Combination of Methotrexate and Prednisone Produces Remission In People with Newly-Developed Rheumatoid Arthritis and Undifferentiated Arthritis

• Arthritis • • Rheumatic Diseases • Nov 08, 10

People with newly-developed rheumatoid arthritis or undifferentiated arthritis may be able to achieve remission, with continued drug therapy, after four months of treatment with methotrexate and prednisone, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. The new ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria are based on the recognition that undifferentiated arthritis may be the earliest clinical manifestation of RA.

Researchers recently assessed whether people with RA (which had developed less than two years before the start of the study) or undifferentiated arthritis (defined, for this study, as having arthritis in more than one joint and being considered at risk for developing RA) could achieve remission after four months of taking a combination of methotrexate and prednisone.

Throughout the course of the study, researchers followed 261 people with RA and 161 people with undifferentiated arthritis who were taking 25 mg per week of methotrexate and 60 mg per day of prednisone, which was tapered down to 7.5 mg per day over the course of seven weeks.

According to C. F. (Renée) Allaart, MD, PhD—associate professor of rheumatology at Leiden University Medical Center in Leiden, The Netherlands, and an investigator in the study—this is first study to treat early RA and undifferentiated arthritis patients with progressive combination therapy, which was previously reserved for active, more advanced RA. The goal was to see if participants could achieve remission based on a Disease Activity Score under 1.6. Researchers measured this clinical outcome and considered functional abilities when making their final assessments of the success of the combination of methotrexate and prednisone.

They found that remission was achieved in 153 (58.6 percent) of the participants with RA and 107 (66.5 percent) of the participants with undifferentiated arthritis. Althogether, the disease went into remission in 63 percent of patients. There was improvement in the average DAS scores of participants of 1.90 for participants with RA, and 1.32 in participants with undifferentiated arthritis. There was also an improvement in overall functionality reported by participants in both groups. Participants in both groups who began the study with lower DAS scores were more likely to achieve remission after four months of the combined treatment.

“The results show that—in this group of patients with earlier, and on average less active RA—remission percentages are higher than with similar treatment in more active RA, and that the addition of high-tapered-to-low prednisone to methotrexate works in undifferentiated arthritis,” says Dr. Allaart, noting that previously published early remission rates for active RA are less than 30 percent (depending on initial treatment). “We now will try to taper and stop the medication in order to achieve drug-free remission.”

This ongoing study will continue to report on the patients who achieved remission and had their medications discontinued. More than 600 patients have now been included, and the study will begin a second phase where participants with RA and undifferentiated arthritis who have not achieved remission while taking methotrexate with prednisone are randomly placed in two treatment groups. One group will be given multiple disease-modifying antirheumatic drugs (such as methotrexate, sulfasalazine, hydroxychloroquine, and low-dose prednisone), while the other group will be given an anti-TNF (adalimumab) with methotrexate. The aim remains to achieve (ultimately drug-free) remission.

“The results of the randomized, second phase of the study will determine whether there is still a place for conventional DMARD therapy after failure on methotrexate and prednisone, or whether anti-TNF is the best option for early remission induction treatment,” Dr. Allaart says.

For now, she suggests the optimal strategy is to start treatment early and aim at remission. “A short initial course of prednisone, even at a relatively high dose, is probably preferred over delayed but long-term low prednisone dosages in patients with RA,” she says. “We found that even with relatively mild or little joint involvement, patients are motivated to take progressive medication in order to achieve early remission.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.rheumatology.org/education. Follow the meeting on twitter by using the official hashtag: #ACR2010.

Editor’s Notes: K V C de Boer will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:30 PM on Tuesday, November 9 in the Sidney J. Marcus Auditorium. Dr. Allaart will be available for media questions and briefing at 8:30 AM on Monday, November 8 in the on-site press conference room, B 212.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover how the ACR Research and Education Foundation’s Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign is accelerating RA research.

Presentation Number: 1396

Induction Therapy with Methotrexate and Prednisone in Rheumatoid or Very Early Arthritic Disease: IMPROVED Study.

K V C de Boer (LUMC, Leiden, Leiden)
K Visser (LUMC, Leiden, Leiden)
H K Ronday (Haga Hospital, the Hague)
A A Schouffoer (Groene Hart Hospital, Gouda)
J H L M Groenendael (Franciscus Hospital, Roosendaal)
A J Peeters (Reinier de Graaf Gasthuis, Delft)
I Speyer (Bronovo Hospital, the Hague)
G Collée (MCH, the Hague)
P B J Sonnaville (Oosterschelde Hospital, Goes)
B A M Grillet (Zorgsaam, Terneuzen)
T. W J Huizinga (LUMC, Leiden, Leiden)
C F Allaart, MD, PhD (LUMC, Leiden, Leiden)

Aim: To assess the rate of remission after 4 months of treatment with methotrexate (MTX) and a tapered high dose prednisone in patients with recent onset rheumatoid or undifferentiated arthritis (RA and UA), in relation to clinical and demographic baseline criteria.

Methods: IMPROVED is a multicenter single blind clinical study in patients with recent onset RA and UA, with an open label induction phase with MTX 25 mg/wk and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks, aimed at achieving DAS

< 1.6, which will be followed by tapering to drug free if remission persists, or randomization to multi-DMARD or MTX + adalimumab if DAS ≥ 1.6 after 4 months. To date, 161 patients with UA (arthritis >

1 joint, at risk for developing RA by estimation of a rheumatologist) and 261 patients with recent onset RA (ACR 1987 criteria, symptom duration < two years) were included. Clinical outcomes (% remission DAS <1.6) and functional ability measured with the Dutch Health Assessment Questionnaire (HAQ) after 4 months of treatment were compared between RA and UA patients. Independent predictors at baseline for achieving remission after 4 months were established by univariable followed by multivariable regression analysis.

Results: At baseline, UA patients were younger, less often RF positive and had lower DAS, HAQ and ESR values, than RA patients (table 1). After four months of treatment, clinical remission was achieved in 107/161 UA patients (66.5%) and in 153/261 RA (58.6%) (P = 0.12). Improvement in mean DAS was 1.32 (0.95) in the UA patients and 1.90 (1.05) in the RA patients (P < 0.001), improvement in mean HAQ was 0.57 (0.65) and 0.81 (0.65), respectively (P < 0.001) (table 1). Low baseline DAS was predictive for achieving remission after 4 months in both UA and RA (OR 0.36, 95% CI 0.18-0.67). In UA patients, but not in RA patients, other predictors for achieving clinical remission were male sex (OR 2.76, 95% CI 1.13-6.73) and ACPA-positivity (OR 2.83, 95% CI 1.07-7.51)

Conclusion: After 4 months of treatment with MTX and a tapered high dose of prednisone in patients with recent onset RA or UA, clinical remission (DAS < 1.6) was achieved in 63% of all patients, with similar outcomes for mean DAS and HAQ. Only in UA patients, ACPA positivity is an independent predictor for achieving remission. This suggests that ACPA negative UA patients, who did not benefit from treatment with MTX monotherapy in the PROMPT study, also benefit less from prednisone. ACPA negative UA may be a different disease that requires different therapy than ACPA positive UA.

Disclosure: K de Boer, Abbott Laboratories: Research grants; K Visser, nothing to disclose; H Ronday, nothing to disclose; A Schouffoer, nothing to disclose; J Groenendael, nothing to disclose; A Peeters, nothing to disclose; I Speyer, nothing to disclose; G Collée, nothing to disclose; P Sonnaville, nothing to disclose; B Grillet, nothing to disclose; T. Huizinga, nothing to disclose; C Allaart, nothing to disclose.

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Source: American College of Rheumatology (ACR)