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- Nordmark, G., et al.
(författare)
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Association of Genes in the NF-kappa B Pathway with Antibody-Positive Primary Sjogren's Syndrome
- 2013
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 78:5, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Primary Sjogren's syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens. Experimental studies have shown an activation of NF-B in primary SS. NF-B activation results in inflammation and autoimmunity and is regulated by inhibitory and activating proteins. Genetic studies have shown an association between multiple autoimmune diseases and TNFAIP3 (A20) and TNIP1 (ABIN1), both repressors of NF-B and of IKBKE (IKK epsilon), which is an NF-B activator. The aim of this study was to analyse single nucleotide polymorphisms (SNPs) in the IKBKE, NFKB1, TNIP1 and TNFAIP3 genes for association with primary SS. A total of 12 SNPs were genotyped in 1105 patients from Scandinavia (Sweden and Norway, n=684) and the UK (n=421) and 4460 controls (Scandinavia, n=1662, UK, n=2798). When patients were stratified for the presence of anti-SSA and/or anti-SSB antibodies (n=868), case-control meta-analysis found an association between antibody-positive primary SS and two SNPs in TNIP1 (P=3.4x10(-5), OR=1.33, 95%CI: 1.16-1.52 for rs3792783 and P=1.3x10(-3), OR=1.21, 95%CI: 1.08-1.36 for rs7708392). A TNIP1 risk haplotype was associated with antibody-positive primary SS (P=5.7x10(-3), OR=1.47, 95%CI: 1.12-1.92). There were no significant associations with IKBKE, NFKB1 or TNFAIP3 in the meta-analysis of the Scandinavian and UK cohorts. We conclude that polymorphisms in TNIP1 are associated with antibody-positive primary SS.
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- Crisci, E., et al.
(författare)
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Complement Opsonization Promotes Herpes Simplex Virus 2 Infection of Human Dendritic Cells
- 2016
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 90:10, s. 4939-4950
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus 2 (HSV-2) is one of the most common sexually transmitted infections globally, with a very high prevalence in many countries. During HSV-2 infection, viral particles become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of immune responses. In genital mucosa, the primary target cells for HSV-2 infection are epithelial cells, but resident immune cells, such as dendritic cells (DCs), are also infected. DCs are the activators of the ensuing immune responses directed against HSV-2, and the aim of this study was to examine the effects opsonization of HSV-2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV-2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV-2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV-1- or HSV-2-specific antibodies more or less abolished HSV-2 infection of DCs. Our results clearly demonstrate the importance of studying HSV-2 infection under conditions that ensue in vivo, i.e., conditions under which the virions are covered in complement fragments and complement fragments and antibodies, as these shape the infection and the subsequent immune response and need to be further elucidated. During HSV-2 infection, viral particles should become coated with complement proteins and antibodies, both present in genital fluids, which could influence the activation of the immune responses. The dendritic cells are activators of the immune responses directed against HSV-2, and the aim of this study was to examine the effects of complement alone or complement and antibodies on HSV-2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses. Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV-2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV-2 pathogenesis.
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- Di Giuseppe, D, et al.
(författare)
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DIFFERENCES IN DRUG SURVIVAL BETWEEN ORIGINATOR AND BIOSIMILAR PRODUCTS AMONG FIRST USERS OF EACH MOLECULE
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 535-535
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Biosimilar products of biological disease-modifying antirheumatic drugs (bDMARDs) entered the Swedish market in 2015, with regulatory approvals based on head to head trials of limited duration. Longer-term comparative drug survival, in clinical practice, remains less well documented.Objectives:To compare survival on drug between biosimilars and their originator products among first starters of etanercept, infliximab, adalimumab and rituximab.Methods:Data from the Swedish Rheumatology Quality register (SRQ) was used to identify and follow patients who started a first ever treatment with etanercept since April 2015 (originator=ETA,biosimilar= SB4), infliximab since March 2014 (originator=IFX,biosimilar= CT-P13), adalimumab since January 2018 (originator=ADA biosimilars=SB5, ABP501), or rituximab since January 2018 (originator=RIT,biosimilar= GP2013), through December 31st, 2019, date of first discontinuation of the drug, or death. Discontinuation was defined as lack of effectiveness or adverse events, while other reasons for interruption of the drug (including non-medical switch) were considered censoring events. Descriptive characteristics were collected from the SRQ and tabulated. Hazard ratios (HR) of discontinuation were estimated using Cox regression, with each drug analyzed separately, adjusted for age,sex,indication,line of treatment,disease duration,year of treatment start,region and concomitant use of csDMARD.Results:9274 patients started etanercept(49% SB4), 3609 started infliximab(64% CT-P13), 3117 started adalimumab(27% SB5, 14% ABP 501), and 763 started rituximab(39% GP2013), Table 1. Patients starting CT-P13 and GP2013 were less likely to be biologics-naïve compared to those starting the originator product. Initiators of SB5,ABP501 and GP2013 were more likely,and those starting CT-P13 were less likely,to be on concomitant csDMARDs compared to those starting the originator products. Patients characteristics of ETA and SB4 were similar.The introduction of a biosimilar was typically followed by a decrease in the uptake of the originator, but for ETA a change in pricing in 2018 later led to a reversal of this pattern (Figure 1).For IFX,ADA,and RIT, survival on drug was similar for the originator and its biosimilar(s). For ETA,risk of discontinuation was somewhat lower for the biosimilar than for the originator(adjusted HR:0.87,95% confidence interval:0.79-0.95), Table 1.Table 1.Hazard ratios of discontinuation and descriptive characteristics of biosimilar vs. originator among first starters of each molecule, until 31st December 2019.EtanerceptInfliximabAdalimumabRituximabOriginatorSB4OriginatorCT-P13OriginatorSB5ABP 501OriginatorGP2013N47214553130823011834852431465298Discontinuation12891236582878399139805726Adjusted hazard ratios*Ref0.87 (0.79-0.95)Ref1.14 (0.99-1.31)Ref1.02 (0.83-1.26)1.16 (0.88-1.52)Ref1.12 (0.68-1.85)Age, mean years (std)51 (16)51 (15)49 (16)49 (16)48 (15)52 (15)51 (15)59 (15)60 (15)Female, %67%65%61%64%62%64%65%75%76%RA, %46%48%39%35%33%42%43%61%76%Bionaïve, %72%72%76%69%45%52%43%53%38%Disease duration, mean years (std)11 (12)11 (11)11 (11)11 (11)12 (13)12 (11)14 (15)14 (19)15 (11)DAS28, mean4.0 (1.3)4.0 (1.4)4.1 (1.4)4.1 (1.4)3.7 (1.4)3.8 (1.3)4.0 (1.3)4.5 (1.4)4.7 (1.4)Concomitant csDMARDs, %45%47%57%48%37%49%42%36%43%Abbreviations: RA=rheumatoid arthritis. csDMARDs=conventional synthetic DMARD, std=standard deviation.Figure 1.Number of starts of biosimilars compared to the originator during the follow-up time, by moleculeConclusion:Despite their identical indications and therapeutic positioning, there are some differences in the baseline characteristics between patients who start ADA, IFX and RIT and their biosimilars. There are no differences in drug survival between originator and biosimilar with the possible exception of etanercept although the observed difference should be interpreted in light of possible unmeasured or residual channeling.Disclosure of Interests:Daniela Di Giuseppe: None declared, Hannah Bower: None declared, Bénédicte Delcoigne: None declared, Thomas Frisell: None declared, Katerina Chatzidionysiou Consultant of: Eli Lilly, AbbVie and Pfizer, Ulf Lindström: None declared, Christopher Sjowall: None declared, Elisabet Lindqvist: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB,
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- Gomez, A., et al.
(författare)
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LOW-DOSE BELIMUMAB AND ANTIMALARIAL AGENTS PREVENT RENAL FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM FOUR RANDOMISED CLINICAL TRIALS
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1467-1468
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Lupus nephritis (LN) is one of the most severe manifestations in systemic lupus erythematosus (SLE), constituting a substantial cause of end-stage kidney disease, dialysis, and mortality. Prompt and adequate treatment of LN, and prevention of renal flares are key components of disease management towards improved outcomes in patients with SLE.Objectives: We aimed to determine the effect of the use of antimalarial agents (AMA) and different doses and pharmaceutical forms of belimumab on preventing renal flares in patients with active SLE.Methods: We pooled data from the BLISS-52, BLISS-76, BLISS-SC and BLISS-Northeast Asia randomised clinical trials of belimumab (N=3225), that included patients with seropositive (antinuclear antibody titres ≥1:80 and/or anti-dsDNA levels ≥30 IU/mL), active SLE yet no severe ongoing renal disease. Participants were allocated to receive intravenous (IV) belimumab 1 mg/kg (N=559), IV belimumab 10 mg/kg (N=1033), subcutaneous (SC) belimumab 200 mg (N=556) or placebo (N=1077) in addition to standard therapy. Additionally, we classified patients as AMA users if they had received hydroxychloroquine, chloroquine, mepacrine, or quinine sulphate in stable doses for at least 30 days prior to the trial commencement. The outcome of the present post-hoc analysis was development of renal flares, defined according to the analysis plan within the BLISS programme. The hazard of renal flare was assessed with Cox proportional hazards regression models, adjusted for age, sex, ethnicity, previous renal involvement, baseline proteinuria and glomerular filtration rate, and use of glucocorticoids and immunosuppressants.Results: In total, 192 patients developed a renal flare after a median of 197 days. In multivariable Cox regression analysis, use of AMA was associated with a lower risk of renal flares (HR: 0.64; 95% CI: 0.54–0.96; p=0.026). Compared with placebo, the risk of renal flares was lower among patients receiving IV belimumab 1 mg/kg (HR: 0.44; 95% CI: 0.25–0.79; p=0.006) and IV belimumab 10 mg/kg (HR: 0.63; 95% CI: 0.45–0.87; p=0.005), but not SC belimumab 200 mg (HR: 0.90; 95% CI: 0.57–1.42; p=0.648). When analysing all study arms with and without antimalarials separately, patients receiving IV belimumab 1 mg/kg along with AMA experienced the lowest rate of renal flares (18.5 (7.4–38.1) cases per 1000 person-years). Using patients who received placebo but not AMA as the reference comparator, patients receiving IV belimumab 1 mg/kg (OR: 0.30; 95% CI: 0.13–0.70; p=0.005) and patients receiving IV belimumab 10 mg (OR: 0.45; 95% CI: 0.27–0.75; p=0.002) were protected against renal flares only when belimumab use was combined with AMA.Conclusion: In this RCT setting, belimumab and AMA protected against renal flares in patients with active seropositive SLE yet no ongoing severe renal involvement. The protective effect of IV belimumab against renal flares appeared optimal when belimumab was combined with AMA. The prominent effect of low-dose belimumab motivates investigation of the efficacy of intermediate doses of belimumab.
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- Lonnblom, E, et al.
(författare)
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AUTOANTIBODIES TO JOINT PROTEINS AS NOVEL BIOMARKERS FOR THE DIAGNOSIS OF UNTREATED EARLY RHEUMATOID ARTHRITIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 546-546
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies to citrullinated protein (ACPA; measured as anti-CCP; aCCP) and rheumatoid factor (RF) appear years before clinical onset of RA and are essential tools in today’s classification criteria for RA. In animal models, antibodies to joint specific proteins (JP) can induce arthritis, and they are also present at onset of RA [1]. As there is a need for increased precision for early diagnosis of RA as well as identification of different subtypes of the disease, we aim to assess whether autoantibodies to native or modified JP can be used for early and precise diagnosis of RA.ObjectivesTo study whether antibodies to JP, alone or in combination with ACPA/RF, could increase the diagnostic sensitivity and specificity in untreated early (ue)RA patients.MethodsAntibodies to JP were analysed in serum from patients in three independent ueRA cohorts as well as from population controls without rheumatic diseases (WINGA, Gothenburg and MFM-ÅUS, Malmö n=1062). ERAp (n=66), the smallest and most recent cohort was chosen for screening, and BARFOT and TIRA-2 (n=1939) for validation. We have developed a bead-based multianalyte flow immunoassay [2] and screened approx. 350 peptides derived from JPs of interest. We included monoclonal antibodies as assay calibrators and determined limit of detection (LoD). To assess positivity for autoantibodies to JP of interest above LoD, we used 5MAD (median absolute deviation) of the control populations as the cut-off.ResultsIn the ERAp cohort, 5 autoantibodies discriminated RA patients from controls with 81% sensitivity and 100% specificity (Table 1). The same autoantibodies had 68% sensitivity and 98% specificity in the combined BARFOT and TIRA-2 cohorts. Together with RF and aCCP, only 2 of the 5 autoantibodies added statistically significant diagnostic value, increasing the sensitivity from 48% to 61% with 99% specificity. In aCCP- and RF-negative ueRA patients (n=536), the novel biomarkers identified 22.5% of the patients with 99% specificity compared to controls.Table 1.Diagnostic capacity of the joint-specific antibodiesTest panelPerformanceGroup of patientsaCCP+RF+JP+SensitivitySpecificityAUC(ROC)ERApAll patients (n=66)--X81%100%89%RF and aCCP-neg patients (n=7)1------BARFOT and TIRA-2, combined dataAll patients (N=1939)--X68%98%86%All patients (N=1939)X--58%99%78%All patients (N=1939)2XX-48%100%84%All patients (N=1939)2, 3XXX61%99%86%RF and/or aCCP-pos patients (N=1403)--X84%99%93%RF and aCCP-neg patients (N=536)--X22%99%67%RA, literature valuesAnti-CCP testXN/AN/A53–71%95–96%N/A1Not analysed due to lack of power2This patient population is both aCCP+ and RF+3Only 2 of the 5 autoantibodies added statistically significant to the diagnostic valueAUC, Area under the curve; ROC, receiver operating characteristic curve; N/A, not applicable. Controls without rheumatic diseases: N=935 for BARFOT / TIRA-2 and N=27 for ERAp.ConclusionAutoantibodies to JP discriminate ueRA patients better then aCCP and RF alone and add an increased diagnostic value in particular for seronegative patients.References[1]Holmdahl, R., V. Malmstrom, and H. Burkhardt, Autoimmune priming, tissue attack and chronic inflammation - the three stages of rheumatoid arthritis. Eur J Immunol, 2014. 44(6): p. 1593-9.[2]Viljanen, J., et al., Synthesis of an Array of Triple-Helical Peptides from Type II Collagen for Multiplex Analysis of Autoantibodies in Rheumatoid Arthritis. ACS Chem Biol, 2020. 15(9): p. 2605-2615. Correction: ACS Chem Biol, 2020. 15(11): p. 3072AcknowledgementsBARFOT study group.Disclosure of InterestsErik Lönnblom: None declared, Monica Leu Agelii: None declared, Outi Sareila Employee of: Part time employee in Vacara AB, Ingiäld Hafström: None declared, Maria Andersson: None declared, Lei Cheng: None declared, Göran Bergström: None declared, Anna-Karin H Ekwall: None declared, Anna Rudin: None declared, Alf Kastbom: None declared, Christopher Sjowall: None declared, Bingze Xu: None declared, Lennart T.H. Jacobsson: None declared, Johan Viljanen: None declared, Jan Kihlberg: None declared, Inger Gjertsson: None declared, Rikard Holmdahl Shareholder of: Rikard Holmdahl the founder of Vacara AB.
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- Parodis, Ioannis, 1981-, et al.
(författare)
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PREDICTORS OF DE NOVO RENAL FLARES IN SYSTEMIC LUPUS ERYTHEMATOSUS - TIME TO REVISIT BELIMUMAB DOSE FOR EXTRA-RENAL DISEASE? : RESULTS FROM FIVE PHASE III CLINICAL TRIALS OF BELIMUMAB
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 909-910
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Each lupus nephritis (LN) flare causes nephron loss that equals a decade or more of reduction in renal function lifespan, making prompt initiation of therapy imperative and prevention of flares even more desirable. Identification of readily available signals of imminent flare is therefore expected to improve prognosis.Objectives: In light of observed cases of de novo LN during belimumab treatment (1), we evaluated predictors of de novo renal flare occurrence in patients with systemic lupus erythematosus (SLE) and no prior history of renal disease undergoing standard therapy (ST) with or without add-on belimumab in clinical trial settings.Methods: Data from five clinical trials of belimumab in SLE (BLISS-52 NCT00424476; BLISS-76 NCT00410384; BLISS-NEA NCT01345253; BLISS-SC NCT01484496; EMBRACE NCT01632241) were utilised. The study population comprised 1932 patients with a baseline renal British Isles Lupus Assessment Group (BILAG) score E. De novo renal flares were defined as a change from renal BILAG E to A or B within a 52-week follow-up. Comparisons of baseline data were made using the Mann-Whitney U test, Pearson’s chi-squared (χ2) test or Fisher’s exact test as appropriate. Predictors of renal flare occurrence were investigated using univariable and multivariable Cox regression analysis. p values <0.05 were considered statistically significant.Results: De novo renal flares were documented in 146 (7.6%) patients. Among patients who developed at least one renal flare, greater proportions were Asians (30.8% versus 20.2%; p<0.003), had positive baseline anti-dsDNA levels (74.0% versus 61.3%; p=0.003), and had low baseline levels of C3 (51.4% versus 38.2%; p=0.002) and C4 (45.2% versus 35.8%; p=0.030) compared with patients who did not flare. In univariable Cox regression analysis, azathioprine use was protective against renal flares (HR: 0.70; 95% CI: 0.49–0.99; p=0.047), while anti-Sm positivity at baseline showed a trend towards an association with imminent renal flare (HR: 1.68; 95% CI: 0.99–2.85; p=0.057). In multivariable Cox regression analysis adjusting for age, sex, ethnicity, serum creatinine, and variables that differed significantly in univariable analysis, Asian ancestry (HR: 1.60; 95% CI: 1.03–2.49; p=0.036), high mean prednisone dose from baseline until renal flare occurrence or throughout the follow-up (HR: 1.03; 95% CI: 1.02–1.05; p<0.001), and baseline serum creatinine (HR: 1.02; 95% CI: 1.01–1.03; p=0.001) were associated with imminent de novo renal flare, while extra-renal clinical SLE Disease Activity Index 2000 (cSLEDAI) showed a negative association (HR: 0.92; 95% CI: 0.86–0.98; p=0.007). Notably, use of belimumab 1 mg/kg by intravenous (IV) infusion yielded a nearly 3 times decreased hazard of renal flare (HR: 0.37; 95% CI: 0.20–0.68; p=0.001), whereas IV belimumab 10 mg/kg and belimumab 200 mg administered subcutaneously (SC) displayed no clear protection.Conclusion: Asian patients appeared particularly susceptible to new-onset renal involvement, corroborating the substantial vulnerability of Asian SLE populations to renal affliction. Add-on low-dose IV belimumab on top of ST appeared protective against renal flares in SLE patients with no prior history of nephritis, while addition of the approved 10 mg/kg IV belimumab dose and SC belimumab yielded no clear protection. Discrepant results between low and high/approved belimumab doses warrant in-depth mechanistic exploration of underlying reasons e.g., potential effects of belimumab on B cell subsets that acquire regulatory properties.Reference: [1]Parodis I, Vital EM, et al. Rheumatology (Oxford). 2021;60(9):4348-54.
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- Walhelm, T., et al.
(författare)
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FACTORS ASSOCIATED WITH SURVIVAL AND DISCONTINUATION OF ANTIMALARIAL AGENTS IN SYSTEMIC LUPUS ERYTHEMATOSUS : RESULTS FROM A SWEDISH LONGITUDINAL REGISTRY
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 902-903
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hydroxychloroquine (HCQ) and chloroquine, referred to as antimalarial agents (AMA), are cornerstone drugs in systemic lupus erythematosus (SLE), which inhibit type I interferon release via toll-like receptor binding and increasing the pH in plasmacytoid dendritic cell lysosomes [1]. AMA use has established benefits in SLE, such as improved prognosis and decelerated accrual of organ damage. Use of HCQ is safe for most patients and serious side-effects are uncommon, even during pregnancy. Medical therapy to prevent repeated disease flares is of essential weight in the treatment of SLE. However, it is well-known that non-adherence to prescription of AMA is a considerable problem [2].Objectives: The aim of this cross-sectional study was to investigate the frequency of AMA prescription, and evaluate factors associated with ongoing use and discontinuation of AMA in a Swedish SLE population.Methods: We retrieved data from the Clinical Lupus Register in North-Eastern Gothia (Swedish acronym: KLURING), a longitudinal research and quality registry, including all prevalent and incident cases of SLE in the Östergötland County from 2008 onwards. All included subjects fulfilled the validated 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and had been diagnosed from 1963 onwards. Factors associated with ongoing use and discontinuation of AMA were investigated using logistic regression analysis, Mann-Whitney U test and chi-square test.Results: A total of 328 subjects were included in the analysis. The mean age at diagnosis was 40.0 years (range: 3–85; standard deviation [SD]: 17.7) and 85.7% were females. The mean SLICC/ACR damage index (SDI) score at last visit was 2.0 (range: 0—11; SD: 2.5). In total, 92.4% had used AMA at some point during their disease course (“ever” users; Table 1). Data from the last available visit indicated that 73.2% were currently prescribed AMA, exclusively HCQ, yielding a daily mean HCQ dose of 228.0 mg (range: 100—400; SD: 71.0). Among individuals who had discontinued AMA, 25.9% had developed a contraindication, mostly on ophthalmological basis (33.3%). Less common reasons were cardiac conditions (19.0%) and renal failure (9.5%). Subjective side-effects were also common; the most frequently reported were gastrointestinal symptoms (n=20/37). Most common patient-related factor associated with discontinuation was intentional non-adherence (e.g., low motivation; 8/11). Patients who had discontinued AMA showed a higher SDI score at the last visit (mean: 2.9; SD: 2.8; mean follow-up: 20.0 years) compared with patients on AMA (mean: 1.4; SD: 1.8; p=0.001; mean follow-up: 15.3 years). Those who fulfilled the immunological disorder ACR criterion (ACR-10) were more likely to continue on AMA (p=0.003). No significant differences were found regarding gender or smoking status. Conclusion: The vast majority of patients in KLURING had been exposed to AMA, and approximately 25% discontinued AMA therapy during follow-up. The main reason for discontinuation were therapy-related factors, such as contraindications and experience of side-effects. Above 50% of the reported side-effects that led to discontinuation were gastrointestinal symptoms. The group of discontinued AMA users accrued more damage over time.References:[1]Crow MK, Rönnblom L. Type I interferons in host defence and inflammatory diseases. Lupus Sci Med 2019;6:e000336[2]Costedoat-Chalumeau N, Houssiau F, Izmirly P, et al. A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires. Clin Pharmacol Ther 2018;103:1074-1082
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