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- Olsson, E. Kihlgren, et al.
(författare)
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BREAKTHROUGH SARS-COV-2 INFECTION IN FULLY VACCINATED PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM THE COVID-19 VACCINATION IN AUTOIMMUNE DISEASE (COVAD) STUDY
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 540-541
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Although many studies have been conducted on COVID-19 in recent years, there are still unanswered questions regarding breakthrough infections (BTIs), particularly in patients with systemic lupus erythematosus (SLE).Objectives: This study aimed to determine the occurrence of breakthrough COVID-19 infections in patients with SLE versus other autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs).Methods: The study was based on data from the COVAD questionnaire which amassed a total of 10,783 complete responses from patients with SLE, AIRD, or nrAIRD, and HCs. After exclusion of individuals who were unvaccinated, those who received one vaccine dose only, and those with uncertain responses regarding the vaccine doses, a total of 9,595 patients formed the study population of the present investigation. If a COVID-19 infection occurred after the initial two vaccine doses and at least one booster dose (at least three doses in total, herein termed full vaccination), it was considered a BTI. Data were analysed using multivariable regression models. Statistically significant results were denoted by p values <0.05.Results: A total of 7,016/9,595 (73.1%) individuals were fully vaccinated. Among those, 1,002 (14.2%) reported at least one BTI, and 166 (2.3%) reported at least two BTIs. Among SLE patients, 867/1,218 (71.2%) were fully vaccinated. Among fully vaccinated SLE patients, 137 (15.8%) reported at least one BTI while 28 (3.2%) reported at least two BTIs. BTI frequencies in fully vaccinated SLE patients were comparable to those of other AIRDs (OR: 1.0; 95% CI: 0.8–1.3; p=0.447) and nrAIDS (OR: 0.9; 95% CI: 0.6–1.3; p=0.856) but higher compared with HCs (OR: 1.2; 95% CI: 1.0–1.6; p=0.022).For SLE patients with three vaccine doses, 113/137 (82.5%) reported at least one BTI while the corresponding number for four vaccine doses was 24/137 (17.5%). Compared with HCs (OR: 10.6; 95% CI: 1.2–93.0; p=0.032) and other AIRDs (OR: 3.5; 95% CI: 1.08–11.5; p=0.036), SLE patients showed higher frequencies of hospitalisation.AID multimorbidity was associated with a 15-fold increased risk for a need of advanced treatment for COVID-19 (OR: 15.3; 95% CI: 2.6–88.2; p=0.002).Conclusion: COVID-19 BTIs occurred in nearly 1 every 6th fully vaccinated patient with SLE, and 20% more frequently in this patient population compared with fully vaccinated HCs. Moreover, BTIs in SLE patients were more severe compared with BTIs in HCs or patients with AIRDs other than SLE, resulting in a greater need for hospitalisation. AID multimorbidity contributed to a more severe COVID-19 BTI requiring advanced management. These insights call for greater attention to vaccination in the vulnerable group of SLE patients, with appropriate risk stratification towards optimised vaccination strategies.
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- Parodis, Ioannis, 1981-, et al.
(författare)
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Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus : a post-hoc analysis of pooled data from five randomised clinical trials
- 2024
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.METHODS: In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [NCT00410384], BLISS-52 [NCT00424476], BLISS-NEA [NCT01345253], BLISS-SC [NCT01484496], and EMBRACE [NCT01632241]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White). FINDINGS: Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28-45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants vs 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15-1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32-52 (week 52: 322 [17%] of 1869 participants vs 125 [10%] of 1217 participants; 1·74 [1·44-2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was significantly higher among patients in the belimuab group than those who received placebo from week 44 in all baseline subgroups denoting high disease activity or earlier in some subgroups, and the differences were maintained at week 52.INTERPRETATION: In adults with active SLE, belimumab plus standard therapy yielded greater benefit than placebo plus standard therapy in attaining DORIS remission (for which low rates were attained in both groups) and LLDAS, with differences observed as early as week 28 for DORIS remission and week 8 for LLDAS.FUNDING: Swedish Rheumatism Association, King Gustaf V's 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and the Karolinska Institutet.
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- Parodis, Ioannis, 1981-, et al.
(författare)
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Effect of Belimumab on Preventing de novo Renal Lupus Flares
- 2023
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Ingår i: Kidney international reports. - : Elsevier. - 2468-0249. ; 8:9, s. 1822-1830
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Belimumab was recently approved for treating lupus nephritis (LN), yet de novo LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative.METHODS: We evaluated belimumab efficacy in preventing de novo renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis.RESULTS: Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. Asian origin (Adjusted Hazard Ratio [HRadj]: 1.97; 95% confidence interval [CI]: 1.32-2.94; P = 0.001), positive baseline anti-double stranded DNA (anti-dsDNA) levels (HRadj: 1.32; 95% CI: 1.07-1.63; P = 0.008), and increasing mean prednisone dose during follow-up (HRadj: 1.03; 95% CI: 1.02-1.04; P < 0.001) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg monthly) yielded a nearly 3-fold lower hazard of de novo renal flare (HRadj: 0.38; 95% CI: 0.20-0.73; P = 0.004). Subcutaneous (SC) belimumab (200 mg weekly) also yielded a lower hazard (HRadj.: 0.69; 95% CI: 0.54-0.88; P = 0.003). The labeled IV dose (10 mg/kg monthly) conferred no clear protection (HRadj.: 0.74; 95% CI: 0.50-1.09; P = 0.127).CONCLUSION: We corroborated the substantial vulnerability of the Asian SLE population to renal affliction. Add-on low-dose IV belimumab (1 mg/kg) and SC belimumab appeared protective against renal flares in nephritis-naïve patients with SLE. The approved IV dose (10 mg/kg) yielded no clear protection.
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- R., Naveen, et al.
(författare)
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COVID-19 vaccination in autoimmune diseases (COVAD) Study : vaccine safety and tolerance in rheumatoid arthritis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:7, s. 2366-2376
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The COVID-19 vaccination in autoimmune diseases (COVAD) study aimed to assess short-term COVID-19 vaccination-related adverse events (AEs) in rheumatoid arthritis (RA) patients.METHODS: An online self-reported questionnaire (March-December 2021) was used to capture data related to COVID-19 vaccination-related AEs in RA, other autoimmune rheumatic diseases (AIRDs) (excluding RA and inflammatory myositis), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). Descriptive and multivariable regression analyses were performed.RESULTS: Of the 9462 complete respondents, 14.2% (n = 1347) had been diagnosed with RA who had a mean (standard deviation) age of 50.7 (13.7) years, and 74.2% were women, and 49.3% were Caucasian. In total, 76.9% and 4.2% of patients with RA reported minor and major AEs, respectively. Patients with active and inactive RA had similar AE and hospitalization frequencies. Overall, AEs were reported more frequently by BNT162b2 and mRNA-1273 recipients and less frequently by BBV152 recipients compared with the rest. Major AE and hospitalization frequencies were similar across recipients of different vaccines. Patients receiving methotrexate and hydroxychloroquine reported fewer minor AEs than those patients not on them. Compared with HCs and patients with other AIRDs, patients with RA reported similar total AEs, overall minor AEs, and hospitalizations. Compared with nrAIDs, patients with RA reported lower frequencies of overall AEs, minor AEs (both OR = 0.7; 95%CI = 0.5-0.9), and injection site pain (OR = 0.6; 95%CI = 0.5-0.8) with similar major AE and hospitalization frequencies.CONCLUSION: Despite the differences in AE frequency across different COVID-19 vaccines, all were well tolerated in patients with RA and were comparable to HCs providing reassurance to the safety of COVID-19 vaccination.
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