The merits of monitoring: should we follow all our rheumatoid arthritis patients in daily practice?

J. Fransen, G. Stucki1 and P. van Riel2

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 1Go. The usefulness and feasibility of dose titration in RA patients treated with anti-tumour necrosis factor {alpha} (anti-TNF-{alpha}) is shown in a study by den Broeder et al. [8] in this issue of Rheumatology, demonstrating the advantages of tailoring anti-TNF-{alpha} treatment over the ‘one size fits all’ dosing scheme.



View larger version (16K):
[in this window]
[in a new window]
 
FIG. 1.  An example of the monitoring of disease activity (DAS, RADAI), disability (HAQ) and joint damage (X-ray) over time (months.yr) in an individual RA patient.

 
Initiatives to establish computerized decision-support systems for the monitoring of RA have emerged in Switzerland and Sweden [4, 9, 10]. Generally, monitoring and documentation are not used regularly in daily clinical practice [1113]. The statement by Pincus [14] may be recognized: ‘Many, if not most, clinicians feel it is not necessary to document obvious clinical improvement recognised by both the patient and the clinician. A positive response to the question "How are you doing?" is sufficient’ [14].

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. Back

References

  1. Guidelines for the management of rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum1996;39:713–22.[Medline]
  2. Moreland LW, Russell AS, Paulus HE. Management of rheumatoid arthritis: the historical context. J Rheumatol2001;28:1431–52.[ISI][Medline]
  3. Wolfe F, Cush JJ, O'Dell JR et al. Consensus recommendations for the assessment and treatment of rheumatoid arthritis. J Rheumatol2001;28:1413–30.[ISI][Medline]
  4. Stucki G, Sangha O. Clinical quality management: putting the pieces together. Arthritis Care Res1996;9:405–12.[Medline]
  5. Wijnands MJ, Van Riel PL. Management of adverse effects of disease-modifying antirheumatic drugs. Drug Safety1995;13:219–27.[ISI][Medline]
  6. Simon CH, Vliet-Vlieland TP, Dijkmans BA et al. Laboratory screening for side effects of disease modifying antirheumatic drugs in daily rheumatological practice. Scand J Rheumatol1998;27:170–9.[ISI][Medline]
  7. Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Arthritis Rheum1996;39:723–31.[Medline]
  8. den Broeder AA, Creemers MCW, Van Gestel AM, Van Riel PLCM. Dose titration using the Disease Activity Score (DAS28) in rheumatoid arthritis patients treated with anti-TNF-{alpha}. Rheumatology2002;41:518–22.[Abstract/Free Full Text]
  9. Uitz E, Fransen J, Langenegger T, Stucki G. Clinical quality management in rheumatoid arthritis: putting theory into practice. Swiss Clinical Quality Management in Rheumatoid Arthritis. Rheumatology2000;39:542–9.[Abstract/Free Full Text]
  10. Geborek P, Saxne T. Clinical protocol for monitoring of targeted therapies in rheumatoid arthritis. Rheumatology2000;39:1159–61.[Free Full Text]
  11. Wolfe F, Pincus T. Listening to the patient: a practical guide to self-report questionnaires in clinical care. Arthritis Rheum1999;42:1797–808.[ISI][Medline]
  12. Bellamy N, Kaloni S, Pope J, Coulter K, Campbell J. Quantitative rheumatology: a survey of outcome measurement procedures in routine rheumatology outpatient practice in Canada. J Rheumatol1998;25:852–8.[ISI][Medline]
  13. Bellamy N, Muirden KD, Brooks PM, Barraclough D, Tellus MM, Campbell J. A survey of outcome measurement procedures in routine rheumatology outpatient practice in Australia. J Rheumatol1999;26:1593–9.[ISI][Medline]
  14. Pincus T. Documenting quality management in rheumatic disease: are patient questionnaires the best (and only) method? Arthritis Care Res1996;9:339–48.[Medline]
  15. Deyo RA, Patrick DL. Barriers to the use of health status measures in clinical investigation, patient care, and policy research. Med Care1989;27(3 Suppl.):S254–68.[ISI][Medline]
  16. Deyo RA, Carter WB. Strategies for improving and expanding the application of health status measures in clinical settings. A researcher–developer viewpoint. Med Care1992;30(5 Suppl.):S176–86.
  17. Golden WE. Health status measurement. Implementation strategies. Med Care1992;30(5 Suppl.):S187–95.
  18. Patrick DL. Strategies for improving and expanding the application of health status measures in clinical settings. Discussion. Med Care1992;30(Suppl.):S198.
  19. Wolfe FW, O'Dell JR, Kavanaugh A, Wilske K, Pincus T. Evaluating severity and status in rheumatoid arthritis. J Rheumatol2001;28:1453–62.[ISI][Medline]
  20. Boers M, Tugwell P, Felson DT et al. World Health Organization and International League of Associations for Rheumatology core endpoints for symptom modifying antirheumatic drugs in rheumatoid arthritis clinical trials. J Rheumatol1994;(Suppl.)41:86–9.
  21. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum1995;38:727–35.[ISI][Medline]
  22. Van Gestel AM, Prevoo ML, Van't Hof MA, Van Rijswijk MH, Van de Putte LB, Van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum1996;39:34–40.[Medline]
  23. Van Riel PL, Schumacher HR. How does one assess early rheumatoid arthritis in daily clinical practice? Best Pract Res Clin Rheumatol2001;15:67–76.
  24. Welsing PMJ, Swinkels HL, Van Gestel AM, Van Riel PLCM. The relation between disease activity and radiologic progression of joint damage in rheumatoid arthritis. Arthritis Rheum2001;44(9 Suppl.):Abstract 1349.
  25. Landewe RBM, Boers M, Verhoeven AC, Boonen A, Van der Heijde DMFM, Van der Linden S. A longitudinal analysis of the relationship between change in DAS28 and change in radiological progression. Arthritis Rheum2001;44(9 Suppl.):Abstract 737.
  26. Van Ede AE, Laan RF, Rood MJ et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum2001;44:1515–24.[ISI][Medline]
  27. Stucki G, Liang MH, Stucki S, Bruhlmann P, Michel BA. A self-administered rheumatoid arthritis disease activity index (RADAI) for epidemiologic research. Psychometric properties and correlation with parameters of disease activity. Arthritis Rheum1995;38:795–8.[ISI][Medline]
  28. Fransen J, Langenegger T, Michel BA, Stucki G. Feasibility and validity of the RADAI, a self-administered rheumatoid arthritis disease activity index. Rheumatology2000;39:321–7.[Abstract/Free Full Text]
  29. Goldberg HI, Wagner EH, Fihn SD et al. A randomized controlled trial of CQI teams and academic detailing: can they alter compliance with guidelines? Jt Comm J Qual Improv1998;24:130–42.[Medline]
  30. Montgomery AA, Fahey T. A systematic review of the use of computers in the management of hypertension. J Epidemiol Community Health1998;52:520–5.[Abstract]
  31. Montgomery AA, Fahey T, Peters TJ, MacIntosh C, Sharp DJ. Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial. BMJ2000;320:686–90.[Abstract/Free Full Text]
  32. Hetlevik I, Holmen J, Kruger O. Implementing clinical guidelines in the treatment of hypertension in general practice. Evaluation of patient outcome related to implementation of a computer-based clinical decision support system. Scand J Primary Health Care1999;17:35–40.[ISI][Medline]
  33. Hetlevik I, Holmen J, Kruger O, Kristensen P, Iversen H, Furuseth K. Implementing clinical guidelines in the treatment of diabetes mellitus in general practice. Int J Technol Assess Health Care2000;16:210–27.[ISI][Medline]
  34. Shiffman RN, Liaw Y, Brandt CA, Corb GJ. Computer-based guideline implementation systems: a systematic review of functionality and effectiveness. J Am Med Inform Assoc1999;6:104–114.[Abstract/Free Full Text]
  35. Johnston ME, Langton KB, Haynes B, Mathieu A. Effects of computer-based clinical decision support systems on clinician performance and patient outcome. A critical appraisal of research. Ann Intern Med1994;120:135–42.[Abstract/Free Full Text]
  36. Hunt DL, Haynes RB, Hanna SE, Smith K. Effects of computer-based clinical decision support systems on physician performance and patient outcomes. A systematic review. JAMA1998;280:1339–46.[Abstract/Free Full Text]
  37. Rubenstein LV, Calkins DR, Young RT et al. Improving patient function: a randomized trial of functional disability screening. Ann Intern Med1989;111:836–42.[ISI][Medline]