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Anti-TNF treatment of chronic arthritis in clinical practice. New assessment method and predictors of efficacy and tolerability.

Kristensen, Lars Erik LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:32.
Abstract
Abstract

Treatment of chronic inflammatory arthritis has undergone major changes over the past years following introduction of targeted biological therapies. Tumour necrosis factor (TNF) blocking therapy has been the most important biological treatment of chronic arthritis to date.

The overall objective of this thesis was to develop a new assessment method of efficacy of biological therapy in clinical practice. Further objectives were to study efficacy and tolerability and predictors thereof in anti-TNF treated patients with chronic arthritis in an open study setting. The thesis is based on four studies of patients with established rheumatoid arthritis (RA) and one study of patients with psoriatic arthritis (PsA).... (More)
Abstract

Treatment of chronic inflammatory arthritis has undergone major changes over the past years following introduction of targeted biological therapies. Tumour necrosis factor (TNF) blocking therapy has been the most important biological treatment of chronic arthritis to date.

The overall objective of this thesis was to develop a new assessment method of efficacy of biological therapy in clinical practice. Further objectives were to study efficacy and tolerability and predictors thereof in anti-TNF treated patients with chronic arthritis in an open study setting. The thesis is based on four studies of patients with established rheumatoid arthritis (RA) and one study of patients with psoriatic arthritis (PsA).

Patients included in the five studies were monitored according to a standardized clinical protocol of the South Swedish Arthritis Treatment Group (SSATG) developed at the Department of Rheumatology in Lund. The protocol included baseline characteristics such as diagnosis, disease duration, previous and ongoing disease modifying antirheumatic drugs (DMARDs), treatment start and termination. In addition efficacy measures used for calculating treatment response, i.e. EULAR and ACR response criteria, were collected at fixed time-points. Data were prospectively registered from March 1999.

To overcome shortcomings of previous methods for reporting response data from long term observational cohorts, LUNDEX (LUND Efficacy indeX) was designed. LUNDEX adjusted response data combines the proportion of patients fulfilling a selected response criterion with the proportion of patients adhering to a particular therapy. LUNDEX applied on RA and PsA patients proved to be a valuable tool for evaluating drug efficacy in observational studies. It has the advantage of integrating both clinical response as well as adherence to therapy in a composite score.

Predictors of drug survival in RA and PsA were studied using Cox regression models. The models showed that the risk for premature treatment termination was higher in infliximab compared to etanercept treated patients. Also, regression analysis showed that patients with higher baseline CRP-levels and concomitant MTX treatment had better overall treatment continuation.

Good response to anti-TNF therapy in RA was associated with concomitant MTX or other DMARD treatment as well as low disability. Moreover, RA patients who failed their first course of anti-TNF treatment, showed response rates during second anti-TNF treatment course in the range of the initial treatment. In contrast, response to a third anti-TNF treatment was markedly reduced, suggesting that other treatment options should be tried.

In conclusion, LUNDEX proved to be a practical and a potentially universal tool, valuable for assessing drug response in an open study setting. Important predictors of efficacy and tolerability of anti-TNF treatment were identified. (Less)
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author
supervisor
opponent
  • Prof Westhovens, Rene, Catholic University of Leuven, Belgium
organization
publishing date
type
Thesis
publication status
published
subject
keywords
response, drug survival, psoriatic arthritis, Arthritis, rheumatoid arthritis, adverse events, TNF antagonists
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:32
pages
95 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Föreläsningssalen Reumatologiska kliniken
defense date
2008-04-04 09:00
ISSN
1652-8220
ISBN
978-91-85897-85-8
language
English
LU publication?
yes
id
3342fb5a-71b3-4135-8c00-26437cc36dda (old id 1049303)
date added to LUP
2008-03-19 12:59:56
date last changed
2016-09-19 08:44:48
@phdthesis{3342fb5a-71b3-4135-8c00-26437cc36dda,
  abstract     = {Abstract<br/><br>
Treatment of chronic inflammatory arthritis has undergone major changes over the past years following introduction of targeted biological therapies. Tumour necrosis factor (TNF) blocking therapy has been the most important biological treatment of chronic arthritis to date.<br/><br>
The overall objective of this thesis was to develop a new assessment method of efficacy of biological therapy in clinical practice. Further objectives were to study efficacy and tolerability and predictors thereof in anti-TNF treated patients with chronic arthritis in an open study setting. The thesis is based on four studies of patients with established rheumatoid arthritis (RA) and one study of patients with psoriatic arthritis (PsA). <br/><br>
Patients included in the five studies were monitored according to a standardized clinical protocol of the South Swedish Arthritis Treatment Group (SSATG) developed at the Department of Rheumatology in Lund. The protocol included baseline characteristics such as diagnosis, disease duration, previous and ongoing disease modifying antirheumatic drugs (DMARDs), treatment start and termination. In addition efficacy measures used for calculating treatment response, i.e. EULAR and ACR response criteria, were collected at fixed time-points. Data were prospectively registered from March 1999. <br/><br>
To overcome shortcomings of previous methods for reporting response data from long term observational cohorts, LUNDEX (LUND Efficacy indeX) was designed. LUNDEX adjusted response data combines the proportion of patients fulfilling a selected response criterion with the proportion of patients adhering to a particular therapy. LUNDEX applied on RA and PsA patients proved to be a valuable tool for evaluating drug efficacy in observational studies. It has the advantage of integrating both clinical response as well as adherence to therapy in a composite score. <br/><br>
Predictors of drug survival in RA and PsA were studied using Cox regression models. The models showed that the risk for premature treatment termination was higher in infliximab compared to etanercept treated patients. Also, regression analysis showed that patients with higher baseline CRP-levels and concomitant MTX treatment had better overall treatment continuation. <br/><br>
Good response to anti-TNF therapy in RA was associated with concomitant MTX or other DMARD treatment as well as low disability. Moreover, RA patients who failed their first course of anti-TNF treatment, showed response rates during second anti-TNF treatment course in the range of the initial treatment. In contrast, response to a third anti-TNF treatment was markedly reduced, suggesting that other treatment options should be tried. <br/><br>
In conclusion, LUNDEX proved to be a practical and a potentially universal tool, valuable for assessing drug response in an open study setting. Important predictors of efficacy and tolerability of anti-TNF treatment were identified.},
  author       = {Kristensen, Lars Erik},
  isbn         = {978-91-85897-85-8},
  issn         = {1652-8220},
  keyword      = {response,drug survival,psoriatic arthritis,Arthritis,rheumatoid arthritis,adverse events,TNF antagonists},
  language     = {eng},
  pages        = {95},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Anti-TNF treatment of chronic arthritis in clinical practice. New assessment method and predictors of efficacy and tolerability.},
  volume       = {2008:32},
  year         = {2008},
}