Early Aggressive Treatment May Alter Course of Rheumatoid Arthritis

[Guest guest]

Early Aggressive Treatment May Alter Course of Rheumatoid Arthritis

http://www.newswise.com/articles/view/524906/?sc=dwtn

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 Strategies " ) 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. "

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.