Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switzerland
1 Department of Physical Medicine and Rehabilitation, University Hospital Munich, Germany and
2 Department of Rheumatology, University Medical Centre Nijmegen, The Netherlands
Rheumatoid arthritis (RA) is mainly characterized by symmetrical erosive synovitis and occasional multisystem involvement. Most patients exhibit a chronic fluctuating course of disease that, if left untreated, results in progressive joint destruction, deformity, disability and premature death. It frequently affects patients in their most productive years, and thus disability results in a major economic loss [1].
There is general agreement that rheumatoid inflammation should be controlled as soon and as completely as possible, and that control should be maintained for as long as possible, consistent with patient safety [2]. It is recommended [3] that, in nearly all cases, patients should be treated with a disease-modifying anti-rheumatic drug (DMARD) or a biological agent. DMARDs should be used in doses high enough to reduce inflammation, unless a full treatment effect is gained at a lower dose or limiting toxicity is reached. Treatment failure can then be defined simply as occurring when rheumatoid inflammation is not controlled [3]. When adequate control is not achieved, the DMARD should be changed, or another DMARD or biological agent added [3].
Unfortunately, most patients achieve only partial suppression of rheumatoid inflammation and many lose therapeutic benefit after an initial good response. Additive combination therapy may also produce only temporary benefit [2]. In general, we cannot predict with enough certainty the disease course and the occurrence of response and toxicity for individual RA patients. While enriched by new treatment options, the management of RA continues to be a challenge [2, 4].
Accepting that the goal of treatment is to reach optimal control of rheumatoid inflammation or even remission, it is clear that the management of RA should include systematic and regular evaluation of rheumatoid inflammation. Treatment efficacy should be monitored with the same seriousness as the monitoring of toxicity [57]. The treatment programme can be adapted if necessary, from the perspectives of both benefit and harm [1]. Such a trade-off could be a good moment to include patient preferences and to educate the patient about treatment options. In daily clinical practice, regular and systematic monitoring of inflammatory activity is useful to:
An example of monitoring for the titration of inflammatory activity is depicted in Figure 1. The usefulness and feasibility of dose titration in RA patients treated with anti-tumour necrosis factor
(anti-TNF-
) is shown in a study by den Broeder et al. [8] in this issue of Rheumatology, demonstrating the advantages of tailoring anti-TNF-
treatment over the one size fits all dosing scheme.
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In daily clinical practice, there are several barriers to regular monitoring that may not be different from the barriers against the use of outcome measures. Examples are: the apprehension of non-laboratory data as soft; unfamiliarity with scores and difficulty with their interpretation; uncertainty about the impact on clinical care or health; the necessary resources of time and personnel; and fear of annoying patients with measurements [1518]. It is important to recognize these barriers, and they need to be overcome.
However, by far the most important barrier for the clinician is the problem of knowing when rheumatoid inflammation is optimally controlled or in remission. Which measures should be used? What are the criteria for judging whether inflammatory activity is under control? There is general agreement regarding the measures and examinations that are most appropriate for evaluating change in randomized controlled trials (RCTs) evaluating DMARDs [1922]. In daily clinical practice, however, the aim is to determine and evaluate actual status rather than change in status [19, 23]. There are no defined gold standards of severity for the measures used to assess RA. Thus, it is not clear how low you have to go in which measures in order to be confident that there is remission or that inflammatory activity is under control. However, the measures that clinicians might apply in daily clinical practice preferably include the American College of Rheumatology (ACR) core set measures, for practical and methodological reasons, even if these measures approximate rather than measure the underlying synovitis.
The two approaches most established to measure change in RCTs are the ACR improvement criteria and the European League Against Rheumatism (EULAR) response criteria [12, 22].
The ACR improvement criteria (e.g. ACR20) identify a patient as a responder if there is improvement (e.g. >20%) in both tender and swollen joint counts and in three of the following five measures: pain, patient's global assessment, physician's global assessment, disability, and an acute-phase reactant [21]. The ACR improvement criteria are designed to discriminate placebo from drug in RCTs; they are not helpful in assessing actual status in clinic patients [19]. The main disadvantage of such a response measure is that the amount of inflammatory activity you end up with is unknown. To give further insight into status and prognosis, percentile methods for core set measures have been developed, with which the severity status of an individual patient can be compared with that of a reference group [19]. However, it is a disadvantage when changes in multiple measures must be interpreted at the same time, and it is still difficult to interpret their meaning.
The EULAR response criteria classify the patient as a good, moderate or non-responder, depending on both the magnitude of improvement and the absolute level of the Disease Activity Score (DAS28) reached [22]. The DAS28 is an index that includes the results of swollen joint count, tender joint count, erythrocyte sedimentation rate (ESR) and a general health question. The DAS28 ranges virtually from 0 to 10 and a score below 3.2 is defined as low disease activity. A low level of DAS28 over time reduces the probability of progression of radiological visible joint damage [24, 25]. Thus, the DAS28 is a suitable aid in determining and evaluating actual status and change in status, particularly when applied to individual patients with RA. As an example, the DAS28 was used to individually increase the dose of methotrexate, starting with 7.5 mg/week, in a trial on the effects of the addition of folates [26]. How the DAS28 can be used in a step-down regimen is demonstrated by the study of den Broeder et al. in this issue [8].
Clinical variables, as in the DAS28, are just approximate indicators of the underlying synovitis. Clinical assessments may be complemented by information from patient questionnaires such as the Rheumatoid Arthritis Disease Activity Index (RADAI) [27]. However, it is not advisable to base treatment decisions solely on questionnaire results [28]. To be surer about the long-term course of RA in an individual patient, monitoring can include disability and joint damage.
It is important to monitor inflammatory activity on a regular basis, perhaps every visit, every 3 months, or with every change in DMARD and dose. In any case, inflammatory activity must be documented not only if the patient presents with clearly active inflammation, but also when improvement occurs or treatment effects are expected. Long-term effects (disability and joint damage) may be monitored every 6 months or annually.
It would greatly facilitate clinical decision-making if the information needed to judge inflammatory activity were at hand shortly after the assessment. Then, relevant decisions could be made in the presence of the patient.
In primary care, several RCTs have been performed on the effectiveness of computerized decision-support systems (CDSS), including measurement feedback and guidelines, mainly in patients with hypertension, diabetes or the need for anticoagulation, but also in patients with arthritis [2937]. According to these studies, CDSS were generally ineffective in changing physician performance or health outcomes. It is important to realize that monitoring RA is not an intervention that causes health effects, but medication may do so. Physician performance is the important link between monitoring and health effects through medication.
The goal of treatment of RA is to control rheumatoid inflammation as soon and as completely as possible, and this control should be maintained for as long as possible. In order to decide if treatment goals have been reached and to support adaptations of the treatment programme, the management of RA patients in daily clinical practice should include systematic and regular evaluation of rheumatoid inflammation. To determine the status and change of individual RA patients in daily clinical practice, core set measures and response criteria may be used with some care.
Acknowledgments
We wish to thank Leanne Pobjoy for her assistance in the preparation of the manuscript.
Notes
Correspondence to: J. Fransen, Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Gloriastrasse 25, CH-8091 Zurich, Switzerland.
References