Matrix of Factors Predicts Rapid Progression in Early RA

Janis C. Kelly

December 02, 2019

A matrix of four baseline factors routinely assessed in patients presenting with early rheumatoid arthritis (RA) might help clinicians identify the small proportion who are at risk for rapid radiographic progression (RRP) during the following year despite treatment with methotrexate (MTX) and who might be candidates for more aggressive intervention, researchers report.

"A matrix using the predictors rheumatoid factor [RF] positivity, presence of at least one RA erosion on x-ray, C-reactive protein [CRP] >30 mg/L, and number of swollen joints can identify the very few patients with early RA who are candidates for more aggressive initial treatment than MTX monotherapy," senior author Bruno Fautrel, MD, told Medscape Medical News.

An expert said the matrix just confirms what is already known about these patients, however.

Fautrel is director of rheumatology, Hôpital Pitié-Salpêtrière, Paris, France. The study was published online November 13 in Rheumatology.

Fautrel said the matrix approach would benefit from validation in a randomized controlled trial (RCT) in which a matrix-based strategy is compared against usual step-up therapy to determine the clinical benefit and cost-effectiveness. The matrix could be used now to adjust therapy according to the severity and aggressiveness of RA, he added.

The researchers from France, Austria, the Netherlands, Sweden, and Belgium set out to identify baseline characteristics that could be used in routine clinical practice to identify the relatively small number of disease-modifying antirheumatic drug (DMARD)–naïve patients with early RA who are at risk for RRP. The proportion of high-risk patients with early RA has been estimated at 6% to 20%.

The investigators conducted a post hoc analysis of data from 1306 patients from two cohort studies and three RCTs. The median time from symptom onset to RA diagnosis was 9 weeks.

The follow-up point was 1 year after study entry, and the predictors studied included age, sex, disease duration, RF positivity, anticyclic citrullinated protein antibody level, CRP level, erythrocyte sedimentation rate, swollen joint count (SJC28), tender joint count, presence of at least one erosion on x-ray, and van der Heijde–modified Sharp Score (vSHS). The researchers did not consider smoking status because it was not included in all databases.

The investigators defined RRP as evidence on radiography of an increase of at least 5 points in the vSHS after 1 year.

The final multivariate model, based on data of 1120 patients, included RF status, erosive disease on x-rays, CRP level, and SJC28. The average probability of RRP in the whole study population was 0.21. The matrix was able to differentiate patients who had a 4.1-fold lower-than-average risk from those with a 2.3-fold higher-than-average risk. As might be expected, structural damage at baseline was the strongest single predictor of RRP, followed by RF positivity, CRP, and SJC.

RRP risk increased with the number of matrix factors present. Patients who were RF+ without baseline RA erosions were not at increased risk for RRP regardless of whether other factors were present unless they had 10 or more swollen joints. For those who were RF+ with baseline RA erosions and CRP ≥30 mg/L, RRP risk was 0.37 – 0.47 (vs the average of 0.21) as the number of swollen joints increased from <6 to ≥10.

According to the authors, patients who are RF+ with CRP ≥30 mg/L and baseline erosions are at "high risk" (>1.5-fold average risk) for radiographic progression at 1 year. Those who are RF+ with CRP ≥30 mg/L without baseline erosions are at "intermediate risk" (>1 and ≤1.5-fold average risk) regardless of SJC, as are those who are RF+ with CRP 10–30 mg/L, regardless of SJC. All other patients are at low or very low risk for RRP.

The authors conclude, "Although the matrix has moderate sensitivity and specificity, it is easily usable and may help physicians and patients to make treatment decisions in daily clinical practice."

The study largely just confirms in a more mathematical way what is already widely understood about early RA, rheumatologist Janet E. Pope, MD, told Medscape Medical News. Pope is a professor of medicine in the Division of Rheumatology, professor of epidemiology and biostatistics at the University of Western Ontario, Schulich School of Medicine, and division head in rheumatology at St. Joseph's Health Center, both in London, Ontario, Canada.

"In early rheumatoid arthritis, rapid progression on x-rays is related to inflammation (high CRP, which was very high to increase the chance of finding progressors), many swollen joints, RF seropositivity, and erosions at baseline," she explained. "This doesn't really tell us anything new in the clinic, as an experienced rheumatologist already knows the matrix (more risk factors and higher individual scores increase progression). It may be important for profiling patients and stratifying by these factors in RCTs."

She predicted that this matrix will likely "not get a lot of traction" in routine clinical practice because the majority of patients with early RA do not have sustained high CRP levels, and the proportion of patients who experience RRP is likely closer to 5% to 8%. "We can usually quickly figure out who they are because they don't respond as well to treatment, have high SJC, have high CRP, have baseline erosions, and are RF+, so in clinical practice, a table of risk is likely not needed," Pope said.

For further validation in another cohort of patients with early RA, it would be useful if centrally scored x-rays were used, rather than pooled databases, Pope said.

The study was funded by an unrestricted grant from MSD. Coauthor Nathan Vastesaeger is an employee of MSD. Fautrel received consultancy fees from MSD, Pfizer, and AbbVie. The remaining authors have disclosed no relevant financial relationships.

Rheumatology. Published online November 13, 2019. Abstract

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