Analysis of the safety profile of the TNF-alpha antibody infliximab based on the pooled data of 3 German post-marketing surveillance studies with 1,075 patients suffering from rheumatoid arthritis or Crohn's disease

We planned to evaluate the safety profile of the TNF-alpha antagonist infliximab (IFX) in a large population of patients with rheumatoid arthritis (RA) or Crohn's disease (CD) treated with IFX under routine conditions in the post-marketing phase. Therefore, we pooled the data of 3 independently performed post-marketing surveillance studies (PMSs, 2 studies with 309 and 107 CD patients, respectively, and 1 study with 659 RA patients), amounting to a total number of 1,075 patients treated at 255 study sites. All PMSs were designed as prospective non-experimental and non-controlled multicenter observational studies. Adverse events (AEs) were classified according to WHO-ADRT system organ classes (SOC) and preferred terms.

On average, the CD population was distinctly younger, had a higher proportion of men and was treated with higher doses than the RA population. In total, the patients (67% women) had a mean age of 45.4±15.4 years (range: 11–96) and received on average 3.3±1.2 IFX infusions (range: 1–6) at a mean dose of 4.0±1.0mg/kg BW per infusion (range: 1–10). The overall incidence of AEs was 18.4%, the incidence of AEs with an at least possible relationship to IFX (related AEs) was 14.9%, and the one of serious AEs (SAEs) was 3.5%. There were no relevant differences among the 3 studies. Related AEs with an incidence of at least 1% in any of the PMSs are tabulated. 20 patients (1.9%) experienced related SAEs (mostly hypersensitivity reactions and deterioration of the underlying disease). One patient developed tuberculosis and in 4 patients neoplasms were diagnosed during the observation period. One death was documented (apoplexy unrelated to IFX). AEs leading to discontinuation of treatment were reported for 37 patients (3.4%).

The analysis of the safety profile in terms of frequency and nature of AEs occurring under everyday practice conditions were consistent with the current knowledge of IFX and did not reveal any new or alarming information. The drop-out rate due to AEs was lower than in clinical studies. Thus, the results of this pooled safety analysis supported the routine use of infliximab also in a patient population more heterogeneous than in experimental clinical studies.

WHO-ADRT SOC	PMS RA	PMS CD I	PMS CD II	Total
	n (%)	n (%)	n (%)	n (%)
All patients with related AEs	90 (13.7%)	55 (17.8%)	15 (14.0%)	160 (14.9%)
Respiratory system disorders	33 (5.0%)	10 (3.2%)	2 (1.9%)	45 (4.2%)
Body as a whole - general disorders	21 (3.2%)	10 (3.2%)	5 (4.7%)	36 (3.3%)
Skin and appendages disorders	21 (3.2%)	10 (3.2%)	5 (4.7%)	36 (3.3%)
Resistance mechanism disorders	10 (1.5%)	11 (3.6%)	2 (1.9%)	23 (2.1%)
Gastrointestinal system disorders	8 (1.2%)	12 (3.9%)	4 (3.7%)	24 (2.2%)
Urinary system disorders	7 (1.1%)	4 (1.3%)	0	11 (1.0%)
Central & peripheral nervous system disorders	2 (0.3%)	9 (2.9%)	1 (0.9%)	12 (1.1%)
Cardiovascular disorders, general	7 (1.1%)	3 (1.0%)	0	10 (0.9%)
Musculo-skeletal system disorders	3 (0.5%)	7 (2.3%)	1 (0.9%)	11 (1.0%)
Heart rate and rhythm disorders	4 (0.6%)	3 (1.0%)	0	7 (0.7%)

Schlüsselwörter

Crohn's disease - Infliximab - TNF-alpha - post marketing surveillance - rheumatoid arthritis - safety profile