Gomez-Reino_edit.qxp 1/10/07 12:16 Page 18
Rheumatoid Arthritis
Switching Tumour Necrosis Factor Inhibitors in the
Treatment of Chronic Arthropathies
a report by
Loreto Carmona
1
and Juan J Gómez-Reino
2
1. Research Unit, Spanish Society of Rheumatology; 2. Rheumatology Service and Department of Medicine,
Hospital Clínico Universitario, Medical School, Universidad de Santiago de Compostela
New biologic therapies for the treatment of rheumatoid arthritis (RA) pharmacokinetics and mechanisms of action.
7
The half-life of
are directed to mediators involved in the pathogenesis of the disease. etanercept is three days, of infliximab 10 days and of adalimumab 13
Robust responses to treatment with the tumour necrosis factor (TNF) days. These half-life differences may translate into differences in the
inhibitors adalimumab, etanercept and infliximab have improved the extent of TNF neutralisation. In addition, the two monoclonal
outcomes of RA patients:
1
in early RA, biologic-free remission and antibodies – infliximab and adalimumab – have strong affinity for TNF,
drug-free remission are now achievable,
2,3
and in both early and which may increase the percentage of neutralised TNF molecules. In
established RA treated with TNF inhibitors, two-thirds of patients addition, complexes formed of anti-TNF antibodies and monomeric
achieve meaningful clinical responses. However, one-third do not and trimeric soluble and membrane-associated TNF are far more stable
respond and, furthermore, a number of patients who initially respond than those formed of the soluble TNF receptor etanercept. Finally, the
go on to develop acquired drug resistance or gradual drug failure.
4
In monoclonal antibodies bind only TNF, whereas etanercept also binds
addition, some patients have to discontinue the biologic treatment due lymphotoxin. Thus, in the absence of therapeutic alternatives in RA,
to adverse events. All in all, the three-year retention rate of TNF switching TNF inhibitors in patients failing on a first biologic agent has
inhibitors is around 65%.
5
been considered a reasonable therapeutic approach.
Although all TNF inhibitors have similar efficacy in treating RA,
6
they In a survey among US rheumatologists,
8
over 94% reported switching
differ in terms of their effectiveness with regard to other rheumatic patients from one TNF inhibitor to another due to inadequate response
diseases. In contrast to the monoclonal antibodies, etanercept is not or side effects. Additionally, guidelines from the Spanish Society of
effective in the treatment of granulomatous disorders such as Crohn’s Rheumatology
9
and the French Society of Rheumatology
10
recommend
disease, Wegener’s granulomatosis and sarcoidosis. In RA, reports, the use of any TNF inhibitor in patients with inadequate response to a
case series and observational studies indicate that some patients may previous one. Nevertheless, the UK National Institute for Health and
respond to one but not to another TNF inhibitor. This is partially Clinical Excellence (NICE) has concluded that any diminution in efficacy
supported by data showing that TNF inhibitors differ in terms of their between first and second TNF inhibitor would take the cost-
effectiveness of second use outside the acceptable range.
11
Loreto Carmona works in the Research Unit at the
Spanish Society of Rheumatology. Previous positions
Despite the biologic rationale for switching TNF inhibitors, there are no
include Clinical Researcher in various epidemiology units conclusive data regarding the outcomes of switching; furthermore,
and Consultant Rheumatologist. She has also worked for
alternatives to switching exist in RA. These include: combination
the Spanish Medicines Agency. Dr Carmona has led many
epidemiological projects in the field of rheumatic diseases
therapy with traditional disease-modifying antirheumatic drugs
in Spain, and in 2003 she helped to create the
(DMARDs); combination of TNF inhibitors with DMARDs other than
infrastructure of a strategic research centre for the
Spanish Society of Rheumatology. She was trained as a
methotrexate; and the new, recently approved biologics rituximab and
rheumatologist at Hospital de la Princesa in Madrid, and as a clinical epidemiologist at abatacept, which have distinct mechanisms of action. The efficacy of
the University of California at San Francisco (UCSF). At UCSF, she obtained a post-
TNF inhibitors has been also shown in other rheumatic diseases,
doctoral fellowship to work with the Arthritis Research Group.
including spondyloarthropathies (SpAs) and juvenile idiopathic
arthritis. In these conditions, there is only limited information on
Juan J Gómez-Reino is based at the Hospital Clinico
Universitario at the Universidad de Santiago de
switching TNF inhibitors.
Compostela, Santiago, which is the regional referral
centre for rheumatology. He was formerly Chief of the
Department of Research and Section of Rheumatology at
Switching Tumour Necrosis Factor Inhibitors in
Hospital Doce de Octubre, Madrid. The focus of Professor Rheumatoid Arthritis
Gómez-Reino’s clinical practice is rheumatoid arthritis,
To June 2007, there were 32
12–43
relevant reports in the literature
spondyloarthrophathies and connective tissue diseases.
His main interest is in chronic inflammatory arthropathies
on switching from one to a second TNF inhibitor in patients
and his experimental research is in the genetics of complex diseases, the effect of
who experienced treatment failure. Most reports were observational
adypokines on chondrocyte function and models of arthritis in gene ‘knockout’ mice. He
has authored or co-authored original articles and papers on topics such as rheumatoid
studies (n=19), case series (n=10) or prospective cohorts from
arthritis, spondyloarthritis and other rheumatology-specific disorders. Professor Gómez- biologic registries (n=3). Twenty-nine reports refer to RA
Reino completed his medical and doctor of philosophy degrees at the University of Madrid
patients,
12–22,25–40,42,43
and four to chronic arthropathies. Thirteen
and his post-graduate training in internal medicine and rheumatology at the State
University of New York, Stony Brook, New York.
studies
12,14,16,18,20,22,24,27,29,32,34,37,41
give an account of the switch
from a monoclonal anti-TNF antibody to etanercept,
E: juan.gomez-reino.carnota@sergas.e
12
12,16,18,22,23,26–28,33,35,39,44
from etanercept to a monoclonal anti-TNF
18 © TOUCH BRIEFINGS 2007
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99