Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive.

BACKGROUND: The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. METHODS: Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. RESULTS: In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). CONCLUSION: In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Effectiveness of Tofacitinib in Patients Initiating Therapy for Psoriatic Arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

INTRODUCTION: Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently. OUTCOMES: mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates. RESULTS: Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months. CONCLUSIONS: This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05195814.

Disparities in burden of disease in patients with rheumatoid arthritis across racial and ethnic groups.

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

Real-World Evidence Assessing Psoriatic Arthritis by Disease Domain: An Evaluation of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Real-world studies assessing treatment response by psoriatic arthritis (PsA) domains are limited. This study aimed to describe the patient characteristics, frequency and combinations of disease domains, disease activity, and patient-reported outcomes (PROs) by PsA domains in patients who initiated treatment with a tumor necrosis factor inhibitor (TNFi) or interleukin-17 inhibitor (IL-17i). METHODS: Adults with PsA who initiated treatment with a TNFi or an IL-17i between January 2013 and January 2021 and had a 6 (±3)-month follow-up were included. The prevalence of PsA domains, the most common domain combinations, treatment persistence, and unadjusted change in disease activity and PROs from baseline to 6 months for each PsA domain were summarized descriptively. RESULTS: Of the 1005 eligible patients, 63% were receiving TNFi and 37% were receiving IL-17i. Forty percent of TNFi and 14% of IL-17i initiators received these treatments as first-line therapy. Peripheral arthritis and skin disease were the most common PsA domains identified in 86% and 82% of patients, respectively, and the triad of peripheral arthritis, skin disease, and nail psoriasis was the most common domain combination observed in 14% of patients. More than two thirds (68%) of patients remained on therapy at 6 months' follow-up. Improvements in disease activity and PROs were observed across all PsA domains in those receiving TNFi or IL-17i. CONCLUSION: This real-world analysis highlights the heterogeneity in domain presentation; therefore, assessing all PsA domains is important for optimal disease management. Improvements in outcomes across all PsA domains demonstrate the effectiveness of TNFi and IL-17i in diverse patient groups exhibiting different phenotypes of PsA.

Examining the potential direct cardiovascular benefit of tumor-necrosis factor inhibitor in rheumatoid arthritis: Natural and controlled direct effect analyses.

BACKGROUND/PURPOSE: Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI). METHODS: We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale. RESULTS: We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]. CONCLUSIONS: We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice.

Time-Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovascular Risk.

OBJECTIVE: It is unknown how the relationship between disease activity in rheumatoid arthritis (RA) and cardiovascular (CV) events may change over time. We examined the potentially time-varying association of RA disease activity to CV events. METHODS: We used the CorEvitas prevalent RA registry. The Clinical Disease Activity Index (CDAI) score category, averaged within each 6-month window since enrollment, was the exposure, and the outcome was major adverse CV events (MACEs). We used marginal structural models to estimate the hazard ratio (HR), comparing each CDAI score category with remission, allowing for differential association over time. We predicted MACE-free survival under several CDAI score scenarios. RESULTS: We found 44,816 eligible patients (77% female; mean age 58 years) with a crude event rate of 5.3/1000 person-years (median follow-up 3.4 years). The strongest association between higher CDAI score and MACEs was observed during the first 6 months of enrollment (HR for CDAI score low 2.29 [95% CI: 1.21-4.36], moderate 2.81 [95% CI: 1.46-5.43], and high 2.99 [95% CI: 1.48-6.02]). These estimates gradually diminished; by year 5, the HRs were 1.00 (95% CI: 0.49-2.05) for low, 1.18 (95% CI: 0.51-2.71) for moderate, and 1.04 (95% CI: 0.45-2.40) for high CDAI score. Predicted MACE-free survival suggested a potential decrease in MACEs with a hypothetical earlier transition to remission. CONCLUSION: The association of higher disease activity with CV events may be stronger earlier in the disease course of RA. Interventional studies may be warranted to precisely determine the effect of disease activity suppression on CV events in RA.

Wound Botulism Among Persons Who Inject Black Tar Heroin in New Mexico, 2016.

Outbreaks of wound botulism are rare, but clinicians and health departments should maintain suspicion for signs, symptoms, and risk factors of wound botulism among persons who inject drugs in order to initiate treatment quickly. This report describes an outbreak of three wound botulism cases among persons in two adjacent counties who injected drugs. Provisional information about these cases was previously published in the CDC National Botulism Surveillance Summary. All three cases in this outbreak were laboratory-confirmed, including one case with detection of botulinum toxin type A in a wound culture sample taken 43 days after last possible heroin exposure. Findings highlight the delay in diagnosis which led to prolonged hospitalization and the persistence of botulinum toxin in one patient.

Francisella tularensis infection in dogs: 88 cases (2014-2016).

OBJECTIVE: To characterize the epidemiology, clinical signs, and treatment of dogs with Francisella tularensis infection in New Mexico. ANIMALS: 87 dogs in which 88 cases of tularemia (1 dog had 2 distinct cases) were confirmed by the New Mexico Department of Health Scientific Laboratory Division from 2014 through 2016 and for which medical records were available. PROCEDURES: Dogs were confirmed to have tularemia if they had a 4-fold or greater increase in anti-F tularensis antibody titer between acute and convalescent serum samples or F tularensis had been isolated from a clinical or necropsy specimen. Epidemiological, clinical, and treatment information were collected from the dogs' medical records and summarized. RESULTS: All 88 cases of tularemia were confirmed by paired serologic titers; the first (acute) serologic test result was negative for 84 (95%) cases. The most common reported exposure to F tularensis was wild rodent or rabbit contact (53/88 [60%]). Dogs had a median number of 3 clinical signs at initial evaluation; lethargy (81/88 [92%]), pyrexia (80/88 [91%]), anorexia (67/88 [76%]), and lymphadenopathy (18/88 [20%]) were most common. For 32 (36%) cases, the dog was hospitalized; all hospitalized dogs survived. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with F tularensis infection often had nonspecific clinical signs and developed moderate to severe illness, sometimes requiring hospitalization. Veterinarians examining dogs from tularemia-enzootic areas should be aware of the epidemiology and clinical signs of tularemia, inquire about potential exposures, and discuss prevention methods with owners, including reducing exposure to reservoir hosts and promptly seeking care for ill animals.

Changes in Sugar-Sweetened Soda Consumption, Weight, and Waist Circumference: 2-Year Cohort of Mexican Women.

OBJECTIVES: To evaluate 2-year changes in soda consumption, weight, and waist circumference. METHODS: We followed 11 218 women from the Mexican Teachers' Cohort from 2006 to 2008. Dietary data were collected using a semiquantitative food frequency questionnaire. Weight was self-reported, and waist circumference was self-measured. We used linear regression to evaluate changes in sugar-sweetened and sugar-free soda consumption in relation to changes in weight and waist circumference, adjusting for lifestyle and other dietary factors. RESULTS: Compared with no change, a decrease in sugar-sweetened soda consumption by more than 1 serving per week was associated with less weight gain (-0.4 kg; 95% confidence interval [CI] = -0.6, -0.2). Conversely, relative to no change, an increase in sugar-sweetened soda by more than 1 serving per week was associated with a 0.3-kilogram (95% CI = 0.2, 0.5) increase in weight. An increase of 1 serving per day of sugar-sweetened soda was associated with a 1.0 kg (95% CI = 0.7, 1.2; P < .001) increase in weight. The results for waist circumference were similar. CONCLUSIONS: Moderate changes in consumption of sugar-sweetened soda over a 2-year period were associated with corresponding changes in weight and waist circumference among Mexican women.

Association of secondhand smoke exposure with pediatric invasive bacterial disease and bacterial carriage: a systematic review and meta-analysis.

BACKGROUND: A number of epidemiologic studies have observed an association between secondhand smoke (SHS) exposure and pediatric invasive bacterial disease (IBD) but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis), Haemophilus influenzae type B (Hib), and Streptococcus pneumoniae (S. pneumoniae). METHODS AND FINDINGS: Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs) were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52-2.69) for invasive meningococcal disease, 1.21 (95% CI 0.69-2.14) for invasive pneumococcal disease, and 1.22 (95% CI 0.93-1.62) for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19-2.36) for N. meningitidis, 1.66 (95% CI 1.33-2.07) for S. pneumoniae, and 0.96 (95% CI 0.48-1.95) for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72-6.13). CONCLUSIONS: When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be associated with invasive meningococcal disease. The epidemiologic evidence is currently insufficient to show an association between SHS and invasive Hib disease or pneumococcal disease. Because the burden of IBD is highest in developing countries where SHS is increasing, there is a need for high-quality studies to confirm these results, and for interventions to reduce exposure of children to SHS.