Session Information
Session Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis
Session Type: Abstract Submissions (ACR)
Background/Purpose
Rheumatoid arthritis (RA) is associated with elevated cardiovascular (CV) risk not explained by traditional risk factors. Increased CV risk may develop prior to the onset of arthritis. Amongst RA patients Shared Epitope (SE) positivity is associated with increased CV mortality but it is unclear if this is mediated by inflammation. Observational studies suggest that TNF-inhibition improves endothelial dysfunction and lowers CV risk but RCT data are lacking. HEART-RA is a single-site RCT evaluating the effect of Humira upon endothelial function in ACPA positive RA.
Methods
ACPA positive RA patients with moderate disease activity were enrolled in a 24-week trial of Humira versus placebo on a background of usual care undergoing assessments of disease activity and endothelial function (reactive hyperaemic index – RHI) at baseline, 2, 4, 12 and 24 weeks. Serum lipids were evaluated when deemed appropriate by the treating clinician. Improvements RHI in Humira and placebo arms were compared by t test. Secondary analysis evaluated influences upon RHI by univariate analysis and multivariate time-series regression modelling.
Results
23 subjects included 9 early (<6months) and 14 established RA underwent a total 138 assessments. 1 patient carried none, 10 one and 12 two SE. 12 patients (4 Humira and 3 placebo) withdrew after week 12 and were assessed open label at 24 weeks. HDL was available for 28 and LDL for 24. There were non-significant trends to greater RHI improvements in the Humira arm. Secondary analysis found better RHI in patients currently receiving Humira distinct from more general negative effects of higher disease activity and SE dose. Paradoxically ever-smokers had better RHI. Limited data suggested positive effects from HDL and negative from LDL.
Conclusion
Several disease-specific factors appear to contribute to endothelial dysfunction in RA. RHI is clearly better in patients receiving Humira distinct from the broader effects of disease activity. The paradoxical effect of smoking is not consistent with previous studies and is likely due to the small number of patients. However, negative effects of the SE are consistent with previous work. Furthermore, the effect appears to be quite distinct from inflammatory mechanisms seen in RA and introducing the possible role of antigen processing and lipid transport with implications for subjects with Pre-RA and therapies that that adversely influence lipids.
| Raw | Adjusted | |||||
| Input Variables | Mean RHI | Mean RHI | Difference | t test p value | Difference | Adjusted p value |
| Humira vs No Humira | 2.23 | 2.11 | 0.12 | 0.016 | 0.19 | 0.041 |
| 3VDAS28CRP (<3.88 vs >3.88) | 2.22 | 2.00 | 0.22 | 0.016 | 0.17 | 0.056 |
| Shared Epitope (2 vs 0 or 1 copy) | 2.20 | 2.04 | 0.16 | 0.080 | 0.25 | 0.045 |
| Smoking (Ever versus Never) | 2.20 | 1.79 | 0.24 | 0.001 | 0.44 | 0.004 |
| Established vs Early RA | 2.21 | 1.97 | 0.24 | 0.010 | 0.20 | 0.119 |
| HDL Choilesterol (>1.20 vs <1.20) | 2.23 | 2.06 | 0.17 | 0.448 | Insufficient data | |
| LDL Cholesterol (<3.00 vs >3.00) | 2.13 | 2.07 | 0.06 | 0.226 | Insufficient data |
Disclosure:
S. Oakley,
Abbvie,
2,
UCB,
9,
Roche Pharmaceuticals,
9,
Janssen Pharmaceutica Product, L.P.,
9,
Pfizer Inc,
9;
N. Esmaili,
Abbvie Laboratories,
2;
G. Major,
Abbvie,
2,
Abbvie,
9;
D. Mathers,
Abbvie,
2,
Pfizer Inc,
9,
BMS,
9,
Abbvie,
9,
UCB,
9,
Janssen Pharmaceutica Product, L.P.,
9;
S. Ratnarajah,
Abbvie,
2;
J. van der Kallen,
Abbvie,
2,
Amgen,
8;
M. Collins,
Abbvie,
2,
BMS,
9,
Roche Pharmaceuticals,
9,
Abbvie,
9;
M. Toh,
Abbvie,
2;
J. Glass,
Abbvie,
2.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-randomised-controlled-trial-evaluating-the-effect-of-humira-upon-endothelial-function-in-acpa-positive-rheumatoid-arthritis-ae-an-interim-analysis/