Early Aggressive Treatment May Alter Course of Rheumatoid Arthritis

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Early Aggressive Treatment May Alter Course of Rheumatoid Arthritis

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RHEUMATOID ARTHRITIS TREATMENT REMICADE REMISSION

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Early administration of methotrexate and infliximab may lead to

remission in patients with rheumatoid arthritis, according to

research presented this week at the American College of Rheumatology

Annual Scientific Meeting in Washington, DC.



Newswise — Early administration of methotrexate and infliximab may

lead to remission in patients with rheumatoid arthritis, according to

research presented this week at the American College of Rheumatology

Annual Scientific Meeting in Washington, DC.

Methotrexate and the injectable infliximab are among several disease-

modifying antirheumatic drugs administered to reduce or prevent joint

damage as well as preserve joint integrity. These drugs, often used

in conjunction with non-steroidal anti-inflammatory drugs like

ibuprofen, have greatly improved symptoms, function and quality of

life for patients with rheumatoid arthritis.

Dutch rheumatologists, conducting a long-term BeSt (“Behandel

Strategieën†or “Treatment Strategiesâ€) study on 508 patients

with early evidence of the rheumatoid arthritis, explored four

strategies for treatment utilizing various combinations of these

DMARDS. These strategies included: sequential monotherapy,

monotherapy building up to combination therapy, and initial

combination therapy using either prednisone or infliximab. All

patients who started infliximab also were on methotrexate. In the

case of adverse drug events requiring the discontinuation of

methotrexate, an alternative DMARD (usually sulfasalazine) was

started in combination with infliximab.

The initial combination therapies proved superior to initial

monotherapy in gaining earlier improvement in functional ability and

decreasing radiographic joint damage progression. After two years,

56% of patients treated with the initial combination of methotrexate

and infliximab were able to discontinue infliximab without relapse,

and subsequently taper methotrexate to 10 mg/week. A year later, 14%

of all patients receiving initial treatment with infliximab tapered

off all medication and are still in remission (no measurable signs of

disease activity). Only four patients (out of the original 67

responders at two years) who were on methotrexate 10 mg/week had to

increase methotrexate to 25 mg/week and restart infliximab during the

third year because of a flare in disease activity.

Currently, the BeSt study includes the only large cohort of patients

with early rheumatoid arthritis who have successfully discontinued

infliximab after achieving low disease activity. Given many

patients’ ability to achieve remission after two years and taper

medication to methotrexate 10 mg/week, BeSt researchers had added the

goal of discontinuation to third-year follow-up.

“These three-year follow-up results indicate that initial treatment

with methotrexate and infliximab may alter the course of early

rheumatoid arthritis and, in many cases, move patients into

remission,†summarizes Sjoerd van der Kooij, MD, Leiden University

Medical Center, Leiden, The Netherlands, an investigator in the

study. “Data collected over the next years will determine whether

treatment-free remission will last, and whether it represents not

only clinical but also radiological suppression of disease activity.â€

The American College of Rheumatology is the professional organization

for rheumatologists and health professionals who share a dedication

to healing, preventing disability and curing arthritis and related

rheumatic and musculoskeletal diseases. For more information on the

ACR’s annual meeting, see http://www.rheumatology.org/annual.

Presentation Number: 658

Remission Induction in Early Rheumatoid Arthritis (RA) with Initial

Infliximab (IFX) and Methotrexate (MTX) Therapy: The Disease Course

After IFX Discontinuation in The BeSt Trial

S. M. Van Der Kooij1, A. E. Van Der Bijl1, C. F. Allaart1, Y. P.M.

Goekoop-Ruiterman1, J. K. De Vries-Bouwstra2, A. H. Gerards3, M. L.

Westedt4, F. C. Breedveld1, B. A.C. Dijkmans2. 1LUMC, Leiden, The

Netherlands; 2VUMC, Amsterdam, The Netherlands; 3Vlietland, Schiedam,

The Netherlands; 4Bronovo, The Hague, The Netherlands

PURPOSE

To describe the clinical and radiological outcome of patients with

early RA who discontinued IFX after good clinical response on initial

treatment with IFX+MTX.

METHODS

In the BeSt study, a randomized clinical trial comparing 4 different

treatment strategies in early RA, 120 patients in Group 4 (baseline

DAS 4.3, 64% rheumatoid factor positive, 73% erosive) started

treatment with IFX 3 mg/kg plus MTX 25 mg/week. If the DAS,

calculated 1-2 weeks before each IFX infusion, was >2.4, IFX was

increased (6, 7.5 and max. 10 mg/kg/8 weeks). If DAS was =<2.4 for >=

6 months, IFX was tapered to nil and next MTX was tapered to 10 mg/

week. In the 3rd year, if DAS was <1.6 for >= 6 months, MTX 10 mg/wk

was tapered to nil. If the next DAS was >1.6, MTX 10 mg/week was

restarted, then, if the DAS was >2.4, first MTX was increased to 25

mg/week, next IFX was restarted and if necessary increased. Baseline

and 3-year Sharp-van der Heijde Scores (SHS) were assessed

independently in random order by 2 physicians.

RESULTS

After 2 years, 67/120 patients (‘Responders’, 56%) had

successfully discontinued IFX and tapered MTX to (mean) 12.6 mg/week;

23/120 patients were on variable IFX dosages ('Continued Treatment')

and 30 patients had failed on IFX+MTX and switched to other treatment

steps.

After 3 years, median 26 months after IFX discontinuation, 61/67

(91%) of the 'Responders' (51% of all 120 patients) still had DAS

=<2.4, and of these, 16 were in remission without any anti-rheumatic

therapy; 45 were on MTX (mean dose 12 mg/week), and 2 on

sulphasalazine (SSA) (because of wish for pregnancy). Four

'Responders' had restarted IFX, median 22.5 (19.1-26.9) months after

discontinuation. Of the 23 'Continued Treatment' patients, 3 failed

IFX+MTX therapy and switched to SSA in the 3rd year, 3 stopped IFX

after DAS =<2.4 for >= 6 months (1, 5 and 8 months without IFX at t=3

years; 1 patient also stopped MTX) and 17 remained on IFX (mean dose

5.5 mg/kg) with MTX.

Mean SHS progression after 3 years was 2.5 in Responders, 4.7 in

Continued Treatment and 6.2 in Failures. Responders who could

discontinue all anti-rheumatic therapy showed no radiographic

progression. At baseline these patients had active RA (mean DAS 4.3),

59% had erosive disease.

CONCLUSIONS

Three years after starting treatment with IFX and MTX, 53% of the

patients with early RA had discontinued IFX and still had DAS =<2.4.

Of these 64 patients, 17 (27%) remained in clinical remission after

stopping all anti-rheumatic drugs, without showing progression of

joint damage. These findings indicate that initial treatment with MTX

+ IFX may alter the course of early RA.

Disclosure Block: S.M. Van Der Kooij, Dutch College For Health

Insurances, 2 Research grants; Centocor Inc., 2 Research grants;

Schering-Plough B.V., 2 Research grants.

http://www.newswise.com/p/articles/view/524906/