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Beyond the scope of erosive osteoarthritis of the interphalangeal finger joints: new insights from epidemiological, clinical and imaging based studies

RUTH WITTOEK UGent (2010)
abstract
Osteoarthritis of the hand (HOA) is a common musculoskeletal disorder characterized by degradation of cartilage and changes in subchondral bone. The disease has a heterogeneous character and several subsets have been proposed. One of the subsets is affecting the interphalangeal (IP) finger joints: 2 subtypes are recognized, the erosive and non-erosive type. The diagnosis of erosive osteoarthritis of the IP finger joints (EOA) is based on the presence of radiographic subchondral erosions which lead to deformities and sometimes bony ankylosis of the joint. The higher clinical burden and worse outcome than non-erosive IP finger joint OA is apparent from daily clinical practice. Although the radiographic features of EOA are well characterized, the etiopathogenesis of the disease and etiology responsible to drive the ‘inflammatory clinical picture’ of EOA are less well understood. The aim of this work described in this thesis is to contribute to the knowledge on EOA in several aspects, in order to improve the approach to patients with several subtypes of HOA. In addition, we aimed to situate the level of pain and functional impairment in EOA in relation to other rheumatic disorders. With the use of imaging tools, we tried to identify differences in anatomic basis between EOA and non-erosive OA. Ultimately, the better knowledge and recognition of the disease and its subtypes may contribute to adequate treatment. The first part of this thesis studied the differences in functional impairment and pain between several groups of HOA, depending on the presence of erosive disease, and patients with inflammatory arthritis of the finger joints. Functional impairment was measured by the AUSCAN and FIHOA questionnaires. Patients with EOA experienced more pain and similar levels of functional impairment compared to patients with ‘low disease activity’ inflammatory arthritis after correction for number of erosive and active inflammatory joints. The clinical burden of EOA is shown to be higher than non-erosive OA. While the number of radiographic affected joints seems to be the strongest predictor for functional impairment in patients with EOA, the number of tender joints is the strongest predictor towards pain. The pain experienced by patients with EOA is insufficiently covered by the present analgesics and new treatment modalities are warranted to prevent structural damage. In the second part of this thesis, the Dutch version of the FIHOA was developed and validated in a small cohort of patients with symptomatic and asymptomatic HOA. It was found to be valid for use in HOA and construct validity was demonstrated with the AUSCAN as referent. A different approach towards function between both questionnaires was suggested: while AUSCAN is more sensitive to the presence of pain, FIHOA is more influenced by the presence of underlying structural damage. However, no superiority of one of both questionnaires was proven. Additionally, a new outcome measure to quantify radiographic progression in EOA was developed and validated. The Ghent University Scoring System, GUSS™, is a new quantitative scoring system based on scoring pathology in subchondral bone, subchondral plate and joint space narrowing. The scoring system is developed for monitoring radiographic progression and should not be used for diagnostic purposes. A decrease in total score reflects erosive progression, while an increase represents radiographic reparative phenomena. The scoring system was proven to be reliable and sensitive to change. A minimal change of at least 40 units over 12 months has to be present to detect ‘real’ change over measurement error. However, this can still be reduced by training. The third part of this thesis reports the results of a placebo-controlled randomized clinical trial in which the efficacy of adalimumab, a monoclonal anti-TNF-α antibody in EOA was assessed. Sixty patients were allocated to treatment with adalimumab or placebo during 12 months. Adalimumab, 40 mg, or placebo was administered subcutaneously, every two weeks. The primary endpoint of this study was the radiographic erosive progression. Secondary endpoints were clinical outcomes, such as number of tender and swollen joints, and functional impairment (by AUSCAN). Adalimumab is proven to be efficacious in reducing the number of new erosive joints in a subgroup of patients presenting with palpable joint effusion at baseline. Significantly less erosive evolution is seen in these joints in the adalimumab treated group compared to placebo. Clinical data do not show improvement in the adalimumab treated group compared to placebo. Safety data are reassuring and do not show significant differences between both groups. The results need confirmation in larger clinical trials and the significance of the palpable joint effusion as prognostic factor for response to TNF-α blockers should be further investigated. In the fourth part of this thesis, the sonographic soft tissue and structural changes were explored in EOA and compared with non-erosive OA patients. A descriptive sonographic and a comparative study between US, MRI, radiography, and clinical examination were performed. US is able to detect erosions in the radiographic phases preceding the erosive phase. Sensitivity of US is higher in detecting erosions compared to radiography without loss of specificity. Sonographic soft tissue changes are commonly seen in EOA and in non-erosive OA. These can not be interpreted to be disease-specific for EOA. In EOA, soft tissue changes did occur twice as frequent in ‘E’ joints compared to the other pre-erosive radiographic phases. However, the contribution of these ‘inflammatory’ or soft tissue changes in the erosive process of OA needs to be further elucidated.. US is proven to be a valid imaging tool in EOA: high agreement with MRI was found in detecting synovitis, joint effusion, and erosions. This implies that ‘true’ erosions, and soft tissue changes are detected by US in EOA and non-erosive OA. In conclusion, this thesis provides a valuable contribution to the current knowledge on EOA and other subtypes of HOA. It provides new insights on the clinical presentation and highlights the clinical burden of EOA, warranting more aggressive treatment. The results described in this thesis contribute to our understanding of the anatomic basis of EOA. The effect of monoclonal anti-TNF-α antibodies on the radiographic progression of EOA adds to the knowledge on the cytokines involved in the disease. We have addressed several aspects of this subtype of HOA and conclude that this complex disease and the patients suffering from it merit more attention to further unravel the pathogenesis and etiology and investigate the potential of new treatment modalities.
Please use this url to cite or link to this publication:
author
promoter
UGent and UGent
organization
year
type
dissertation (monograph)
subject
keyword
erosive osteoarthritis, adalimumab, magnetic resonance imaging, interphalangeal joints, ultrasound
pages
195 pages
publisher
Ghent University. Faculty of Medicine and Health Sciences
place of publication
Ghent, Belgium
defense location
Gent : UZ (auditorium C)
defense date
2010-11-29 17:30
ISBN
9789490695439
language
English
UGent publication?
yes
classification
D1
additional info
dissertation consists of copyrighted materials
copyright statement
I have transferred the copyright for this publication to the publisher
id
1181178
handle
http://hdl.handle.net/1854/LU-1181178
date created
2011-03-02 20:40:42
date last changed
2011-03-29 14:38:56
@phdthesis{1181178,
  abstract     = {Osteoarthritis of the hand (HOA) is a common musculoskeletal disorder characterized by degradation of cartilage and changes in subchondral bone. The disease has a heterogeneous character and several subsets have been proposed. One of the subsets is affecting the interphalangeal (IP) finger joints: 2 subtypes are recognized, the erosive and non-erosive type. The diagnosis of erosive osteoarthritis of the IP finger joints (EOA) is based on the presence of radiographic subchondral erosions which lead to deformities and sometimes bony ankylosis of the joint. The higher clinical burden and worse outcome than non-erosive IP finger joint OA is apparent from daily clinical practice. Although the radiographic features of EOA are well characterized, the etiopathogenesis of the disease and etiology responsible to drive the {\textquoteleft}inflammatory clinical picture{\textquoteright} of EOA are less well understood.  The aim of this work described in this thesis is to contribute to the knowledge on EOA in several aspects, in order to improve the approach to patients with several subtypes of HOA. In addition, we aimed to situate the level of pain and functional impairment in EOA in relation to other rheumatic disorders. With the use of imaging tools, we tried to identify differences in anatomic basis between EOA and non-erosive OA. Ultimately, the better knowledge and recognition of the disease and its subtypes may contribute to adequate treatment. 
The first part of this thesis studied the differences in functional impairment and pain between several groups of HOA, depending on the presence of erosive disease, and patients with inflammatory arthritis of the finger joints. Functional impairment was measured by the AUSCAN and FIHOA questionnaires. Patients with EOA experienced more pain and similar levels of functional impairment compared to patients with {\textquoteleft}low disease activity{\textquoteright} inflammatory arthritis after correction for number of erosive and active inflammatory joints. The clinical burden of EOA is shown to be higher than non-erosive OA. While the number of radiographic affected joints seems to be the strongest predictor for functional impairment in patients with EOA, the number of tender joints is the strongest predictor towards pain. The pain experienced by patients with EOA is insufficiently covered by the present analgesics and new treatment modalities are warranted to prevent structural damage.
In the second part of this thesis, the Dutch version of the FIHOA was developed and validated in a small cohort of patients with symptomatic and asymptomatic HOA. It was found to be valid for use in HOA and construct validity was demonstrated with the AUSCAN as referent. A different approach towards function between both questionnaires was suggested: while AUSCAN is more sensitive to the presence of pain, FIHOA is more influenced by the presence of underlying structural damage. However, no superiority of one of both questionnaires was proven. 
Additionally, a new outcome measure to quantify radiographic progression in EOA was developed and validated. The Ghent University Scoring System, GUSS{\texttrademark}, is a new quantitative scoring system based on scoring pathology in subchondral bone, subchondral plate and joint space narrowing. The scoring system is developed for monitoring radiographic progression and should not be used for diagnostic purposes. A decrease in total score reflects erosive progression, while an increase represents radiographic reparative phenomena. The scoring system was proven to be reliable and sensitive to change. A minimal change of at least 40 units over 12 months has to be present to detect {\textquoteleft}real{\textquoteright} change over measurement error. However, this can still be reduced by training.
The third part of this thesis reports the results of a placebo-controlled randomized clinical trial in which the efficacy of adalimumab, a monoclonal anti-TNF-\ensuremath{\alpha} antibody in EOA was assessed. Sixty patients were allocated to treatment with adalimumab or placebo during 12 months. Adalimumab, 40 mg, or placebo was administered subcutaneously, every two weeks. The primary endpoint of this study was the radiographic erosive progression. Secondary endpoints were clinical outcomes, such as number of tender and swollen joints, and functional impairment (by AUSCAN). Adalimumab is proven to be efficacious in reducing the number of new erosive joints in a subgroup of patients presenting with palpable joint effusion at baseline. Significantly less erosive evolution is seen in these joints in the adalimumab treated group compared to placebo. Clinical data do not show improvement in the adalimumab treated group compared to placebo. Safety data are reassuring and do not show significant differences between both groups. The results need confirmation in larger clinical trials and the significance of the palpable joint effusion as prognostic factor for response to TNF-\ensuremath{\alpha} blockers should be further investigated.
In the fourth part of this thesis, the sonographic soft tissue and structural changes were explored in EOA and compared with non-erosive OA patients.  A descriptive sonographic and a comparative study between US, MRI, radiography, and clinical examination were performed. US is able to detect erosions in the radiographic phases preceding the erosive phase. Sensitivity of US is higher in detecting erosions compared to radiography without loss of specificity. Sonographic soft tissue changes are commonly seen in EOA and in non-erosive OA. These can not be interpreted to be disease-specific for EOA. In EOA, soft tissue changes did occur twice as frequent in {\textquoteleft}E{\textquoteright} joints compared to the other pre-erosive radiographic phases. However, the contribution of these {\textquoteleft}inflammatory{\textquoteright} or soft tissue changes in the erosive process of OA needs to be further elucidated.. US is proven to be a valid imaging tool in EOA: high agreement with MRI was found in detecting synovitis, joint effusion, and erosions. This implies that {\textquoteleft}true{\textquoteright} erosions, and soft tissue changes are detected by US in EOA and non-erosive OA.
In conclusion, this thesis provides a valuable contribution to the current knowledge on EOA and other subtypes of HOA. It provides new insights on the clinical presentation and highlights the clinical burden of EOA, warranting more aggressive treatment. The results described in this thesis contribute to our understanding of the anatomic basis of EOA. The effect of monoclonal anti-TNF-\ensuremath{\alpha} antibodies on the radiographic progression of EOA adds to the knowledge on the cytokines involved in the disease. We have addressed several aspects of this subtype of HOA and conclude that this complex disease and the patients suffering from it merit more attention to further unravel the pathogenesis and etiology and investigate the potential of new treatment modalities.},
  author       = {WITTOEK, RUTH},
  isbn         = {9789490695439},
  keyword      = {erosive osteoarthritis,adalimumab,magnetic resonance imaging,interphalangeal joints,ultrasound},
  language     = {eng},
  pages        = {195},
  publisher    = {Ghent University. Faculty of Medicine and Health Sciences},
  school       = {Ghent University},
  title        = {Beyond the scope of erosive osteoarthritis of the interphalangeal finger joints: new insights from epidemiological, clinical and imaging based studies},
  year         = {2010},
}

Chicago
WITTOEK, RUTH. 2010. “Beyond the Scope of Erosive Osteoarthritis of the Interphalangeal Finger Joints: New Insights from Epidemiological, Clinical and Imaging Based Studies”. Ghent, Belgium: Ghent University. Faculty of Medicine and Health Sciences.
APA
WITTOEK, R. (2010). Beyond the scope of erosive osteoarthritis of the interphalangeal finger joints: new insights from epidemiological, clinical and imaging based studies. Ghent University. Faculty of Medicine and Health Sciences, Ghent, Belgium.
Vancouver
1.
WITTOEK R. Beyond the scope of erosive osteoarthritis of the interphalangeal finger joints: new insights from epidemiological, clinical and imaging based studies. [Ghent, Belgium]: Ghent University. Faculty of Medicine and Health Sciences; 2010.
MLA
WITTOEK, RUTH. “Beyond the Scope of Erosive Osteoarthritis of the Interphalangeal Finger Joints: New Insights from Epidemiological, Clinical and Imaging Based Studies.” 2010 : n. pag. Print.