Most early-RA patients do fine with nonaggressive hydroxychloroquine DMARD treatment

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May 13, 2004

Most early-RA patients do fine with " nonaggressive " hydroxychloroquine DMARD

treatment

Rochester, MN - An open-label trial aimed at identifying baseline factors

associated in rheumatoid arthritis (RA) patients with good response to an

initial mild treatment regimen showed that more than half of patients with

early RA did very well on hydroxychloroquine (HCQ) over 2 years and that the

class I MHC gene marker HLA-C7xx might be a new marker for patients likely

to require more aggressive treatment [1].

" All patients with RA should receive DMARD therapy, and even 'mild' DMARD

therapy such as hydroxychloroquine has significant disease-ameliorating

effects. "

Lead author Dr L Matteson (Mayo Clinic, Rochester, MN), tells

rheumawire, " It is important to recognize that RA is a disease with

heterogeneous phenotype, that treatment should be tailored to the patient,

and that many patients do well with less-aggressive regimens. What is of key

importance is that all patients with RA should receive disease-modifying

antirheumatic drug (DMARD) therapy and that even 'mild' DMARD therapy has

significant disease-ameliorating effects. "

Goal: find the patients who don't need aggressive therapy

" Identification of patients who are destined to have a rather benign disease

course and may not need aggressive treatment would not only protect these

patients from excessive treatment with its attendant potential toxicity but

would also have socioeconomic implications, " the authors write.

The open-label, 2-year study to address this issue enrolled 111 consecutive

patients with RA of duration less than 1 year. The investigators developed a

standardized treatment algorithm designed to avoid initial overtreatment

while permitting treatment escalation to achieve symptom control in patients

with persistently active disease. The primary outcome measure was

radiographic change at 2 years.

None of the patients had previously received any standard DMARD, including

gold, HCQ, methotrexate, sulfasalazine, or any of the newer drugs. All

patients first received HCQ 200 mg bid and then, if needed, a nonsteroidal

anti-inflammatory drug (NSAID). Low-dose prednisone (<10 mg/day) was

permitted if needed for initial disease control. HCQ was changed to

methotrexate (7.5-20 mg/wk, with 1 mg/day of folic acid) if the response to

initial treatment failed to fulfill a preset definition of treatment

response. Other DMARDs could then be added or substituted if the patient

responded poorly to methotrexate. Patients needing more than 10 mg/day of

prednisone were considered nonresponders. Treatment response was defined by

American College of Rheumatology (ACR) 50 criteria.

Disease activity was assessed at 6, 12, and 24 months, including painful and

swollen joint count, Westergren sedimentation rate, patient and physician

global assessments, pain assessment, duration of morning stiffness,

patient-derived functional assessment with the Health Assessment

Questionnaire for RA (HAQ), and presence of extra-articular disease

manifestations. Of 111 patients, 94 completed the 2-year study.

At 2 years, 56% of patients doing fine on HCQ or nothing

At 24 months, 52% of patients (49/94) remained on HCQ with well-controlled

disease, and 4% (4/94) were off treatment but still with control of disease.

Of the patients, 40% (38/94) had been switched to methotrexate (average dose

16.25 mg/wk), including 11 patients who at 24 months were taking

methotrexate in combination with another DMARD.

" We were surprised at how many patients did well. "

" We were surprised at how many patients did well, " Matteson admits.

Twenty-eight patients (25%) had been on oral prednisone at baseline. The

drug was continued in 11, discontinued in 13, and for 4 patients there was

no information. Among prednisone users, the dose was lower at month 24 than

at baseline, and only 7 of the 49 patients who were responders at month 24

were still taking prednisone (mean dose 3.4 mg/day).

As might be expected, most patients in this early-RA group (74%) had no

RA-specific radiographic damage at baseline. Matteson reports that on

average patients had about 1 additional erosion in wrist,

metacarpophalangeal, or proximal interphalangeal joints during the 2-year

observation period.

" The dynamics of progression of erosion were nearly identical in the

patients remaining on HCQ and those taking methotrexate or other DMARD at

month 24, suggesting that clinical response, even if restrictively defined,

did not predict radiographic outcome after 2 years, " he writes.

Several factors were examined as possible predictors of the need for more

aggressive DMARD treatment. Only the presence of HLA-C7xx and/or high HAQ

pain score at baseline identified patients likely to require more aggressive

DMARD treatment. " The association of this class I MHC gene has not been

previously identified as a marker of RA severity, " the investigators note.

New marker of high-risk disease?

" A very substantial percentage of patients can be successfully managed with

this relatively mild regimen, " Matteson says. He adds that this raises the

concern that the recent move toward early, aggressive DMARD treat might be

leading to overtreatment in many patients.

" We were also interested to find that the class I HLA-C7 was a predictor of

need for more aggressive treatment. We are currently trying to identify what

role this gene may play in the disease and to determine whether this finding

will be substantiated in further studies. "

If so, it will joint the small group of other indicators of high-risk

disease, including positive rheumatoid factor, poor patient global

assessment, high pain score, and higher number of swollen joints.

Janis

Source

1. Matteson EL, Weyand CM, Fulbright JW, et al. 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 (Oxford) 2004 May; 43(5):619-25.