Interleukin-1 receptor antagonist treatment of rheumatoid arthritis patients: Radiologic progression and correlation of Genant/Sharp and Larsen scoring methods

doi:10.1053/sarh.2001.23697

Seminars in Arthritis and Rheumatism

Volume 30, Issue 5, Supplement, April 2001, Pages 26-32

https://doi.org/10.1053/sarh.2001.23697 Get rights and content

Abstract

Objective: The Genant/Sharp scoring method is a validated radiologic scoring system useful for diagnosing, classifying, and defining specific clinical problems associated with rheumatoid arthritis (RA). The Genant/Sharp scoring method is described, and its level of correlation with the Larsen scoring method is discussed. Method: The Genant/Sharp scoring system evaluates erosion, joint space narrowing (JSN), and a combination of erosion and JSN referred to as the total score. This method was used to determine change in radiographic progression during 2 consecutive 6-month intervals within a multicenter, double-blind, placebo-controlled study of recombinant human interleukin-1 receptor antagonist (IL-1ra) in patients with RA. These results were compared with the results obtained through the Larsen scoring method to determine their correlation. Results: The Genant/Sharp scoring method showed a moderate correlation with the Larsen scoring method, particularly at baseline, and showed similar treatment trends in a study of IL-1ra in patients with RA. Conclusion: The Genant/Sharp scoring method provides an alternative to the Sharp and Larsen approaches for radiographic assessment in RA. Semin Arthritis Rheum 30:26-32 (Suppl 2). Copyright © 2001 by W.B. Saunders Company

Section snippets

Method

With the Genant-Sharp scoring approach, one can use a single observer, as was the case in this trial, or multiple observers 4, 5. There is a broad reading scale, typically 8 or 9 steps, and the examinations are viewed side by side—that is, simultaneously—and blinded to sequence. This last consideration is an important difference between Genant/Sharp and Larsen scoring. Viewing the images side by side makes it possible to assess subtle progression and/or regression. This technique requires

Genant/Sharp score results

In the present trial, radiographs were obtained at baseline, 6 months, and 12 months. Figure 2 illustrates the mean changes in total score during the 2 consecutive 6-month intervals.

. Genant/Sharp total score: change in radiographic progression during 2 consecutive 6-month intervals. During the first 6 months, mean total scores of patients in the placebo group increased approximately twice as much as scores of patients in the active treatment groups. Adjusted means for the 6- to 12-month data

Correlation of Genant/Sharp and Larsen scores

The results of the Larsen score indicate that suppression of disease progression did not reach statistical significance, in part because of the greater scatter with this scoring mechanism. Figure 5 shows the correlation of the total score by the Genant/Sharp approach and the Larsen score at baseline.

. Total scores: Genant/Sharp and Larsen at baseline (BL). Genant/Sharp scores are plotted on the y-axis and Larsen scores on the x-axis. Correlation of total Genant/Sharp and Larsen scores at

Discussion

The randomized, double-blind, placebo-controlled, dose-ranging, multicenter study described in this article has shown that IL-1ra slowed the progression of disease in patients with RA. By using radiologic evidence reflected by the different scoring methods (ie, Larsen and Genant/Sharp), the objective—quantifiable impact of this novel therapy—can be readily assessed. In fact, we believe that the Genant/Sharp method shows greater sensitivity in detecting the study endpoint, drug efficacy, than

Conclusion

The Genant/Sharp scoring method, developed using 15 years of clinical experience, showed a significant reduction in progression of erosion and JSN in subjects treated with IL-1ra for 6 months. Of special significance, the reduction in progression of JSN was sustained in the second 6 months ⁽⁵⁾. The Genant/Sharp and Larsen scoring methods show a moderate correlation, particularly at baseline. Although they do not correlate strongly with regard to change, they do show similar treatment trends.

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Methods of assessing radiographic change in rheumatoid arthritis
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JT Sharp et al.
Methods of scoring the progression of radiologic changes in rheumatoid arthritis: correlation of radiologic, clinical and laboratory abnormalities
Arthritis Rheum
(1971)
A Larsen et al.
Hand radiography of 200 patients with rheumatoid arthritis repeated after an interval of one year
Scand J Rheumatol
(1987)

There are more references available in the full text version of this article.

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Structural lesion assessments of rheumatoid arthritis: Radiography, ultrasound and MRI
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L’évaluation des dégâts structuraux au cours de la polyarthrite rhumatoïde fait partie intégrante de la prise en charge des patients. Initialement, celle-ci se réalisait uniquement par des radiographies. Le score de Sharp modifié par van der Heijge est le système de quantification des dégâts articulaires non réalisé en pratique courante mais uniquement lors de protocoles de recherche. Ce score est divisé en deux sous-scores, l’un évaluant les érosions et l’autre le pincement articulaire. Il n’évalue au final que l’atteinte des mains-poignets et des avant-pieds. Par ailleurs, les dégâts articulaires sont le reflet d’une maladie mal équilibré auparavant. L’échographie articulaire est de plus en plus utilisée car est un examen non irradiant permettant une évaluation des érosions avec une meilleure susceptibilité mais surtout une évaluation de l’inflammation articulaire. L’échographie articulaire peut évaluer facilement l’ensemble des articulations. De nombreux scores ont été développés afin d’évaluer l’activité de la PR, mais ceux-ci peuvent être chronophages et restent peu réalisés dans la pratique courante. L’IRM est également non irradiante mais peu pratiquée car moins accessible avec une durée d’acquisition longue pour un faible nombre d’articulations analysées. Le score de RAMRIS évalue les érosions, l’œdème osseux et la synovite du poignet et des métacarpophalangiennes.
Joint structural damage evaluation during rheumatoid arthritis is part of patient's management. Initially, this was performed only by X-rays. The Sharp-van der Heijde modified score is actually the gold standard to quantify joint damage during research protocols, but not in daily practice. This score is divided into two sub-scores, one evaluating erosions and the other one the space narrowing. It only evaluates hand-wrist and forefoot involvement. In addition, joint damage is related to disease activity before its realization. Joint ultrasound used is increasingly due to non-irradiant character allowing evaluation of erosions with high susceptibility but also evaluation of the joint inflammation. Joint ultrasound can easily evaluate all joints. However, many scores have been developed to evaluate RA activity. However, they are time consuming and so not performed in daily practice. MRI is also non-irradiant method. However, it is rarely performed due to its low accessibility with a long acquisition time for a small number of articulations analyzed. The RAMRIS score evaluates erosions, bone edema, and wrist synovitis and metacarpophalangeal joints.
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Targeting cytokines as a treatment option in human disease has been extensively explored during the last decades, and a growing number of cytokine-targeted therapy options have become available. Since interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine it is not surprising that treatment strategies targeting IL-1 were some of the first to be explored. IL-1 blockers have been proven to be beneficial in a wide variety of human diseases that are associated with inflammation. Blocking IL-1 can be established at the level of inhibiting IL-1 receptor signaling or by binding IL-1 making it unavailable for signaling. The advantage of such a treatment strategy is that the drug does not have to enter the cell or have to be metabolized in order to elicit its effects. This chapter describes the bioactivity of IL-1, how it is controlled and induces signaling, and provides an overview of the effects of blocking IL-1 in human disease.
Imaging of Rheumatoid Arthritis
2013, Rheumatic Disease Clinics of North America
Citation Excerpt :
Most systems focus on the hands and feet because damage in the hands and feet is highly correlated with overall joint damage.5 The most widely used scoring systems are the Sharp/van der Heijde (SvdH) method, the Larsen method, and the Sharp/Genant method.6,7 The SvdH method assesses erosions and joint space narrowing separately, and it can be used for both hand and foot films.8
Abatacept for the treatment of rheumatoid arthritis: A review
2007, Current Therapeutic Research - Clinical and Experimental
Abstract
Background: Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies—rituximab and abatacept—are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs.
Objectives: The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium.
Methods: The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000–September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations.
Results:The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%–4.2%) of discontinuation due to adverse events.
Conclusion: The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.
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Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the joints which leads to the destruction of cartilage and bone. Plain film radiography is the standard method for evaluating disease progression and for establishing the efficacy of new disease modifying antirheumatic drugs (DMARD). Because of the importance of radiographic progression in determining long term outcomes, a standarized, systematic method to evaluate and quantify the amount and progression of radiographic damage caused by RA is desirable. An exhaustive review of the plain radiology in RA is presented and include: the different radiographic scoring methods and their disadvantages, the methods of reading films and the guidelines for presentation of results, the main clinical trials that evaluate disease progression and the efficacy of the different agents in the treatment of RA and the hypothesis that repair of structural damage can occurs.
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^☆: Harry K. Genant, MD: Professor of Radiology, Medicine, Epidemiology, and Orthopedic Surgery, University of California School of Medicine, San Francisco, CA.

^☆☆: Address reprint requests to Harry K. Genant, MD, Box 1250, Radiology Department, University of California School of Medicine, San Francisco, CA 94143.

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Interleukin-1 receptor antagonist treatment of rheumatoid arthritis patients: Radiologic progression and correlation of Genant/Sharp and Larsen scoring methods☆,☆☆

Abstract

Section snippets

Method

Genant/Sharp score results

Correlation of Genant/Sharp and Larsen scores

Discussion

Conclusion

Am J Med

Methods of scoring the progression of radiologic changes in rheumatoid arthritis: correlation of radiologic, clinical and laboratory abnormalities

Arthritis Rheum

Hand radiography of 200 patients with rheumatoid arthritis repeated after an interval of one year

Scand J Rheumatol