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BACKGROUND: Allopurinol is a frequently used, effective, and affordable medication for gout. However, poor adherence to allopurinol is a key reason for patients not reaching treatment goals. The aim of this study was to comprehensively assess factors associated with high allopurinol adherence in gout. METHODS: In this national cohort study, we used the health-care databases of the US Department of Veterans Affairs (VA) from 2002 to 2016 and a new-user design to assess potential predicting factors of allopurinol adherence. Veterans were included in this study if they had International Classification of Diseases (ninth revision) code 274.x for gout in two or more outpatient encounters or one or more inpatient encounters during 2002-16; incident allopurinol use; and at least 12 months of observation. Potential predictors of allopurinol adherence (defined as medication possession ratio [days used divided by days prescribed] of >80%) were examined using Andersen's health-care utilisation model and multivariable-adjusted logistic regression analyses. FINDINGS: Between Oct 1, 2002, and Sept 30, 2016, 565 812 potentially eligible patients were included in the VA database, of whom 264 614 (46·8%) met the eligibility criteria and were included in the study cohort. The mean age was 67·8 years (SD 11·7) and mean body-mass index was 33·0 kg/m2 (6·4). Factors significantly associated with higher odds of allopurinol adherence in multivariable-adjusted analyses were older age (odds ratio 1·01, 95% CI 1·01-1·01); Deyo-Charlson comorbidity index score of 1 (1·05, 1·02-1·07) or 2 or more (1·05, 1·03-1·07) versus a score of 0; higher body-mass index (all categories from 25 to <30 [1·12, 1·08-1·17] to ≥45 [1·47, 1·39-1·55] vs 18·5 to <25); a military service connection of 50% or higher (1·37, 1·29-1·46) versus 0%; care in a community-based outpatient clinic (1·11, 1·08-1·14) versus in a VA Medical Center; and rural residence (1·02, 1·00-1·05). Factors significantly associated with lower odds of allopurinol adherence were black (0·74, 0·72-0·76), Hispanic (0·68, 0·65-0·72), or other race or ethnicity (0·86, 0·82-0·89) versus white race; non-rheumatologist care provider (0·83, 0·79-0·88); allopurinol start dose of 101-200 mg per day (0·93, 0·91-0·95) or more than 300 mg per day (0·75, 0·72-0·79) versus 100 mg per day or less; or allopurinol use in the previous year (0·80, 0·79-0·82). Compared with residence in the Midwest, patients in other US regions had lower odds of adherence (mid-Atlantic 0·89, 0·87-0·92; northeast 0·84, 0·81-0·87; south 0·85, 0·83-0·88; west 0·86, 0·83-0·89). Compared with a baseline serum urate of 360 to less than 480 µmol/L, serum urate of less than 360 µmol/L was associated with higher odds of adherence (1·28, 1·25-1·32), whereas baseline serum urate of 480 to less than 600 µmol/L (0·86, 0·84-0·88) or 600 to less than 720 µmol/L (0·92, 0·89-0·94) was associated with lower odds of adherence. INTERPRETATION: We identified several important factors associated with high allopurinol adherence. Clinicians and policy makers can now target modifiable factors at the patient, provider, or systems level, with the aim of improving allopurinol adherence, and thereby overall gout care.
RESUMO
BACKGROUND: Prior studies have demonstrated abnormalities in the composition of the gastrointestinal microbiota in pediatric and adult patients with spondyloarthritis (SpA). In particular, diminished fecal abundance of Faecalibacterium prausnitzii and abnormalities in both directions in the abundance of the Bacteroides genus have been identified. METHODS: We obtained fecal specimens from 30 children with treatment-naïve enthesitis-related arthritis (ERA) and 19 healthy controls, as well as specimens from 11 adult patients with longstanding SpA and 10 adult healthy controls. All of the samples underwent sequencing of the 16S ribosomal DNA. A subset of the pediatric fecal samples was subjected to shotgun metagenomics sequencing. RESULTS: ERA patients had decreased abundance of the anti-inflammatory F. prausnitzii A2-165 strain (41 ± 28% versus 54 ± 20% of all sequences matching F. prausnitzii, p = 0.084) and an increased abundance of the control F. prausnitzii L2/6 strain (28 ± 28% versus 15 ± 15%, p = 0.038). Similar trends were observed in adults with longstanding SpA (n = 11) and controls (n = 10). In contrast, the fecal abundance of Bacteroides fragilis was increased in ERA subjects (2.0 ± 4.0% versus 0.45 ± 0.7% of all sequences, p = 0.045), yet was diminished in adult subjects (0.2 ± % versus 1.0 ± % of all sequences, p = 0.106). Shotgun metagenomics sequencing of the fecal DNA in the pediatric subjects revealed diminished coverage of the butanoate pathway (abundance normalized to controls of 1 ± 0.48 versus 0.72 ± 0.33 in ERA, p = 0.037). CONCLUSIONS: The anti-inflammatory F. prausnitzii A2-165 strain appears to be depleted in both pediatric and adult SpA. In contrast, B. fragilis may be depleted in adult disease yet abundant in pediatric SpA, suggesting developmental effects on the immune system.