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- Frodlund, M., et al.
(författare)
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Predictors Of Antibody Response To Covid-19 Vaccine In Rituximab Treated Patients With Inflammatory Rheumatic Diseases. A Swedish Nationwide Study (Covid19-Reuma)
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 368-369
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In line with other reports, our group showed that patients treated with rituximab had significant impaired antibody response compared to patients treated with other biologic and targeted and synthetic disease modifying anti-rheumatic drugs (csDMARD).ObjectivesTo investigate predictors of response to COVID-19 vaccination (2 doses of mRNA vaccines, 2 doses of virus vector vaccines or combinations of these) in patients with inflammatory rheumatic diseases (IRD) treated with rituximab and controls.MethodsAntibody levels to three antigens: Spike protein full length, Spike S1 and Nucleocapsid C-terminal fragment (to confirm previous COVID-19 infection) were measured in sera collected before vaccination and 2-12 weeks after the second vaccine using a multiplex bead-based serology assay. The antigen-specific cut-off was defined as the median fluorescence intensity signal plus 6x standard deviations across 12 pre-pandemic controls. A good vaccine response was defined as having antibodies over the cut-off level for both spike antigens. Proportion (%) responders was compared between patients and controls (Chi2 test).Patients with IRD receiving last rituximab treatment within a mean (range) 193 (23-501) days before first vaccination participated. Individuals without IRD served as a control group. Predictors of a good vaccine response were explored using multivariate logistic regression analysis adjusted for age, sex, disease duration, diagnosis (systemic vasculitis/RA/JIA/other), concomitant csDMARD, rituximab dose and prednisolone dose. Hazard ratio (chanse) of a good antibody response in relation to time between the last rituximab treatment and vaccination was studied by Kaplan-Meier survival analysis.ResultsIn total, 145 patients receiving rituximab and 61 controls were inclyded. Of these, 82 received rituximab as monotherapy (67% women; mean age 66 years, mean disease duration 13 years; 33% had RA/JIA and 60% vasculitis) and 63 received rituximab+csDMARD (62% women; mean age 66 years; mean disease duration 17 years; 76% had RA/JIA and 10 % vasculitis). Controls (n=61) were 74% women and mean age 49 years. Compared to controls, rituximab patients had lower antibody levels for both spike proteins (p<0.001). Proportion (%) responders among patients receiving rituximab as monotherapy (40.2%) and rituximab+DMARDs (25.4%) was significantly lower than in controls (98.4%) (p<0.001, Chi2). Higher age, concomitant csDMARD at vaccination and shorter time from last rituximab treatment predicted impaired antibody response (multivariate logistic regression model) (Table 1). Longer time between the last rituximab course and vaccination was associated with better antibody response (Figure 1).Table 1.Predictors of good antibody response to two doses of COVID-19 vaccine defined as antibodies over the cut-off level for both spike antigensBp-valueOR95% CIAge at vaccination (years)-0.040.0090.960.93-0.99Sex (male/female)-9.550.2090.580.24-1.36csDMARD at vaccination (yes/no)-1.080.0260.340.13-0.88Prednisolone (mg/dag)-0.100.1030.900.80-1.02Rituximab dos (1000 mg vs 500 mg)-0.010.3700.990.99-1.00Time between the last rituximab and vaccination (months)0.200.0011.311.11-1.55Diagnosis at vaccination (systemic vasculitis vs others)-0.510.3150.600.21-1.64Figure 1.The chance of good antibody response following two doses of COVID-19 vaccine in relation to time between the last rituximab course and vaccination.ConclusionPatients with IRD getting vaccinated with two doses of COVID19 vaccine during the treatment with rituximab have the ability to develop antibody response although the response is impaired. For each month passed after the last rituximab course, the chance of good antibody response increases with 30%. Younger patients receiving rituximab as monotherapy and vaccinated preferably several months after the last rituximab treatment have the highest chance of achieving a good antibody response.AcknowledgementsUnrestricted research grants have been received from Roche and starting grants from The Swedish Rheumatism AssociationDisclosure of InterestsMartina Frodlund: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Anna Södergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Sophie Olsson: None declared, Anders Bengtsson: None declared, Lars Klareskog Grant/research support from: has eceived research grants from Pfizer, BMS, Affibody, Sonoma Biotherapeutics, Meliha C Kapetanovic Consultant of: have received consultancy fees from Abbvie, Pfizer and GSK, Grant/research support from: have received unrestricted research grants from Roche and Pfizer
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- Frodlund, M., et al.
(författare)
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The impact of immunomodulating treatment on the serological immunogenicity following three doses of covid-19 vaccine and persistence of immunogenicity of two vaccine doses in patients with inflammatory rheumatic diseases - a swedish study (covid19-reuma)
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 533-533
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Data on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.Objectives To elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.Methods Antibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.Results In total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118; 68% female; mean age 67 years), abatacept (n=18; 72% female; mean age 64 years), IL6r inhibitors (n=60; 73% female; mean age 64 years), JAK-inhibitors (n=44; 80% female, mean age 52 years), TNF-inhibitors (n=59; 70% female; mean age 47 years;), IL12/23/17 inhibitors (n=24; 46% female; mean age 54 years) and controls (n=36; 75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.Conclusion In this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.
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- Lourido, L., et al.
(författare)
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Circulating centromere protein F autoantibodies for predicting clinical response to infliximab in rheumatoid arthritis
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1399-1399
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- One third of patients with rheumatoid arthritis (RA) respond poorly to TNF inhibitors and related studies are inconsistent in predictive biomarkers. The identification of biomarkers that predict the treatment response prior to drug exposure is a current priority on the RA field. ACPA and RF are ubiquitously tested in RA patients, but other autoantibodies exist and may provide additional information on RA treatment response.Objectives:This study aimed to identify circulating autoantibodies for predicting response to infliximab (IFX) in RA.Methods:We profiled the autoantibody repertoire of baseline sera from 155 biologic naïve RA patients treated with IFX. The sera were provided by three independent clinical sources and distributed in one exploratory cohort (N=20) collected from Hospital Clínico Universitario of Santiago de Compostela (Spain), one replication cohort (N=61) collected from Hospital Universitario de A Coruña (Spain) and samples from the Swedish Farmacotherapy (SWEFOT) trial (Sweden) (N=74) for clinical validation. The presence of autoantibodies and their levels in serum were analysed in association with EULAR clinical response at 6 months follow-up: good response (GR, N=56), moderate (MR, N=55) and non-response (NR, N=44). A suspension bead array platform built on protein fragments within Human Protein Atlas and selected from an initial untargeted screening using an array containing 42000 antigens was employed to identify the IgG and IgA autoantibodies on the exploratory cohort. A replication and validation phases were carried out on the other two serum sample cohorts. Meta-analysis and Receiver Operating Curves were performed in order to assess the clinical relevance of the findings observed.Results:Meta-analysis revealed that the levels in serum of IgG autoantibodies against Centromere protein F (CENPF) are significantly increased in responders (good responders and moderate responders; N=111) to IFX compared to non-responders (N=44) (P=0.018). CENP-F is a proliferation-associated and cell cycle-dependent centromere autoantigen that might be involved in the increased or abnormal cell proliferation that occurs during RA process. The combination of the anti-CENPF antibodies with clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate the patients that will respond to IFX, showing an AUC of 0.756 (95% CI [0.639-0.874], P=0.001).Conclusion:High serum levels of IgG anti-CENPF antibodies might be potentially useful to identify RA patients more likely to benefit from IFXDisclosure of Interests:Lucía Lourido: None declared, Cristina Ruiz-Romero: None declared, flor picchi: None declared, Naomi Diz-Rosales: None declared, Sergio Vilaboa-Galán: None declared, Carlos Fernández-López: None declared, Jose Antonio Pinto Tasende: None declared, Eva Perez-Pampin: None declared, Cristina Regueiro Expósito: None declared, ANTONIO MERA VARELA: None declared, Antonio Gonzalez: None declared, Karen Hambardzumyan: None declared, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Peter Nilsson: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer
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