How aggressive should initial therapy for rheumatoid arthritis be? Reply

E. L. Matteson, C. M. Weyand1 and J. G. Goronzy1

Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN and 1 Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA, USA

Correspondence to: E. L. Matteson. E-mail: matteson.eric{at}Mayo.edu

We thank Kaarela et al. and Pincus et al. for their comments regarding our experience with a cohort of patients with early rheumatoid arthritis (RA) treated with what most would regard as non-aggressive DMARD therapy [1]. In our study, we noted that after 24 months of follow-up a majority of patients (60%) was either still on solo DMARD therapy with hydroxychloroquine (HCQ) or off DMARD therapy with controlled/quiescent disease. The remaining 40% of patients were taking methotrexate (MTX) (including 11 in combination with other DMARDs). At month 24, 90% of all patients met American College of Rheumatology (ACR) 50 criteria for treatment response.

Kaarela et al. miss the intention and focus of our study. That patients with RA should receive early treatment with DMARDs to prevent disability and other RA related disease complications is undisputed, and was not the subject of this trial. However, the question of how ‘aggressive’ this therapy should be remains to be resolved. There is a significant subset of patients with RA who appear to have a milder disease course and do not require overly aggressive treatment and who, in the current environment, would be unnecessarily subjected to overly aggressive treatment and attendant costs and side-effects, especially with chemotherapeutics and expensive anticytokine therapies. The purpose of this study was to make an attempt to identify this subset of patients.

Kaarela et al. suggest that the Mayo Clinic study will, in effect, watch passively as the patient becomes ‘progressively more crippled before their eyes’. This is incorrect. In fact, our study required systematic observation and therapeutic decision-making based on the ACR50 response criteria. Patients not fulfilling the response criteria had their treatment switched to more aggressive therapy, initially with MTX, according to the treatment protocol.

Kaarela et al. are concerned that we conclude ‘HCQ prevents erosions’. Our study was not a placebo-controlled trial of HCQ effect. The study design was not to test this question, but rather to identify which patients did well on minimal (HCQ) treatment. Clearly a substantial number did.

Kaarela et al. provide a summary of two of their studies, which as many others, demonstrate that aggressive treatment is helpful in RA. We certainly agree that aggressive treatment is indicated in those patients who require it, and may even lead to remission in a variable number of them. Who these patients are is at issue, and is unanswered in their studies. The claim implicit in Kaarela's argument that most patients will develop severe erosive disease appears somewhat contradicted by their own findings. Among 103 patients followed for 20 yr, they detected a high Larsen score or HAQ in 30 (29%), and 16 (15%) of the patients underwent arthroplasty, a perhaps less disputed measure of poor outcome [2]. We do agree that patients who respond poorly have higher rates of work disability and poor outcomes; for this reason our study design mandated more aggressive treatment for patients responding poorly to initial treatment [1].

Pincus et al. also express concerns similar to Kaarela et al., and believe that our patients are undertreated with HCQ. They maintain that the treatment response was inadequate, portending increased disability and joint damage in the future. Again, to the point of our study, our clinical response parameter was the ACR50, with patients being switched to MTX if they failed to meet this pretrial response measure. Whether this response is adequate in terms of long-term disease control is a separate issue this study was not designed to address. Clearly, current thinking is towards complete eradication of any and all signs and symptoms of disease; we agree this is a legitimate goal, which, however, can be achieved with varying means in different patients, not all of whom require ‘aggressive treatment’ [3].

We agree with Kaarela and Pincus et al. that long-term follow up of this and every cohort of patients with RA will provide the true test of adequacy of our current treatment approaches. We hope that a more differentiated approach will identify those patients requiring aggressive treatment, sparing patients with milder disease the unwanted consequences of more aggressive management.

The authors have declared no conflicts of interest.

References

  1. Matteson EL, Weyand CM, Fulbright JW, Christianson TJH, McClelland RL, Goronzy JJ. How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to ‘non-aggressive’ DMARD treatment and perspective from a 2-yr open label trial. Rheumatology 2004;43:619–25.[Abstract/Free Full Text]
  2. Jantti JK, Kaarela K, Belt EA, Kautiainen HJ. Incidence of severe outcome in rheumatoid arthritis during 20 years. J Rheumatol 2002;29:688–92.[ISI][Medline]
  3. Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis 1995;54:944–7.[ISI][Medline]
Accepted 20 July 2004





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