Moderate Treatment Not Enough to Curb Moderate Arthritis

Pam Harrison

June 26, 2015

ROME — In the first 5 years after the onset of rheumatoid arthritis, the risk for major joint surgery is the same for patients with moderate disease activity and those with persistently high levels of disease activity, new research warns.

"It is well established that sustained high disease activity in rheumatoid arthritis results in worse outcomes," Elena Nikiphorou, MD, from St. Albans City Hospital in the United Kingdom, said in a statement.

However, "our data provide an argument for updating existing disease activity cutoff points to all patients with moderate disease activity so they can receive a biologic agent in addition to conventional disease-modifying antirheumatic drugs [DMARDs]," she explained here at the European League Against Rheumatism Congress 2015.

The 2071 study participants were recruited from the Early RA Study and the Early Rheumatoid Arthritis Network. Of these, 2044 patients had at least two disease activity scores documented from year 1 after disease onset to year 5.

Treatment regimens reflected guidelines of the era, and were mainly conventional DMARDs and, in more recent years, biologics.

The need for orthopedic surgery during the first 5 years was used as a surrogate marker of joint destruction and failure of treatment. There were 1602 surgical interventions in the study cohort during the follow-up period.

Interventions were categorized as major for large joint replacement; as intermediate for synovectomy, joint fusion, and excision arthroplasty of the wrist, hand, hind, or forefoot; and as minor for soft tissue surgery.

Investigators calculated mean disease activity from year 1 after disease onset to year 5 for each patient.

Table 1. Level of Activity by Disease Activity Score

Score Level of Activity
<2.6 remission
2.6 to 3.19 low
3.2 to 4.19 low-moderate
4.2 to 5.1 high-moderate
>5.1 high


The risk for major joint surgery in the first 5 years after disease onset was higher in patients with low-moderate, high-moderate, and high disease activity than in patients with low disease activity, after confounding variables such as age at disease onset, sex, and symptom duration were controlled for.

Table 2. Risk for Major Joint Surgery, Relative to Low Disease Activity

Disease Activity Hazard Ratio 95% Confidence Interval P Value
Low-moderate 2.07 1.28–3.33 <.005
High-moderate 2.16 1.32–3.52 <.005
High 2.48 1.50–4.11 <.005


The risk for intermediate joint surgery in the first 5 years after disease onset was 80% higher in patients with high-moderate disease activity than in those with low or low-moderate activity (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.05 - 3.11; P = .034).

In addition, the risk was 2.5 times higher in patients with high disease activity than in those with low activity (HR, 2.59; 95% CI, 1.49 - 4.52; P = .001).

"Our conclusion from this study is that patients with rheumatoid arthritis with moderate disease activity levels in the first 5 years of disease onset, despite treatment with conventional DMARDs, are at similar risk for large joint surgery as those with high disease activity," Dr Nikiphorou said.

Therefore, "aiming to keep patients in the low disease-activity state is important for long-term outcomes," she explained.

To be treated with a biologic DMARD in the United Kingdom, disease activity must be high on at least two occasions at least 1 month apart, she told Medscape Medical News. In addition, patients must have tried at least methotrexate and one other conventional DMARD for 6 months before a biologic can be initiated.

Dr Nikiphorou and her colleagues previously showed that patients with moderate disease activity have greater functional progression of disease, measured on the Health Assessment Questionnaire, and a greater risk for radiographic progression in the first 5 years after disease onset than those with low disease activity.

"People with moderate disease activity are clearly progressing," she said. "It might be that it's subclinical, but they are silently progressing."

Real-Life Data

"The real problem is that we are not allowed to give patients with moderate disease activity more intensive treatment, like a biologic, in countries like the United Kingdom," Dr Nikiphorou pointed out. "I am hoping this kind of work will inform national recommendations and guidelines."

These real-life data demonstrate the importance of the treat-to-target strategy as the standard of care in rheumatoid arthritis, said session cochair Ernest Choy, MD, from the Cardiff University School of Medicine in the United Kingdom.

Given that these data are from the United Kingdom, where high disease activity "is one of the criteria needed for initiating biologic treatment, the cost-effectiveness of biologic therapy in moderate disease activity in rheumatoid arthritis needs to incorporate these data to prevent joint surgery in this patient population," Dr Choy told Medscape Medical News.

Dr Nikiphorou and Dr Choy have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2015: Abstract OP0179. Presented June 12, 2015.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.