Bariatric Surgery and the Incidence of Rheumatoid Arthritis

A Swedish Obese Subjects Study

Cristina Maglio; Yuan Zhang; Markku Peltonen; Johanna Andersson-Assarsson; Per-Arne Svensson; Christian Herder; Anna Rudin; Lena Carlsson

Disclosures

Rheumatology. 2020;59(2):303-309. 

In This Article

Methods

SOS Study Design

The SOS is a longitudinal non-randomized study including 4047 subjects with obesity recruited at 25 surgical departments and 480 primary health care centres in Sweden between 1 September 1987 and 31 January 2001, as previously described.[15] Briefly, after a recruitment campaign in the media and at surgical departments and primary health care centres, 5335 subjects were found eligible at the matching examination. Of these, 2010 individuals chose to undergo bariatric surgery and constituted the surgery group. A matched control group of 2037 subjects was created, based on data from the matching examination. Matching was not performed at an individual level, but by using the method of sequential treatment assignment on the basis of 18 matching variables, as previously reported (sex, age, weight, height, hip circumference, waist circumference, systolic blood pressure, triglycerides, total cholesterol, postmenopausal status, daily smoking, diabetes, four psychosocial variables associated with death risk and two personality traits related to treatment preferences).[16,20] Ethical reasons did not allow randomization since six of seven Swedish ethics review boards considered the relatively high death rate following bariatric surgery unacceptable for randomization when the study was approved in 1987.[15,19] The surgery patient and the conventionally treated matched patient started the study on the same day (i.e. the day of the surgery). As previously reported, the matching process unexpectedly created a surgery group having a slightly higher mean body weight, a younger age and more severe risk factors than the control group.[15]

Inclusion and exclusion criteria were identical for both groups and all the participants from the control group were, in principle, eligible for surgery. Inclusion criteria were age 37–60 years and BMI ≥34 for men and ≥38 for women. Exclusion criteria were previous surgery for gastric or duodenal ulcer, earlier bariatric surgery, gastric ulcer during the previous 6 months, ongoing or active malignancy during the past 5 years, myocardial infarction during the past 6 months, bulimic eating pattern, drug or alcohol abuse, psychiatric or cooperative problems contraindicating bariatric surgery or other rare conditions.[21]

Subjects from the surgery group underwent bariatric surgery at baseline (19% gastric banding, 68% vertical banded gastroplasty and 13% gastric bypass). The control group received conventional non-surgical obesity treatment at their centres of registration (ranging from intensive lifestyle modifications to no treatment of any kind) and no attempt was made to standardize the non-surgical treatment.[22] All the subjects gave their written or oral informed consent to participate in the study. Seven Swedish local ethics review boards approved the study protocol. The study is registered at ClinicalTrials.gov with identifier NCT01479452.

Clinical and Biochemical Assessments

Centralized laboratory examinations were performed at matching, at baseline and at the 2-, 10-, 15- and 20-year follow-ups at the Central Laboratory of Sahlgrenska University Hospital. ESR was measured at the participants' health care centres at the time of health examination visits. CRP levels at baseline were measured with an ultrasensitive immunoturbidimetric method (Sentinel, Milan, Italy) using the Architect c8200 analyser (Abbott Laboratories, Abbott Park, IL) in Helsinki, Finland between October 2010 and April 2011. A sufficient number of serum samples for the measurement of CRP were available for 3693 participants at baseline, when excluding subjects with prevalent RA at baseline.

Health examinations were performed at matching, at baseline and after 6 months and 1, 2, 3, 4, 6, 8, 10, 15 and 20 years. BMI was calculated as weight in kilograms divided by the square of the height in metres. Changes in BMI at the 2 year follow-up were calculated as [(value at follow-up – baseline value)/baseline value] × 100. The variable called 'obesity duration' was created based on patients' self-reported weight at different ages and age at baseline. The first reported BMI (calculated from self-reported weight) ≥30 after 20 years of age was considered as obesity debut. Obesity duration was defined as the time period from obesity debut to baseline age.

Outcome

The endpoint of this report was the diagnosis of RA, which is not a predefined endpoint of the SOS study. The primary endpoint of the SOS study was mortality. Secondary endpoints included type 2 diabetes and cardiovascular disease.[21] To identify SOS study participants with a diagnosis of RA, the Swedish National Patient Register was searched for the following International Classification of Diseases (ICD) codes for RA: 712.38 and 712.39 (ICD-8), 714.0–2 (ICD-9) and M05, M06.0, M06.8 and M06.9 (ICD-10). The National Patient Register includes medical records from both inpatient and outpatient visits all over Sweden. Inpatient care visits have been documented since 1964, but the register reached national coverage only in 1987. The outpatient register does not include data about primary care, only visits to hospital-based medical specialists, and became nationwide in 2001. Information about serostatus was obtained by a review of the ICD codes; subjects who were seronegative at the diagnosis of RA but later developed seropositivity according to the ICD codes were classified as seropositive.

Based on the National Patient Register, all study participants who had a diagnosis of RA before inclusion in the study were considered as having 'a prevalent RA' and were therefore excluded from the current study. The subjects who developed RA after baseline were considered as having incident RA. Participants were followed up until diagnosis of RA, death, migration or end of follow-up. The cut-off date for the current analyses was 31 December 2016. At the end of follow-up, 924 study participants died or were censored due to emigration. Information on death or migration was obtained from the Cause of Death Register and the Register of the Total Population.[23]

Statistical Analysis

Baseline characteristics of the study population are shown as mean (S.D.) or number (%). Baseline continuous variables were compared by general linear model test, whereas categorical variables were compared by χ2 tests.

Kaplan–Meier method estimates of cumulative incidence rates have been used to assess time to incident RA after inclusion. Comparisons between groups were performed by log-rank test. Hazard ratios (HRs) and corresponding 95% CIs for the risk of RA were calculated with Cox proportional hazard models.

The intention-to-treat principle was used in all analyses unless otherwise specified. In the per-protocol analysis, participants from the control group who underwent bariatric surgery during follow-up were censored at the time of surgery. Among those subjects, study participants who developed RA were censored only if the diagnosis was made after the day of the surgery. Two-sided P-values <0.05 were considered statistically significant. Statistical analyses were performed with the Statistical Package for Social Science (version 24.0; IBM, Armonk, NY, USA).

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