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Abstract
Background Anti-TNF drugs are an effective therapy for patients (pts) with rheumatoid arthritis (RA) but are associated with an increased incidence of serious infectious events (SIEs). We have previously identified baseline (BL) age and comorbidity as risk factors for SIEs in certolizumab pegol (CZP)-treated RA pts.1
Objectives To identify RA pts at high/low risk of developing SIEs during long-term CZP treatment, using a BL age-adjusted comorbidity index (AACI).
Methods CZP safety data from anti-TNF naïve patients were pooled from the RAPID1 and RAPID2 randomized controlled trials (NCT00152386/NCT00160602) and their open-label extensions (NCT00175877/NCT00160641). Post-hoc analyses of SIEs with onset after the first CZP dose and ≤84 days after the last CZP dose or withdrawal are presented. Pts' AACI was based on the Charlson index: it included medically-treated comorbidities (diabetes mellitus, chronic obstructive pulmonary disease/asthma, cardiac disorder, hypertension, lipidemia, transient ischemic attack or cerebrovascular disorder; each with score=1) and the resulting score was increased by 1 for each decade over the age of 40 years (yrs) at BL.2 Incidence rates (IRs) of SIEs were calculated per 100 pt-yrs (PY), with 95% confidence intervals (CIs); time at risk = time from first CZP dose to the first SIE, or the total CZP time at risk for pts without SIEs. A multivariate Cox proportional hazards model (selection criteria: p≤0.25) was used to estimate the relative risk (hazard ratio [HR]) of BL pt covariates to the first SIE. BL covariates analyzed were AACI (≤1; 2; 3; ≥4), BMI (<20; 20–30; >30 kg/m2), DAS28(CRP), disease duration (<2; ≥2 yrs), HAQ-DI, joint erosion score, MTX dose (≤15; >15 mg/week) and systemic steroid use (Yes; No). High/low risk pt groups were defined based on co-occurrence of the highest/lowest risk categories in the Cox model, respectively.
Results 201/1506 anti-TNF naïve CZP pts reported ≥1 SIE over ∼6 yrs of CZP treatment (IR 3.66/100 PY, 95% CI 3.17–4.21; total exposure 5778.6 PY). Overall, the observed IR of SIEs increased with AACI (Figure 1A). According to the Cox model, AACI ≥3 was a risk factor for SIEs; AACI=2, BL systemic steroid use, disease duration <2 yrs and DAS28(CRP) also contributed to SIE risk (Figure 1B). 195 pts (12.9%) were identified as “low risk” at BL (AACI≤1, no systemic steroid use) and 141 pts (9.4%) as “high risk” (AACI≥4, systemic steroids used). Over time, high risk pts reported more SIEs than low risk pts; across all pt groups, the observed IR was highest in the first yr of CZP treatment (Figure 1C). Results should be interpreted with caution, as it was not possible to compare the absolute risk of SIEs between CZP and placebo pts with similar AACI, due to limited placebo exposure.
Conclusions In RA pts treated with CZP, higher age-adjusted comorbidity index was associated with a greater relative risk of SIEs. The stratification of RA pts at BL using a global risk score may help clinicians to better assess the risks and benefits of long-term CZP treatment.
Haraoui B. Arthritis Rheum 2014;66:S201;
Koppie T. Cancer 2008;112:2384–92
Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance.
Disclosure of Interest J. R. Curtis Grant/research support from: Roche/Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, Consultant for: Roche/Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, K. Winthrop Grant/research support from: BMS, Consultant for: UCB Pharma, Pfizer, BMS, Eli Lilly, AbbVie, Roche, M. de Longueville Employee of: UCB Pharma, C. O'Brien Employee of: UCB Pharma, M. N. Ndlovu Employee of: UCB Pharma, B. Haraoui Grant/research support from: Abbott, Amgen, BMS, Janssen, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, Amgen, BMS, Janssen, Pfizer, Roche, UCB Pharma, Speakers bureau: Abbott, Amgen, BMS, Janssen, Pfizer, Roche, UCB Pharma