Does a family history of RA influence the clinical presentation and treatment response in RA?

Frisell, Thomas; Saevarsdóttir, Saedís; Askling, Johan

doi:10.1136/annrheumdis-2015-207670

Cited by 14 publications

(9 citation statements)

References 27 publications

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“…Similarly, Alazmi et al (36) found no association between family history of SpA and 6 month BASDAI50 response in axial SpA patients in Canada. In RA, a related but less familial disease, family history was not associated with TNFi treatment outcome among Swedish patients (44). These findings are in line with ours, showing a lack of association of family history with both drug survival and treatment response.…”

Section: Discussionsupporting

confidence: 89%

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study

Morin

Hellgren

Lindström

et al. 2021

Scandinavian Journal of Rheumatology

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Objective: To determine whether a family history of spondyloarthritis (SpA) is associated with clinical presentation at the start of tumour necrosis factor inhibitor (TNFi) treatment, or predictive of TNFi drug survival and treatment response in patients with SpA. Method: Family history of SpA in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated SpA (uSpA) from the Swedish Rheumatology Quality register starting a TNFi as their first biologic in 2006-2018 was assessed through national registers. Clinical characteristics at treatment start were compared by family history status. We used Cox regression to estimate hazard ratios for drug discontinuation, and analysed treatment response at 3 and 12 months with linear regression. Multiple imputation was used to address missing data. Results: We included 9608 patients. Patients with family history had an earlier age at onset and longer disease duration at TNFi treatment start, but did not differ regarding disease activity and presence of SpA manifestations. Hazard ratios for drug discontinuation were 1.08 [95% confidence interval (CI) 0.89-1.31] for AS patients with a family history of AS, 1.02 (95% CI 0.89-1.18) for PsA patients with a family history of PsA, and 1.11 (95% CI 0.85-1.45) for uSpA patients with a family history of uSpA, after adjusting for demographic, socioeconomic, and SpA-related factors. Treatment response at 3 and 12 months was similar between groups. Conclusion: Family history of SpA was not found to be associated with clinical presentation at the start of TNFi treatment, nor was it associated with drug survival or treatment response in SpA patients starting a first TNFi.

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Section: Discussionsupporting

confidence: 89%

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study

Morin

Hellgren

Lindström

et al. 2021

Scandinavian Journal of Rheumatology

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“…The present study extends our previous findings in which we investigated familial aggregation of EULAR response to treatment with MTX in monotherapy and tumor necrosis factor inhibitors (TNFi) [ 11 ]. Due to small sample sizes, that study could not investigate familial aggregation within MTX-treated individuals, but found a significant familial component related to TNFi discontinuation after 12 months.…”

Section: Discussionsupporting

confidence: 83%

“…Few studies have studied treatment persistence as the outcome, which, in a treat-to-target paradigm should serve as a proxy for favorable tolerance and sustained treatment response. Using persistence as the outcome measure, a previous study from our group found that family history of RA, in itself , was unable to predict persistence to MTX in DMARD monotherapy at 3 and 6 months, though that study did not take family history of MTX treatment response into account [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?

et al. 2022

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Objectives To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability. Methods First-degree relative pairs diagnosed with RA 1999–2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient. Results Familial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87–1.20), only at 3 (RR=1.41, 95% CI 1.14–1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0–0.43) and 0.58 (95% CI 0.27–0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis. Conclusions Our findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.

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“…In the present study, we focused on FDR‐RA who are considered at high risk to develop RA themselves. In fact, the family history of RA is one of the strongest risk factors for RA and a strong independent predictor for RA onset: in first‐degree relatives, the increased risk is from twofold to fourfold (Frisell, Saevarsdottir, & Askling, ). The Study Group for Risk Factors for Rheumatoid Arthritis was recently established by the European League Against Rheumatism (EULAR) Committee in order to develop specific recommendations for terminology to be used when describing different phases of the disease when conducting clinical studies (Gerlag et al., ).…”

Section: Discussionmentioning

confidence: 99%

Periodontal status correlates with anti‐citrullinated protein antibodies in first‐degree relatives of individuals with rheumatoid arthritis

Loutan

Alpizar-Rodriguez

Courvoisier

et al. 2019

J Clinic Periodontology

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Aim To evaluate periodontal status in first‐degree relatives of patients with rheumatoid arthritis (FDR‐RA) and detect correlation with the presence of anti‐citrullinated protein antibodies (ACPAs). Materials and Methods Rheumatologic status and periodontal status were evaluated in a nested case–control study of FDR‐RA with no diagnosis of RA at enrolment. The following parameters were assessed in 34 ACPA‐positive (ACPA+) and 65 ACPA‐negative (ACPA−) subjects: gingival index (GI), plaque index (PI), probing depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). We compared the two groups using conditional logistic regression. Results In ACPA+ individuals, the mean, PD, BOP, CAL and number of sites per person with PD > 4 mm and BOP were significantly higher compared to the ACPA‐ group. All ACPA+ subjects had periodontitis: 44.1% presenting moderate and 47.1% severe periodontitis. ACPA‐ subjects had mainly mild (30.8%) and moderate (27%) periodontitis, differences being significantly different for both moderate periodontitis (p = 0.001) and severe periodontitis (p < 0.001). In multivariable analyses, ACPA status (p = 0.04) and age (p = 0.002) were significantly and independently associated with periodontal conditions. Conclusion High prevalence and severity of periodontitis in FDR‐RA was associated with seropositivity to ACPAs. This further strengthens the hypothesis that periodontitis may be a risk factor in the development of RA.

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Does a family history of RA influence the clinical presentation and treatment response in RA?

Abstract: Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial.

Cited by 14 publications

References 27 publications

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study

Is family history a predictor of response to tumour necrosis factor inhibitors in spondyloarthritis? A Swedish nationwide cohort study

Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?

Periodontal status correlates with anti‐citrullinated protein antibodies in first‐degree relatives of individuals with rheumatoid arthritis

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