Background: Rheumatoid arthritis (RA) is categorized as seropositive or seronegative referring to the presence or absence of IgM rheumatoid factor (IgM-RF) and/ or anti-citrullinated protein antibodies (ACPA).
Patients with an autoimmune disease are more likely to develop additional autoimmune conditions than individuals without pre-existing autoimmune disease.
Objectives: The aims of this study were to examine patterns of polyautoimmunity in seropositive compared with seronegative patients with recent-onset RA.
Methods: The study was register-based and used the nationwide DANBIO register (identification of recent-onset (<1 year) seropositive, ICD-10 M05, and seronegative, M06, RA patients) linked to the Danish National Patient Registry and the Danish National Prescription Registry to obtain information on additional autoimmune diseases (see
Characteristics, prevalence, and incidence of polyautoimmunity in incident RA patients.
Seropositive | Seronegative | |
N | 7983 | 4534 |
Age in years | 59.4 (48.6 to 69.1) | 63.0 (51.5 to 72.3) |
Women | 5476 (69 %) | 2856 (63 %) |
HAQ-DI | 0.857 (0.375 to 1.375) | 0.875 (0.375 to 1.375) |
DAS28-CRP | 4.3 (3.3 to 5.2) | 4.6 (3.6 to 5.5) |
CRP, mg/mL | 10 (4 to 23) | 10 (3 to 26) |
VAS physician, 0-100mm | 27 (15 to 45) | 30 (16 to 47) |
Treated with methotrexate | 86 % | 84 % |
-other csDMARD, % | 24 % | 24 % |
-Biological DMARD, % | 5 % | 6 % |
Smoking status:
| 13 / 11 / 17 / 59 % | 9 / 9 / 23 / 59 % |
Prevalence of polyautoimmunity /
| 549 (10.6 %) /
| 349 (12.8 %) /
|
Age and sex adjusted odds ratio | 0.79 (0.71 to 0.89) | 1 (ref.) |
Incident cases of polyautoimmunity | 373 (4.7 %) | 242 (5.3 %) |
Adjusted hazard ratio | 0.86 (0.71 to 1.05) | 1 (ref.) |
Continuous variables shown as median with interquartile ranges. Autoimmune conditions included:
autoimmune thyroid disease (redeemed prescriptions of ATC=H03A); diabetes mellitus type 1 (ICD-10 diagnosis E10 combined with redeemed prescriptions of insulin, ATC=A10A); pernicious anaemia (D51.0); autoimmune haemolytic anaemia (D59.1); idiopathic thrombocytopenic purpura (D69.3); Autoimmune adrenalitis (E27.1B); multiple sclerosis (G35); neuromyelitis optica (G36.0); Guillain-Barré syndrome (G61.0); myasthenia gravis (G70); inflammatory bowel disease (K50-1); primary biliary cirrhosis (K74.3); primary sclerosing cholangitis (K83.0); autoimmune hepatitis (K75.4); celiac disease (K90.0); pemphigus vulgaris (L10.0); bullous pemphigoid (L12.0); dermatitis herpetiformis (L13.0); alopecia areata (L63); vitiligo (L80); lichen sclerosis (L90.0); chronic interstitial cystitis (N30.1).
Using age and sex adjusted logistic regression analysis, the odds ratio (OR) of prevalent polyautoimmunity in seropositive compared with seronegative patients at the time of RA diagnosis was calculated.
To estimate the hazard ratio (HR) for developing yet another autoimmune disease in the 5 years after RA diagnosis, adjusted cause-specific Cox regression models were performed. Several sensitivity analyses were carried out including alternative exposure and outcome definitions.
Results: In total, 12,517 patients with recent-onset RA were included. The groups were similar in terms of disease characteristics and DMARD treatment, but seropositive patients were younger and included more women, see
Conclusion: Patients with seropositive RA had a slightly lower prevalence and incidence of polyautoimmunity compared to seropositive patients. The results were somewhat surprising, yet very robust, and thus raises the question if seronegative RA is in fact “more autoimmune” despite the absence of (identified) autoantibodies.
Acknowledgements: We acknowledge all patients and all Danish departments of rheumatology contributing to the DANBIO registry.
Disclosure of Interests: Amalie Hagelskjær: None declared, René Cordtz: None declared, Sofie Bliddal: None declared, Anders Sandermann Mortensen: None declared, Salome Kristensen: None declared, Claus Henrik Nielsen: None declared, Ulla Feldt-Rasmussen: None declared, Christian Torp-Pedersen: None declared, Lene Dreyer Grant/research support from: Grants from BMS, Galderma, and Eli Lilly