI (mean: 6.3 vs. 5.2 years, p=0.007), were less likely to have been described as mild at diagnosis (no SLEDAI mild: 18.7%; SLEDAI mild: 11.3%, p=0.0004) and consulted more with health care professionals in the past 12 months (no SLEDAI mean visits: 6.5, SLEDAI mean: 7.7, p Patients with a BILAG index had flared more in the last 12 months (no BILAG: 30.6%, BILAG: 45.1%, p=0.0126). Physicians provided data on 220 SLEDAI and 75 BILAG assessments, extracted from the 2010 & 2013 DSPs. Multiple linear regression analyses revealed that flaring in the last 12 months (Coef: 3.27 [0.36 – 6.18], p=0.028), renal symptoms (Coef: 5.67 [1.84-9.51], p=0.004), and muscular symptoms (Coef: 4.58 [1.22-7.94], p=0.008) were all associated with a higher SLEDAI score, with r-squared 0.1948. Multiple linear regression showed that renal symptoms (Coef: 3.87 [1.00 – 6.75], p=0.009) were associated with a higher BILAG score, with r-squared 0.3717. Conclusion: The use of SLEDAI and BILAG index in clinical practice is limited and seemingly reserved for use in more severe patient cohorts; understanding the ongoing impact of this selective use on the treatment and management of SLE would be beneficial. Additionally, understanding the drivers and barriers to the use of disease activity metrics is important to improve the management of SLE in the future. Disclosure of Interests: Karen Costenbader: None declared, Ben Hoskin Employee of: Adelphi, Christian Atkinson Employee of: Adelphi, David Bell Employee of: Adelphi, Olivia Massey Employee of: Adelphi Real World, Jennifer H. Lofland Employee of: Janssen Global Commercial Strategic Organization, Pam Berry Shareholder of: GSK and Janssen Global Services, Chetan Karyekar Shareholder of: J&J, Employee of: Janssen Scientific Affairs, LLC, Abbott, BMS, Novartis, Zahi Touma Grant/research support from: GSK Canada, Consultant for: UBC, Pfizer, Janssen, Inc

Background Systemic lupus erythematosus (SLE) is autoimmune disorder often characterized by the development of glomerulonephritis. The use of mycophenolate mofetil (MMF) is highlighted as induction and maintenance therapy in lupus nephritis. We evaluated the treatment outcome of MMF in lupus nephritis patients from a real clinical practice. Methods Patients with biopsy proven lupus nephritis (class III, IV, and V) between November 2005 and August 2017 in Severance Hospital were extracted, and those patients who were treated with MMF at least 3 months were included in this study. The remission rate of lupus nephritis and risk factors for failure of remission were evaluated using Kaplan-Meier analysis and Cox proportional hazards model. Results Of 116 patients included in this study, 89 (76.7%) patients achieved remission of lupus nephritis after treatment with MMF. The median time to remission was 4.2 months (interquartile range 0.9 9.1). Normal complement level, negative result of anti-dsDNA antibody, and nephrotic range proteinuria were risk factors for remission failure in univariate analysis (p=0.017, 0.001, and 0.007, respectively). Nephrotic range proteinuria and negative result of anti-dsDNA antibody are independently associated with remission failure in multivariate analysis (OR 3.19, p=0.004 and OR 1.62, p=0.028, respectively). Conclusions Patients with lupus nephritis showed a favourable clinical outcome after MMF treatment. However, additional therapy would be required in patients with nephrotic-range proteinuria and without anti-dsDNA antibody. Funding Source(s): None

Systemic lupus erythematosus (SLE) is a heterogeneous disease, characterised by a wide spectrum of clinical manifestations (ranging from arthritis and skin manifestations to renal insufficiency or central nervous system involvement)...

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

BackgroundThe real-world effectiveness of intravenous (IV) belimumab in treating systemic lupus erythematosus (SLE) has been demonstrated in various countries through the OBSErve (evaluation Of use of Belimumab in clinical practice SEttings) program. Here we describe the clinical effectiveness of IV belimumab for treating SLE in real-world clinical practice in the Russian Federation.MethodsIn the retrospective, observational OBSErve Russia study (GSK Study 215349), eligible physicians enrolled adults with SLE receiving IV belimumab as part of their standard care. De-identified data were collected from patient medical records from September 2021 to March 2022. The primary outcome was the physician-assessed overall clinical response at 6 months post-index versus index (belimumab initiation) among patients receiving belimumab for ≥6 months. Other endpoints included change in Safety of Estrogens in Lupus Erythematosus National Assessment – SLE Disease Activity Index (SELENA-SLEDAI) score and glucocorticoid use.ResultsOverall, 59 patients initiated IV belimumab, mainly due to the previous regimen not being effective and to decrease glucocorticoid use (76.3% each); 15.3% of patients started belimumab within the first year of SLE diagnosis. Only 13.6% of patients discontinued belimumab within the first 6 months, mainly due to loss to follow-up and loss of insurance/reimbursement. At 6 months post-index, among patients who completed ≥6 months of belimumab therapy (full analysis set, n = 53), 90.6% and 60.4% had an overall clinical improvement of ≥20% and ≥50%, respectively. Mean (standard deviation, SD) change in SELENA-SLEDAI score from index to 6 months post-index was −5.9 (4.3). Mean (SD) glucocorticoid dose decreased from 12.2 (7.3) mg/day at index to 8.6 (5.1) mg/day at 6 months post-index (n = 50).ConclusionsPatients with SLE receiving IV belimumab for 6 months in real-world settings in the Russian Federation experienced overall clinical improvements and reductions in glucocorticoid use, which is an important long-term strategy of SLE treatment.

Successful treatment of severe chronic cutaneous lupus with anifrolumab: A series of 6 cases

The efficacy and safety of levilimab (LVL) in patients with active rheumatoid arthritis (RA) has been confirmed in controlled clinical trials. This article presents the results of a preliminary analysis of a non-interventional observational study of LVL in RA patients. Objective: to evaluate the efficacy and safety of LVL in the treatment of patients with RA in real-world clinical practice. Materials and methods. The HELIOS study is a retrospective-prospective, multicenter, non-interventional study of retention rate of LVL therapy and the safety of LVL in patients with RA in real-world clinical practice. Patients received medical care, including LVL, according to routine clinical practice for the treatment of RA and Russian instructions for medical use of the drug. This article presents the results of an analysis of the efficacy and safety of LVL after 12 and 24 weeks of treatment. Efficacy was assessed using the DAS28-CRP/ESR, SDAI, CDAI and patient assessment of pain, fatigue and morning stiffness according to VAS (0–100 mm). Results and discussion. 524 patients from 42 medical centers in the Russian Federation were enrolled in the study from June 2022 to November 2023. The majority of patients were female (83.2 %) and the mean age of patients was 53 years. A statistically significant decrease in DAS28-CRP/ESR, SDAI, CDAI, patient assessment of pain, fatigue and morning stiffness (VAS) was observed after 12 and 24 weeks of treatment, regardless of previous treatment with biologics or Jak inhibitors (JAKi). LVL was well tolerated by patients, the most frequently reported adverse events were infections, changes in peripheral blood and laboratory abnormalities characteristic of treatment with IL-6R inhibitors. Conclusion. In real-world clinical practice, LVL has been shown to be highly effective and well tolerated in patients with RA when prescribed as the first biologic disease-modifying antirheaumatic drus (bDMARD) and after switching from other bDMARDs or JAKi.

ObjectiveTo examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting.MethodsThis observational cohort study...

New-onset autoantibody-mediated nephritis during ustekinumab therapy for psoriasis in patients with and without prior systemic lupus erythematosus

Background:Anifrolumab is a biological treatment with recent approval for systemic lupus erythematosus (SLE), supported by its efficacy in clinical trials. However, data from real clinical practice are lacking.Objectives:To describe the...

The development of irreversible organ damage (IOD) in systemic lupus erythematosus (SLE) significantly increases the risk of death, worsens the quality of life and significantly increases the cost of treatment. The development and implementation of specific tools that will promote early identification of the risk of unfavorable outcomes is a priority. The article presents literature review on a new method for prediction of unfavorable outcomes in SLE – frailty index (FI, vulnerability index). FI, developed by a group of international experts on the basis of the database of the international cohort of SLE patients – SLICC (Systemic Lupus International Collaborating Clinics) – is easily reproducible in real clinical practice and can be used in patients with an early stage of SLE to predict the risk of death, the development of IOD. and hospitalization. The SLE Forecasting index of unfavorable outcomes (SLICC-FI) appears to be a promising clinical and research tool for identifying those who need more careful monitoring and an individual therapeutic strategy at an early stage of the disease.

The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real-life, multicenter, international SLE population. We conducted a cross-sectional observational study of patients with a clinical diagnosis of SLE followed at the participating rheumatology centers and registered in the Portuguese and Spanish national registries. The sensitivity of the 2 classification sets was compared using McNemar's test. The sensitivity of ACR 1997 and SLICC 2012 was further examined in 5 subgroups, defined according to disease duration. We included 2,055 SLE patients (female 91.4%, white 93.5%, mean ± SD age at disease onset 33.1 ± 14.4 years, mean ± SD age at SLE diagnosis 35.3 ± 14.7 years, and mean ± SD age at the time of the study 47.4 ± 14.6 years) from 17 centers. The sensitivity for SLE classification was higher with the SLICC 2012 than with the ACR 1997 (93.2% versus 85.6%; P < 0.0001). Of 296 patients not fulfilling the ACR 1997, 62.8% could be classified with the SLICC 2012. The subgroup of patients with ≤5 years since disease onset presented the largest difference in sensitivity between the SLICC 2012 and the ACR 1997 (89.3% versus 76.0%; P < 0.0001); this difference diminished with longer disease duration, and it was no longer significant for patients with >20 years of disease duration. The SLICC 2012 criteria were more sensitive than the ACR 1997 criteria in real-life clinical practice in SLE. The SLICC 2012 criteria may allow patients to be classified as having SLE earlier in the disease course.

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