NEWS - Nothing untoward on TNF antagonists emerging from British biologics register

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Nothing untoward on TNF antagonists emerging from British biologics register

Rheumawire

Apr 22, 2005

Zosia Chustecka

Birmingham, UK - The data accumulated by the British Society of Rheumatology

Biologics Register (BSRBR), which monitors most of the patients in the UK

taking TNF antagonists, has not found anything untoward, and the patterns

that are emerging for infection and mortality rates are in line with what

can be expected in the patient population being treated. This was the

message coming out of several presentations at the society's annual meeting

this week.

The BSRBR researchers, led by Prof Alan Silman and Dr Deborah Symmons

(University of Manchester, UK), are also collecting data on a set of control

patients who have rheumatoid arthritis (RA) but are not being treated with

biologic therapies, and so far 1534 such patients have enrolled.

Follow-up involves participation from both patients and their consultant

rheumatologists. Patients are required to keep a diary and fill in a

questionnaire every 6 months, while consultants are required to fill in

questionnaires every 6 months for the first 3 years and then annually for

the next 2 years. Details are sought on serious adverse events, including

death, hospitalization, disability and/or significant loss of function,

congenital malformation, and any life-threatening reactions. In addition,

all of the patients are flagged for malignancy and mortality by the Office

of National Statistics (ONS).

Dr Kate (Manchester University) presented new data on mortality at

the meeting.[1] She emphasized that the results were preliminary as they

covered only the first few years of use of TNF antagonists, but so far the

data show an increased mortality in RA patients taking TNF antagonists when

compared with the general population; however, the increase is in line with

what would be expected in a population of RA patients on the basis of data

compiled from other sources.

's analysis involved 4617 patients (59% on infliximab, 32% on

etanercept, and 9% on adalimumab), of whom 77% were females. The median

length of follow-up was 1.4 years, which gives 7013 patient-years of

follow-up. A total of 86 deaths were recorded by the ONS, giving a rate of

12.3/1000 patient-years. The causes of death were recorded as follows:

cardiovascular disease (29%), malignancy (17%), infection (16%), pulmonary

disease (12%), and RA itself (18%).

The standardized mortality ratio (SMR, calculated as observed/expected

number of deaths) was 1.5 for males (95% CI 1.0-2.2) and 1.4 (95% CI

1.1-1.8) for females. " This is broadly similar to what has been reported

previously for rheumatoid arthritis patients, " said, noting in

particular a paper by Symmons et al in 1998.[2]

Dr Will Dixon (University of Manchester) presented data on serious infection

rates from a total of 6388 patients (44.9% on infliximab, 40.7% on

etanercept, and 14.3% on adalimumab) and also calculated the results in

terms of patient-years of follow-up.[3]

" So far, we have seen no important differences between the anti-TNF agents, "

he said. The commonest sites for infections were the lower respiratory

tract, skin and soft tissue, bone and joint, and urinary tract.

However, Dixon noted that " total intracellular bacterial infection rates

were broadly similar between etanercept and infliximab but may be higher

than for adalimumab-treated patients and in RA controls. " In addition, he

noted that serious infection with Salmonella was reported only in patients

on etanercept (3 cases: 2 septic arthritis and 1 gastroenteritis). The data

support the theory that tuberculosis may be more common with infliximab than

with etanercept (2.3 and 0.8 per 1000 patient-years, respectively), he said,

and this study confirms previous findings that the pattern of TB in

biologics-treated patients is unusual: from 11 cases of TB, 4 (36%) were

localized pulmonary but 7 (64%) were extrapulmonary.

One question that remains unanswered is how the infection rate in RA

patients taking biologics compares with RA patients not on these drugs,

Dixon commented. The BSRBR had only 1405 control RA patients at the time of

analysis, but a comparison of the rates in both groups shows they are

similarhowever, these rates have not been adjusted. Dixon noted that the

rate of lower-respiratory-tract infections appeared to be lower in

TNF-inhibitor-treated patients than in controls, but he remarked that there

were more smokers among the controls and also that a respiratory-tract

infection is a contraindication to TNF-inhibitor treatment. Also, there was

only 1 skin infection in the control group, compared with 150 cases in the

biologics patients, so " maybe TNF plays a role in limiting the spread of

infection, " Dixon speculated.

Sources

1. K, Hyrich K, et al. Mortality among RA patients

receiving anti-TNF therapy in the United Kingdom: results from the BSR

biologics registry. Rheumatology 2005; 44 (supplement 1);i23.

2. Symmons DP, MA, DL, Prior P. Longterm

mortality outcome in patients with rheumatoid arthritis: early presenters

continue to do well.

J Rheumatol. 1998; 25:1072-1077.

3. Dixon W, Hyrich K, et al. Serious infection rates in

patients receiving biologic therapy in the United Kingdom: results from the

BSR Biologics Register. Rheumatology 2005; 44 (supplement 1):i11.

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Mayo Clinic in Rochester

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