AMSTERDAM, The Netherlands – Prompt dosing with methotrexate (MTX) can change the prospects of many patients with early, undifferentiated arthritis and should be considered in all such patients who are positive for anti-citrullinated peptides (anti-CCP) antibodies or for rheumatoid factor (RF), Tom Huizinga, MD, of Leiden University Medical Center in Leiden, the Netherlands, told a press conference at the 2006 EULAR meeting. Dr. Huizinga is a co-investigator in the study, which was presented by lead investigator Henricke Van Dongen, MD, also of Leiden University Medical Center.1

"We don't know if this is only a retardation or whether it might prevent RA, but it is fantastic news from the patient's perspective." —Tom Huizinga, MD
"The data show that fewer patients treated with MTX had developed rheumatoid arthritis [RA] compared with the placebo group at 1 year. We don't know if this is only a retardation or whether it might prevent RA, but it is fantastic news from the patient's perspective. Early MTX treatment was able to postpone RA for almost a year in anti-CCP-positive patients," Dr. Huizinga said.

These conclusions were based on data from the Probable Rheumatoid Arthritis Methotrexate versus Placebo Therapy (PROMPT) study, a prospective double-blind placebo-controlled randomized multicenter trial in 110 patients with undifferentiated arthritis (UA) who fulfilled the ACR 1958 criteria for probable RA. Patients were randomized to weekly treatment with either MTX 15 mg/wk or the same number of placebo tablets. The primary endpoint was the Disease Activity Scale, which was measured every 3 months. The treatment goal was to achieve and maintain a DAS28 of 2.4. Study medication was tapered to nil after 12 months. Patients who progressed to meeting the ACR 1987 criteria for RA at any point were treated with MTX. Radiographic joint damage of hands and feet was scored every 6 months. Anti-CCP status was determined at the end of the study.

Dr. Van Dongen reported that significantly fewer patients In the MTX group progressed to RA (20 versus 29, P =.02) and that more MTX-treated patients reached remission (18 versus 11, P =.02). Patients with erosive disease particularly benefited from MTX, with a significant retardation of radiographic progression (P = .035).

However, Dr. Huizinga explained that most of the MTX treatment benefit was confined to patients who were anti-CCP. He said that considering the group as a whole, there was no significant difference in radiographic progression with MTX vs placebo. "If we treat everyone, we would be heavily overtreating patients," he warned.

Anti-CCP-positive patients seem to benefit most from treatment with MTX, which the investigators say indicates "the existence of a window of opportunity in anti-CCP-positive arthritic patients to influence the disease progression into full-blown RA. This is the first RCT that demonstrates the existence of such a window of opportunity," they note.

While anti-CCP is commonly used in Europe, it is less often ordered by physicians in the US. Dr. Huizinga told CIAOMed that other data show a similar divergence of response in patients who are RF-positive vs those who are RF-negative, and that RF can similarly be used to identify patients with undifferentiated early arthritis whose "window of opportunity" is open.

Reference

  1. Van Dongen H, et al. Probable rheumatoid arthritis methotrexate versus placebo therapy (PROMPT) study: indications for a window of opportunity in the treatment of patients with undifferentiated arthritis. Presented at: EULAR 2006 Meeting; June 21–14, 2006; Amsterdam, the Netherlands. Abstract OP0001.