ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2140

Drug Specific Risk and Associated Factors for Vasculitis-like Events in Patients Exposed to Tumour Necrosis Factor-α Inhibitor Therapy: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Meghna Jani1, William G Dixon2, Lianne Kearsley-Fleet3, Ian N. Bruce4,5, Hector Chinoy6,7, Anne Barton6,8, Mark Lunt9, Kath Watson3, Deborah P.M. Symmons1, Kimme L. Hyrich3 and on behalf of the BSRBR-RA, 1Centre for Musculoskeletal Research, University of Manchester, Arthritis Research UK Centre for Epidemiology, Manchester, United Kingdom, 2Manchester Academic Health Sciences Centre, Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, United Kingdom, 3Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, United Kingdom, 4Stopford Building, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom, 5Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester, United Kingdom, 6Centre for Musculoskeletal Research, University of Manchester, Manchester, United Kingdom, 7NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, Manchester, United Kingdom, 8NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust and University of Manchester, Manchester Academy of Health Sciences, Manchester, United Kingdom, 9Arthritis Research UK Centre for Epidemiology, Manchester, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy IV: Safety of Targeted Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

The association between TNF inhibitors (TNFis) and vasculitis-like events, possibly secondary to induction of autoantibodies, has been well reported. However, the incidence, drug-specific differences and factors associated have been poorly characterised. The aims of this study were to (i) compare the drug specific risk of vasculitis-like events in TNFi treated RA patients to those receiving non-biologic (nb)DMARDs and (ii) assess factors associated with the event.

Methods:

The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective cohort study assessing the safety of biologics. This analysis included two cohorts recruited between 2001-2014: (i) patients starting first TNFi (adalimumab, etanercept, infliximab, certolizumab) (ii) biologic-naïve comparison cohort receiving nbDMARDs. To calculate drug-specific risk biologic-naïve patients at baseline on first TNFi only were included. Additional information from consultants was sought for events. Patients with baseline systemic vasculitis were excluded. The risk of an event was compared between the two cohorts using Cox proportional-hazard models, adjusted using deciles of propensity scores (PD). Events were attributed to TNFi therapy if they occurred within 90 days of being on drug. Follow-up was censored at first event, switching to another biologic, death, last returned clinical follow-up or 30/11/2014, whichever came first. A sensitivity analysis was performed excluding patients who had a possible secondary vasculitis cause (e.g. infection), on other medications associated with vasculitis-like events or known baseline nailfold vasculitis.

Results:

There were 94 incident cases: 14 in 3640 nbDMARD patients and 80 in 12,385 first TNFi-treated subjects, with 19,681 and 49,678 patient years of follow up generating crude incidence rates of 7/10,000 and 16/10,000 person years respectively (Table). After adjusting for PD, the hazard ratio of vasculitis-like events in patients on TNFi vs. nbDMARD was 1.03 (95% CI 0.51-2.09). Drug specific hazard ratios were highest in the etanercept and infliximab patients, however following adjustment was not significant (Table). Factors associated with lower rates included baseline MTX use (HR 0.8, 95% CI 0.74-0.88), SSZ (HR 0.58, 95% CI 0.51-0.66) or LEF (HR 0.66, 95% CI 0.54-0.77). Other variables associated with the outcome included male gender (HR 1.49, 95% CI 1.01-2.21), baseline DAS28 score (HR 1.42, 95% CI 1.20-1.68), disease duration (HR 1.02, 95% CI 1.01-1.04 per year), RF+ status (HR 1.79 (95% CI 1.16-2.75) and baseline HAQ (HR 1.63, 95% CI 1.18-2.26).

Table. Patient characteristics and risk of first vasculitis-like event on first drug

 

nbDMARD

(n=3640)

    TNFi

(n=12,385) 

 Infliximab

 (n=3,285) 

 Adalimumab 

   (n=4,230)

 Etanercept 

 (n=4,306)

 Certolizumab 

     (n=564)

Age, mean (SD)

60 (12)

56 (12)

55 (12)

56 (12)

56 (12)

56 (12)

Follow up per subject, years: median (IQR)

6.0(3-8)

5.3 (2-8)

4.9 (2-9)

5.3 (2-7)

6.3 (3-9)

1.4 (1-2)

Main analysis: Risk of vasculitis-like events between nbDMARD and TNFi (all vasculitis events)

Number of vasculitis-like events, n

14

80

26

17

37

0

Crude incidence rate of vasculitis-like events per

10, 000 person-years (95%-CI)

7 (4-12)

16 (13-20)

20 (14-30)

10 (6-16)

18 (13-25)

–

Unadjusted hazard ratio (95%-CI)

Referent

2.13 (1.21-3.77)*

2.66 (1.41-5.01)*

1.52 (0.78-2.96)

2.91 (1.60-5.29)*

–

Age- and gender adjusted hazard ratio (95%-CI)

Referent

2.33 (1.31-4.14)*

2.89 (1.50-5.49)*

1.64 (0.80-3.20)

3.27 (1.75-5.9)*

–

Propensity score adjusted hazard ratio (95%-CI) †

Referent

1.03 (0.51-2.09)

1.18 (0.54-2.56)

0.84 (0.39-1.77)

1.37 (0.64-2.79)

–

Sensitivity analysis (excluding events with possible secondary trigger)

Number of vasculitis-like events, n (%)

13

67

22

16

29

0

Crude incidence rate of vasculitis-like events per

10, 000 person-years (95%-confidence interval)

6 (3-11)

13 (10-17)

18 (12-27)

10 (6-16)

14 (10-20)

–

–        Unadjusted hazard ratio (95%-CI)

Referent

1.93 (1.06-3.51)*

2.47 (1.26-4.82)*

1.56 (0.78-3.12)

2.31 (1.22-4.37)*

–

–        Age- and gender adjusted hazard ratio (95%-CI)

Referent

2.07 (1.13-3.78)*

2.64 (1.34-5.19)*

1.66 (0.83-3.34)

2.51 (1.31-4.78)*

–

–        Propensity score adjusted hazard ratio (95%-CI) †

Referent

0.89 (0.42-1.86)

1.04 (0.46-2.36)

1.01 (0.46-2.19)

0.8 (0.37-1.77)

–

* p<0.05

† Fully adjusted model by propensity score consisting of age, gender, year of recruitment, DAS28, disease duration, rheumatoid factor, HAQ, steroid use, baseline DMARD use, smoking and comorbidities score

Conclusion:

In this large UK study, the absolute risk of vasculitis-like events in both groups was low. There were no significant differences in risk between TNFi agents after adjustment. Baseline use of MTX, SSZ and LEF were associated with lower rates.

Disclosure: M. Jani, Pfizer Inc, 8,Abbvie, UCB, 5; W. G. Dixon, None; L. Kearsley-Fleet, None; I. N. Bruce, Bristol-Myers Squibb, 2; H. Chinoy, Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, 5,Novartis, Janssen, Pfizer, UCB, Abbvie, Celgene, Servier, Roche, MSD, and aTyr, 2; A. Barton, Eli-Lilly, Pfizer, Abbvie, 2; M. Lunt, None; K. Watson, None; D. P. M. Symmons, None; K. L. Hyrich, None.

To cite this abstract in AMA style:

Jani M, Dixon WG, Kearsley-Fleet L, Bruce IN, Chinoy H, Barton A, Lunt M, Watson K, Symmons DPM, Hyrich KL. Drug Specific Risk and Associated Factors for Vasculitis-like Events in Patients Exposed to Tumour Necrosis Factor-α Inhibitor Therapy: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/drug-specific-risk-and-associated-factors-for-vasculitis-like-events-in-patients-exposed-to-tumour-necrosis-factor-i%c2%b1-inhibitor-therapy-results-from-the-british-society-for-rheumatology-biologic/. Accessed .

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