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OBJECTIVE: Patients with rheumatoid arthritis (RA) treated with Janus Kinase inhibitors (JAKi) are at increased risk of Herpes Zoster (HZ). The objective of this study was to investigate serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. METHODS: RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect enzyme-linked immunosorbent assay (ELISA). Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. RESULTS: Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (p< 0.0001). 80.5% of patients and 98.0% of controls achieved a ≥ 4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls (ratio 0.44, 95% CI 0.31-0.63), and lower in patients receiving JAKi+Methotrexate than JAKi monotherapy (ratio 0.43, 95% CI 0.24-0.79). AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. CONCLUSION: The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for usage of the HZ/su vaccine in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03886038.
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OBJECTIVES: The aim of this study of patients with RA in Sweden was to investigate secular trends in achieving sustained remission (SR), i.e. DAS28 <2.6 on at least two consecutive occasions and lasting for at least 6 months. METHODS: All adult RA patients registered in the Swedish Rheumatology Quality register through 2012, with at least three registered visits were eligible, a total of 29 084 patients. Year of symptom onset ranged from 1955, but for parts of the analysis only patients with symptom onset between 1994 and 2009 were studied. In total, 95% of patients fulfilled the ACR 1987 classification criteria for RA. Odds of reaching SR for each decade compared with the one before were calculated with logistic regression and individual years of symptom onset were compared with life table analysis. RESULTS: Of patients with symptom onset in the 1980s, 1990s and 2000s, 35.0, 43.0 and 45.6% reached SR, respectively (P < 0.001 for each increment), and the odds of SR were higher in every decade compared with the one before. The hazard ratio for reaching SR was 1.15 (95% CI 1.14, 1.15) for each year from 1994 to 2009 compared with the year before. Five years after symptom onset in 2009, 45.3% of patients had reached SR compared with 15.9% in 1999. CONCLUSION: There is a clear secular trend towards increased incidence of SR in patients with RA in Sweden. This trend most likely reflects earlier diagnosis and treatment start, and adherence to national and international guidelines recommending the treat to target approach.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Diagnóstico Precoce , Sistema de Registros , Indução de Remissão/métodos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Suécia/epidemiologia , Fatores de TempoRESUMO
Objectives: The aims of this national study in Sweden of patients with RA were to: examine the prevalence of sustained remission (SR), that is, remission lasting for at least 6 months; compare the prevalence of SR in patients with early RA and established RA; study the timing of onset of and time spent in SR; and study possible predictors of SR. Methods: Adult patients with RA included in the Swedish Rheumatology Quality registry were studied. The registry was searched for patients fulfilling remission criteria: DAS28-ESR, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and ACR/EULAR remission for at least 6 months. Early RA was defined as symptom duration ⩽6 months at inclusion in the Swedish Rheumatology Quality. Results: Of 29 084 patients, 12 193 (41.9%) reached DAS28 SR at some time point during follow-up compared with 6445 (22.2%), 6199 (21.3%) and 5087 (17.5%) for CDAI, SDAI and ACR/EULAR SR, respectively. SR was more common in early RA (P < 0.001). The median time from symptom onset to SR was 1.9, 2.4, 2.4 and 2.5 years according to DAS28, CDAI, SDAI and ACR/EULAR criteria, respectively. Lower age, male sex and milder disease characteristics were associated with SR. Conclusion: The majority of patients in this nationwide study never reached SR. Patients with early RA are more likely to reach SR than patients with established RA.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros , Indução de Remissão , Índice de Gravidade de Doença , Fatores Sexuais , Suécia/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To study the impact of disease and treatment with DMARDs on antibody response elicited by either pneumococcal conjugate vaccine (PCV13) or pneumococcal polysaccharide vaccine (PPV23) in patients with SSc. Methods: Forty-four SSc patients and 49 controls received a dose of either PCV13 or PPV23. Twelve patients were treated with DMARDs. Antibody levels to pneumococcal polysaccharides 6B and 23 F were measured before and 4-6 weeks after vaccination using ELISA. Antibody functionality was studied using opsonophagocytic assay performed on serotype 23 F. Results: Number of patients, percentage female and mean age (years) at vaccination were: 32, 94%, 57.5 years in SSc without DMARDs; 12, 100%, 55.5 years in SSc on DMARDs and 49, 63% and 50.6 years in controls. Post-vaccination antibody levels for both serotypes increased significantly in SSc without DMARDs and controls (P < 0.001), but in SSc on DMARDs only for 6B (P = 0.041). Compared with the other groups, patients with SSc receiving DMARDs had lower post-vaccination antibody levels for both serotypes. Opsonophagocytic assay increased significantly in all three groups. No significant difference in immunogenicity between PCV13 and PPV23 was seen. Conclusion: Pneumococcal vaccination using either PCV13 or PPV23 yielded satisfactory antibody response in SSc patients without DMARD treatment, but a lower response in patients treated with synthetic DMARDs. Type of pneumococcal vaccine (conjugate or polysaccharide) did not significantly influence antibody response. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02240888.
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Vacinas Pneumocócicas/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Streptococcus pneumoniae/imunologia , Vacinação/métodos , Anticorpos Anti-Idiotípicos/sangue , Anticorpos Anti-Idiotípicos/imunologia , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/imunologia , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/imunologia , Resultado do TratamentoRESUMO
OBJECTIVES: Tumour necrosis factor-α inhibitor (TNFi) treatment has been shown to reduce the rates of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). Our objective was to compare the effect of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) on AU occurrence in AS, using real-world data. METHODS: Patients with AS starting ADA, ETN or IFX as their first TNFi from January 2003 to December 2010 were extracted from the Swedish Rheumatology Quality Register. AU rates, based on visits to an ophthalmologist with International Classification of Diseases 10 codes for AU, were obtained by linkage to the Swedish National Patient Register. For each TNFi, AU rates 2â years before TNFi start and for the first 2â years on TNFi treatment were compared. In the subgroup of patients who were AU-free during the 2â years before TNFi start, we also compared the risk of a first AU event. RESULTS: 1365 patients with AS were included (406 ADA, 354 ETN, 605 IFX). Compared with pretreatment rates, we noted a reduction in overall AU rates for ADA and IFX, and an increase for ETN. The adjusted HRs for AU in 1127 patients who were free of AU in the last 2â years before TNFi start were significantly higher for ETN versus ADA (HR: 3.86 95% CI 1.85 to 8.06) and ETN versus IFX (HR: 1.99, 95% CI 1.23 to 3.22), while the HR for IFX versus ADA was not statistically significant. CONCLUSIONS: The results suggest differences in effect on AU risk between ADA, ETN and IFX, with a clear advantage for ADA/IFX over ETN.
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Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Etanercepte/uso terapêutico , Infliximab/uso terapêutico , Sistema de Registros , Espondilite Anquilosante/tratamento farmacológico , Uveíte Anterior/prevenção & controle , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Espondilite Anquilosante/complicações , Suécia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte Anterior/complicaçõesAssuntos
Hospedeiro Imunocomprometido , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Escleroderma Sistêmico/virologia , Vacinação , Adulto , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Masculino , Escleroderma Sistêmico/imunologiaRESUMO
OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs). METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins. RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001). CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.
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Antirreumáticos , COVID-19 , Doenças Reumáticas , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Abatacepte , Rituximab/uso terapêutico , Suécia , Antirreumáticos/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Interleucina-12 , Anticorpos AntiviraisRESUMO
Background: Dysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation. Methods: Citrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples. Results: C1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples. Conclusion: Citrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes impaired its ability to inhibit the complement and contact systems in vitro. Citrullination seems to render C1-INH more immunogenic, and citrullinated C1-INH might thus be an additional target of the autoantibody response observed in RA patients.
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Artrite Reumatoide , Citrulinação , Humanos , Desiminases de Arginina em Proteínas/genética , Fator XIIa/metabolismo , Calicreína Plasmática/metabolismo , Fator XIa , Proteínas/metabolismo , AutoanticorposRESUMO
Patients with rheumatoid arthritis (RA) have an increased risk of infections; therefore, immunization against vaccine-preventable diseases is important. Methotrexate (MTX) impairs the antibody response to pneumococcal conjugate vaccine (PCV) in patients with arthritis, and the underlying mechanism is largely unknown. Here, we investigate the potential role of the innate immune system in the faltering antibody response following PCV vaccination in RA patients treated with MTX. Phenotypes of circulating granulocytes and monocytes were analyzed in 11 RA patients treated with MTX, 13 RA patients without disease-modifying antirheumatic drug treatment (0DMARD), and 13 healthy controls (HC). Peripheral blood samples were collected before and 7 days after vaccination. In addition, the MTX group was sampled before initiating treatment. Frequencies of granulocyte and monocyte subsets were determined using flow cytometry. Serotype-specific IgG were quantified using a multiplex bead assay, pre- and 4-6 weeks after vaccination. At baseline, no differences in granulocyte and monocyte frequencies were observed between the groups. Within the MTX group, the frequency of basophils increased during treatment and was higher compared to the HC and 0DMARD groups at the prevaccination time point. MTX patients were categorized into responders and nonresponders according to the antibody response. Before initiation of MTX, there were no differences in granulocyte and monocyte frequencies between the two subgroups. However, following 6-12 weeks of MTX treatment, both the frequency and concentration of monocytes were lower in PCV nonresponders compared to responders, and the difference in monocyte frequency remained after vaccination. In conclusion, the suppressive effect of MTX on monocyte concentration and frequency could act as a biomarker to identify nonresponders to PCV vaccination.
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Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , Monócitos , Vacinas Pneumocócicas , Vacinas ConjugadasRESUMO
Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied. Blood samples were collected: before MTX, ≥ 4 weeks on stable MTX dose (prevaccination), and 7 days postvaccination (MTX group), and pre- and 7 days postvaccination (0DMARD and HC). Phenotypes of B- and T cell subsets were determined using flow cytometry. Serotype-specific IgG were quantified using multiplex bead assay, pre- and 4-6 weeks postvaccination. Concentrations of plasmablasts and switched memory B cells increased after PCV in HC (both p = 0.03) and the 0DMARD group (p = 0.01 and p = 0.02), but not in the MTX group. Postimmunization plasmablasts were lower in MTX group, compared to the 0DMARD group and HC (p = 0.002 and p < 0.001). Th17 cells decreased after MTX start (p = 0.02), and increased in HC after immunization (p = 0.01). Postimmunization plasmablasts correlated with mean antibody response ratio in all RA patients (R = 0.57, p = 0.035). Methotrexate reduced Th17 cells and blocked activation of plasmablasts and switched memory B cells following polysaccharide-protein conjugate antigen challenge in RA.
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Formação de Anticorpos/imunologia , Artrite Reumatoide/imunologia , Linfócitos B/imunologia , Metotrexato/uso terapêutico , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/imunologia , Streptococcus pneumoniae/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/microbiologia , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/prevenção & controle , VacinaçãoRESUMO
OBJECTIVE: To investigate the association between vaccinations in adults and the risk of developing rheumatoid arthritis (RA). METHODS: Data from the Swedish population-based Epidemiological Investigation of RA case-control study encompassing 1998 incident cases of RA aged 18-70 years and 2252 randomly selected controls matched for age, sex and residency were analysed. Those vaccinated within 5 years before disease onset were compared with those not vaccinated by calculating OR with 95% CI. RESULTS: Vaccinations neither increased the risk of RA overall (OR 1.0, 95% CI 0.9 to 1.1) nor the risk of two major subgroups of RA (antibodies to citrullinated peptide-positive (ACPA-positive) and ACPA-negative disease). Furthermore, vaccinations did not increase the risk of RA in smokers or carriers of HLA-DRB1 shared epitope alleles, two groups with established risk factors for RA. CONCLUSIONS: In this case-control study of incident cases of newly diagnosed RA, no increased risk of RA following immunisation was observed for vaccinations overall or for any specific vaccination. This indicates that immunological provocation of adults with commonly used vaccines in their present form carries no risk of RA. These findings should be implemented among public healthcare providers in order to encourage vaccinations according to recommended national vaccination schedules.
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Artrite Reumatoide/etiologia , Vacinação/efeitos adversos , Adolescente , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Estudos de Casos e Controles , Genótipo , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Pessoa de Meia-Idade , Peptídeos Cíclicos/imunologia , Fumar/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: Gout is predicted by a number of comorbidities and lifestyle factors. We aimed to identify discrete phenotype clusters of these factors in a Swedish population-based health survey. In these clusters, we calculated and compared the incidence and relative risk of gout. METHODS: Cluster analyses were performed to group variables with close proximity and to obtain homogenous clusters of individuals (n = 22,057) in the Malmö Preventive Project (MPP) cohort. Variables clustered included obesity, kidney dysfunction, diabetes mellitus (DM), hypertension, cardiovascular disease (CVD), dyslipidemia, pulmonary dysfunction (PD), smoking, and the use of diuretics. Incidence rates and hazard ratios (HRs) for gout, adjusted for age and sex, were computed for each cluster. RESULTS: Five clusters (C1-C5) were identified. Cluster C1 (n = 16,063) was characterized by few comorbidities. All participants in C2 (n = 750) had kidney dysfunction (100%), and none had CVD. In C3 (n = 528), 100% had CVD and most participants were smokers (74%). C4 (n = 3673) had the greatest fractions of obesity (34%) and dyslipidemia (74%). In C5 (n = 1043), proportions with DM (51%), hypertension (54%), and diuretics (52%) were highest. C1 was by far the most common in the population (73%), followed by C4 (17%). These two pathways included 86% of incident gout cases. The four smaller clusters (C2-C5) had higher incidence rates and a 2- to 3-fold increased risk for incident gout. CONCLUSIONS: Five distinct clusters based on gout-related comorbidities and lifestyle factors were identified. Most incident gout cases occurred in the cluster of few comorbidities, and the four comorbidity pathways had overall a modest influence on the incidence of gout.
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Gota , Comorbidade , Seguimentos , Gota/epidemiologia , Humanos , Incidência , Estilo de Vida , Fatores de Risco , Suécia/epidemiologiaRESUMO
OBJECTIVE: To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. METHODS: Patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4-8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 µg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 µg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F. RESULTS: Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient - 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients - 1.9 and - 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls. CONCLUSIONS: Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered.
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Antirreumáticos/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas Pneumocócicas/administração & dosagem , Doenças Reumáticas/tratamento farmacológico , Abatacepte/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunização Secundária/métodos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Doenças Reumáticas/imunologia , Rituximab/uso terapêuticoRESUMO
OBJECTIVE: To estimate the prevalence and incidence of non-gout crystal arthropathy in relation to socioeconomic factors in southern Sweden. METHODS: All patients (age ≥ 18 years) with at least one visit to a physician with the diagnosis of interest in the Skåne region (population of 1.3 million) in 1998-2014 were identified. Non-gout crystal arthropathy (ICD-10 codes M11.0-M11.9) was subclassified in four different groups: calcium pyrophosphate crystal deposition related arthropathy (CPPD), unspecified non-gout arthropathies, chondrocalcinosis, and hydroxyapatite crystal deposition disease. The crude and age-adjusted point prevalence on December 31, 2014, and the cumulative incidence during 2014 were calculated for all non-gout crystal arthropathies, CPPD, and other unspecified non-gout arthropathies overall and in relation to occupation, income, and level of education. RESULTS: The crude 2014 point prevalence (95% CI) and 2014 cumulative incidence (95% CI) of all non-gout crystal arthropathies were 0.23% (0.23-0.24) and 21.5 (19-25) cases/100,000 persons. Mean age (range) among all prevalent cases in 2014 was 71 (20-102) years and 56% were males. The point prevalence and cumulative incidence of CPPD were 0.09% (0.08-0.09) and 8 (7-10)/100,000 persons, respectively. The corresponding data for unspecified non-gout crystal deposition disease was 0.16% (0.16-0.17) and 15.6 (13-18)/100,000 persons, respectively. The prevalence and incidence of CPPD and unspecified non-gout crystal arthropathies were slightly higher in men and increased with age irrespective of gender. Unspecified non-gout crystal arthropathy but not CPPD was less prevalent in persons with ≥ 15 years of education, whereas there were no clear associations with occupation and income. CONCLUSION: The prevalence of all diagnosed non-gout crystal arthropathies was 0.23%, thus considerably less prevalent than gout in southern Sweden. CPPD and other unspecified non-gout crystal arthropathies are the predominant diagnoses, increasing with age and in men. With the exception for unspecified non-gout crystal arthropathies being inversely correlated to a higher level of education, no convincing association with the socioeconomic factors was found.
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Artropatias por Cristais/diagnóstico , Gota/diagnóstico , Sistema de Registros/estatística & dados numéricos , Fatores Socioeconômicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pirofosfato de Cálcio/química , Condrocalcinose/diagnóstico , Condrocalcinose/epidemiologia , Artropatias por Cristais/classificação , Artropatias por Cristais/epidemiologia , Durapatita/química , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Suécia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To examine cause-specific mortality beyond cardiovascular diseases (CVDs) in patients with gout compared to the general population. METHODS: We included all residents of Skåne (Sweden) age ≥18 years in the year 2002. Using the Skåne Healthcare Register, we identified subjects with a new diagnosis of gout (2003-2013) and matched each person with gout with 10 comparators free of gout, by age and sex. We used information on the underlying cause of death from the Swedish Cause of Death Register (through December 31, 2014) to estimate hazard ratios (HRs, with 95% confidence intervals [95% CIs]) of mortality for specific causes of death in a multi-state Cox model, with adjustment for potential confounders. RESULTS: Among 832,258 persons, 19,497 had a new diagnosis of gout (32% women) and were matched with 194,947 comparators. Subjects with gout had higher prevalence of chronic kidney disease, metabolic disease, and CVD. Gout was associated with 17% increased hazard of all-cause mortality overall (HR 1.17 [95% CI 1.14-1.21]), 23% in women (HR 1.23 [95% CI 1.17-1.30]), and 15% in men (HR 1.15 [95% CI 1.10-1.19]). In terms of cause-specific mortality, the strongest associations were seen in the relationship of gout to the risk of death due to renal disease (HR 1.78 [95% CI 1.34-2.35]), diseases of the digestive system (HR 1.56 [95% 1.34-1.83]), CVD (HR 1.27 [95% CI 1.22-1.33]), infections (HR 1.20 [95% CI 1.06-1.35]), and dementia (HR 0.83 [95% CI 0.72-0.97]). CONCLUSION: Several non-CV causes of mortality are increased in persons with gout, emphasizing the need for improved management of comorbidities.
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Doenças Cardiovasculares/mortalidade , Demência/mortalidade , Diabetes Mellitus/mortalidade , Doenças do Sistema Digestório/mortalidade , Gota/epidemiologia , Infecções/mortalidade , Insuficiência Renal Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Causas de Morte , Demência/epidemiologia , Diabetes Mellitus/epidemiologia , Doenças do Sistema Digestório/epidemiologia , Feminino , Humanos , Infecções/epidemiologia , Pneumopatias/epidemiologia , Pneumopatias/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Suécia/epidemiologiaRESUMO
Aim: To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. Methods: An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018). Results: While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved. Conclusion: Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.
Assuntos
Doenças Autoimunes/complicações , Controle de Doenças Transmissíveis , Doenças Transmissíveis/etiologia , Imunogenicidade da Vacina , Doenças Reumáticas/complicações , Vacinas/imunologia , Adulto , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/prevenção & controle , Resultado do Tratamento , Vacinação , Vacinas/administração & dosagem , Vacinas/efeitos adversosRESUMO
BACKGROUND: Pneumococcal vaccination is recommended to patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). However, little is known whether the diseases influence pneumococcal vaccine response. This study aimed to investigate antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in RA patients or pSS patients without disease modifying anti-rheumatic drugs (DMARD), compared to patients with RA treated with DMARD or to healthy controls. METHODS: Sixty RA patients (50 without DMARD and 10 with MTX), 15 patients with pSS and 49 controls received one dose of PCV13. Serotype-specific antibody concentrations for pneumococcal polysaccharides 6B and 23F and functionality of antibodies (23F) were determined in serum taken before and 4-6 weeks after vaccination using ELISA and opsonophagocytic activity assay (OPA), respectively. Proportions of individuals with positive antibody response (i.e. ≥ 2-fold increase from prevaccination concentrations; antibody response ratio; ARR ≥ 2), percentage of individuals reaching putative protective antibody level (i.e. ≥1.3 µg/mL) for both serotypes, and difference in OPA were calculated. RESULTS: After vaccination, antibody concentrations for both serotypes increased in RA without DMARD (p < 0.001), pSS (p ≤ 0.05 and < 0.01) and controls (p < 0.001). Antibody responses to 6B and 23F were comparable in RA without DMARD (64% and 74%), pSS (67% and 53%) and controls (65% and 67%), but lower in the small group RA with MTX (both 20%, p < 0.01). Similarly, significant increases of patients reaching protective antibody levels were seen in RA without DMARD (p ≤ 0.001) and controls (p < 0.001). After vaccination, OPA increased significantly in controls, RA and pSS without DMARD (p < 0.001 to 0.03), but not in RA with MTX. CONCLUSIONS: Pneumococcal conjugate vaccine is immunogenic in RA and pSS patients without DMARD and in line with previous studies we support the recommendation that vaccination of RA patients should be performed before the initiation of MTX. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02240888. Retrospectively registered 4 September, 2014.