Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?
Abstract 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 m...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02873-z |
| _version_ | 1798038053850185728 |
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| author | Anton Öberg Sysojev Thomas Frisell Bénédicte Delcoigne Saedis Saevarsdottir Johan Askling Helga Westerlind |
| author_facet | Anton Öberg Sysojev Thomas Frisell Bénédicte Delcoigne Saedis Saevarsdottir Johan Askling Helga Westerlind |
| author_sort | Anton Öberg Sysojev |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T21:34:58Z |
| format | Article |
| id | doaj.art-7732adb597394987b52fb1bef19b3551 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-11T21:34:58Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-7732adb597394987b52fb1bef19b35512022-12-22T04:01:47ZengBMCArthritis Research & Therapy1478-63622022-08-012411910.1186/s13075-022-02873-zDoes persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?Anton Öberg Sysojev0Thomas Frisell1Bénédicte Delcoigne2Saedis Saevarsdottir3Johan Askling4Helga Westerlind5Clinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteClinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteClinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteClinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteClinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteClinical Epidemiology Division, Department of Medicine Solna, Karolinska InstituteAbstract 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.https://doi.org/10.1186/s13075-022-02873-zRheumatoid arthritisMethotrexateHeritabilityFamilialityTreatment persistence |
| spellingShingle | Anton Öberg Sysojev Thomas Frisell Bénédicte Delcoigne Saedis Saevarsdottir Johan Askling Helga Westerlind Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? Arthritis Research & Therapy Rheumatoid arthritis Methotrexate Heritability Familiality Treatment persistence |
| title | Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? |
| title_full | Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? |
| title_fullStr | Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? |
| title_full_unstemmed | Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? |
| title_short | Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component? |
| title_sort | does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component |
| topic | Rheumatoid arthritis Methotrexate Heritability Familiality Treatment persistence |
| url | https://doi.org/10.1186/s13075-022-02873-z |
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