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Anti-TNF agents may slow, protect against RA-related joint destruction, disability, work loss

Saturday, June 16 2007 | Comments
Evidence Grade 0 What's This?
Rheumatoid arthritis can lead to joint destruction, disability, and job loss, but anti-tumor necrosis factor therapies have shown their ability to slow or even prevent these outcomes, according to 2 rheumatology experts.

Dr. Josef Smolen, chairman of the rheumatology department at Vienna General Hospital, began by explaining the "triad" of rheumatology and how the components of relentlessly active disease, progressive joint destruction, and permanent disability are linked to each other.

He said that disease activity leads to joint damage and is associated with the activity component of disability. Joint damage is also associated with damage-related disability, but not with activity-related disability.

In turn, disability, or functional impairment, is the result of disease activity and joint damage. Functional impairment governs RA throughout its course, and irreversible disability is a consequence of joint damage.

However, data from the PREMIER and ATTRACT trials have shown that TNF blockade therapy combined with methotrexate disassociates the response of signs and symptoms from the response of joint damage. For example, patients who continued to have higher disease activity showed smaller average changes in total Sharp score from baseline if they received methotrexate combined with adalimumab or infliximab than if they received methotrexate monotherapy.

Dr. Smolen said this phenomenon can be explained by the threshold hypothesis, which states that patients start to show pain and swelling when they reach a first threshold, but that joint destruction does not occur until they reach a second threshold. It is hoped that once a TNF inhibitor is given, both the inflammation and destruction will be reduced as time passes, but this does not happen in all patients. Different patients fall into different levels among the thresholds with TNF therapy.

"Given that healing is not something that we can achieve today, and given that joint destruction leads to irreversible disability, our aim, therefore, today, must be to prevent joint destruction ..., " Dr. Smolen said.

"[P]rotection from disability and restoration of normal function is an important goal in the treatment of RA. ... TNF inhibitors plus methotrexate interfere with osteoclast activation and thus highly retard or prevent progression of joint damage. And the combination of methotrexate and anti-TNF [therapy] not only inhibits inflammation but is currently the most effective therapy to control joint destruction," he added.

Dr. Paul Emery, head of the musculoskeletal medicine academic unit at the University of Leeds in the United Kingdom, took the issue of RA disability a step further into real life, such as quality-of-life and work outcomes.  

Several studies have shown that job loss is prevalent in patients with RA, resulting in significant economic consequences.  

But results from the ASPIRE trial and research conducted by Yelin et al have shown the positive effect infliximab and etanercept can have on employment-related outcomes.

Dr. Emery highlighted recent findings from DE032, a companion trial to PREMIER, in which 664 PREMIER participants provided work productivity, health care resource utilization and clinical outcomes information.

In both the employed and homemaker groups, absenteeism due to RA was significantly lower at years 1 and 2 for patients who received adalimumab plus methotrexate relative to those who received methotrexate alone (P<.001 for all). Also, presenteeism, or the degree of work performance, showed greater improvements from baseline through 104 weeks for the employed and homemaker groups that received combination treatment rather than monotherapy (P<.05 at certain time points).

He went on to present new data from the PROWD trial, the first study to use work as a primary endpoint.

Specifically, the primary outcome measure was job loss from any cause at or after week 16 or imminent job loss, defined as a failure to achieve a 20% response based on American College of Rheumatology criteria at or after week 16 and a severe/deteriorating score on the RA Work Instability Scale. At baseline, most of the 148 participants had a medium or high work disability risk.

Dr. Emery pointed out that many patients in the methotrexate monotherapy arm dropped out of the study before the 16-week time point, making results of the primary endpoint nonsignificant. Combining adalimumab and methotrexate prevented approximately half of the patients from losing their jobs, whereas patients who received methotrexate monotherapy were actually losing their jobs before 16 weeks. Significantly fewer patients who received the drug combination rather than methotrexate monotherapy had working time lost (P=.038) or loss of productivity (P=.021). Functional improvement (as measured by the change in Health Assessment Questionnaire score from baseline) was also significantly better with adalimumab plus methotrexate at weeks 16 and 56 (P<.05 at both time points).

"Thus, the conclusion is that you can have the ability to ... reduce job loss and work time loss by using adalimumab in early [RA] disease. ... You already know it works; this gives us the opportunity to show that it is actually cost effective in these patients ...," he said.

By Shayna Muckerheide

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