Sustained benefit from early RA treatment with multiple DMARDs

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Sustained benefit from early RA treatment with multiple DMARDs

Rheumawire

Jul 29, 2004

Janis

Tampere, Finland - " Early, aggressive treatment with a 3-drug DMARD

regimen significantly retards joint damage (vs a single DMARD), and this

advantage persists even when many of the original single-drug patients

switch to combination DMARDs after 2 years, " Dr Markku Korpela tells

rheumawire. Korpela and colleagues in the Finnish Rheumatoid Arthritis

Combination Therapy (FIN-RACo) study report 5-year follow-up data in the

July 2004 issue of Arthritis & Rheumatism [1].

" The results of the FIN-RACo trial showed that radiologic progression

during the first 2 years as significantly reduced not only in peripheral

joints but also in the cervical spine of patients treated according to

the combination [DMARD] strategy compared with those treated according

to the single [DMARD] strategy. The results of the present follow-up

study demonstrate convincingly that radiologic progression continued to

be significantly retarded (actually by 33%) at 5 years in RA patients

originally allocated to the combination strategy, compared with those

treated according to the single strategy, despite the lifting of

restrictions on DMARD treatment after 2 years, " Korpela et al write.

The FIN-RACo study is a prospective, randomized trial comparing the

efficacy and tolerability of a combination of 3 DMARDs with that of

DMARD monotherapy in patients with early active RA. The 2-year follow-up

study comprised 178 patients. " The main purpose of this study was to

determine whether the relatively high frequency of remissions and slower

deterioration of joint damage obtained by the combination therapy at 2

years were sustained despite the unrestricted choice of drug therapy

thereafter, " Korpela writes.

The trial enrolled DMARD-naïve patients with RA symptom duration of less

than 2 years (median 6 months). Patients were randomized to a single

DMARD (initially, sulfasalazine with or without prednisolone) or to

simultaneous sulfasalazine, methotrexate, and hydroxychloroquine, with

prednisolone. None of the patients in this study were taking biologicals

such as tumor-necrosis-factor (TNF) inhibitors.

" In Finland, we use biologicals like infliximab when combination DMARDs

[such as those used in FIN-RACo study] are ineffective and polyarthritis

is active [there are at least 6 tender and swollen joints, and

acute-phase reactants are elevated], " Korpela explains.

Patients continued treatment as assigned in these 2 parallel groups for

2 years, after which choice of treatment was unrestricted. Treatment was

allowed to be tapered for patients in remission. Clinical activity was

determined by the Disease Activity Score in 28 joints (DAS28). Hands and

feet were radiographed yearly and scored according to the Larsen method.

Remission was defined according to American College of Rheumatology

(ACR) criteria, excluding the criteria for fatigue. All 5 of the

remaining ACR criteria had to be fulfilled to meet the standard for

remission.

At 5 years, 9 of 87 patients who completed 2 years of treatment in the

" combined-DMARD " group and 9 of 91 patients in the " single-DMARD " group

were lost to follow-up, and Korpela presented data for 160 patients (78

in the combination group and 82 in the single group).

As might be expected, after the 2 years of required treatment, most

patients in the combined-DMARD group continued combined treatments, but

most of the patients in the single group switched to a DMARD

combination. " DMARD treatment was free (unrestricted) after 2 years, ie,

rheumatologists were allowed to adjust medications to achieve remission.

Of the original combination group, 70 (90%) continued to receive

combinations after 2 years, and 51 of the 82 patients in the original

single group (62%) received combinations after 2 years, " Korpela says.

This did not, however, enable those who began with single-agent

treatment to make up for lost time. The increase in median Larsen score

was significantly slower during the first 2 years in the

combination-DMARD patients and remained " consistently lower " in those

patients up to 5 years, despite the fact that many of the patients in

the comparison group switched to triple DMARD regimens after year 2.

According to Korpela, the expected rate of spontaneous remission in

untreated RA is about 14%, and the rate of remission with conventional

single-DMARD therapy is about 18%.

" In the present FIN-RACo study, the rate of remissions at 2 years was

40% in DMARD-naïve patients with early RA treated with combinations of 3

DMARDs for the first 2 years. However, the lifting of treatment

restrictions after 2 years resulted in a decrease in the rate of

remissions (28% at 5 years. . . . The results imply that the revocation

of therapy with combinations of DMARDs after 2 years was not prudent,

since the high remission rate was partly lost, " Korpela writes. " [T]he

'late' institution of DMARD combinations (after 2 years from the time of

diagnosis) does not increase the rate of remissions in patients who are

initially treated with a single DMARDthat is, the therapeutic 'window of

opportunity' appears to be lost in most of these patients. "

Ordered logistic regression analyses showed that the extent of joint

damage in the hands and feet at 5 years was predicted most strongly by

the presence of serum rheumatoid factor at baseline (odds ratio 2.75)

and by single-DMARD treatment for the first 2 years (OR 2.53). " Despite

aggressive treatment of RA, rheumatoid factor still remained a very

significant predictor of radiologic progression at 5 years, " Korpela

says.

Korpela comments that the use of " new, very expensive " biologic

antirheumatic drugs has become routine over the past few years.

" Prospective studies comparing the effects, including the

cost-effectiveness, of combinations of traditional DMARDs with the

effects of biologic drugs in patients with early RA are urgently

needed, " Korpela says.

Other unanswered questions include whether combination DMARDs should be

continued in patients in clinical remission and for how long and whether

there is a subgroup of patients who will need biologicals in addition to

the FIN-RACo DMARD combination in the early phases of RA.

" Our results suggest that 3-drug treatment should be started in most

patients with early RA at the time of diagnosis. However, if the DMARD

therapy can be started within 4 months from the first symptoms of RA, a

high proportion of remissions can be achieved also by single-DMARD

therapy. If the delay in the institution of DMARDs was more than 4

months, the high proportion of remissions is achieved only by

combination treatment strategy, " Korpela tells rheumawire.

Source

Korpela M, Laasonen L, Hannonen P, et al. Retardation

of joint damage in patients with early rheumatoid arthritis by initial

aggressive treatment with disease-modifying antirheumatic drugs.

Arthritis Rheum 2004; 50:2072-2081.

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