More is Better in Treating Arthritic Flares

September 2, 2015

Intensifying treatment during flare-ups outweighs concerns about over treatment.

Arthritic flares are par for the course in rheumatoid arthritis. Now a new study conducted over the course of 10 years shows that intensifying treatment during flare-ups outweighs concerns about over treatment. Flare-ups in rheumatoid arthritis can lead to functional disability, pain, morning stiffness and evidence of radiographic progression short and long-term. They can spontaneously resolve so doctors are usually concerned about over-treating flare-ups, however, a new study, published in the August 31 issue of Arthritis Research and Therapy, shows that too little treatment can lead to progressive functional deterioration and joint damage over time. “It seems appropriate to intensify therapy after each flare,” write the authors of the study, which was led by Iris M. Markusse of Leiden University Medical Center in the Netherlands. “Any risk of overtreatment in case of a disease flare that would spontaneously remit may be less serious than the risk of undertreatment resulting in long-term disability and joint damage.”[[{"type":"media","view_mode":"media_crop","fid":"40999","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_2191442379262","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4258","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.0080003738403px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] As previously reported in Rheumatology Network, studies have shown that moderate disease could progress with less aggressive treatment and inflammation can linger even when the patient is thought to be in remission or is experiencing low disease activity. A flare is generally regarded as a worsening of disease activity, including increased morning stiffness and tender and swollen joints and reduced function. However, there’s no accepted definition of a flare in rheumatoid arthritis.  The authors of the new study suggest that continued targeted therapy might reduce the frequency of flares, suggesting that with an adequate treatment strategy, rheumatoid arthritis might become more indolent.  The study is based on an analysis of data from the Dutch BeSt study of 508 rheumatoid arthritis patients who were treated-to-target throughout 10 years. Flares were associated with increases in patient assessment of disease activity, functional deterioration and worsening joint damage seen on X-rays (radiographic progression) – and the more flares a patient had, the worse the outcomes. The protocol called for a change in medication or an increase of dosage if the disease activity in 44 joints score (DAS44) climbed above 2.4 – signalling a rise in swollen and tender joints. After initial treatment adjustments to achieve a DAS44 of 2.4 or below, after the second year of follow, flares were categorized according to three definitions: 

Flare A:  DAS of 2.4 or more with an increase in DAS of at least 0.6 from a previous DAS. These were the most common, affecting 67% of patients (n=321/480) at least once. 

Minor flare B:  DAS greater than 2.4, from a previous DAS ≤2.4 with an increase in DAS <0.6. This occurred at least once in 33% of patients (n = 159/480). 

Major flare B:  The same criteria as minor flare B, but with an increase in DAS of ≥0.6.  This was experienced at least once by 63% of the cohort (n = 304/480).

Treatment adjustments were made based on 3-monthly DAS measurements, targeted at low disease activity (DAS ≤2.4). If DAS was >2.4, medication was intensified. As long as the DAS was ≤2.4 (from at least 6 months), combination therapy was tapered to monotherapy (usually methotrexate monotherapy), and then monotherapy was tapered to a maintenance dose. When DAS was <1.6 for at least 6 months during a maintenance dose, medication was discontinued, but as soon as DAS increased to >1.6, the last effective medication was restarted and, when DAS increased to >2.4, treatment was further intensified. At baseline, patients had active disease with a mean DAS of 4.4 and a mean health assessment questionnaire (HAQ) of 1.4 (0.7). During the first year of follow-up, disease activity was increasingly suppressed. At year 2, patients had a mean DAS of 2.0 (1.0), an HAQ of 0.6 (0.6). And, 320/480 patients (67 %) had achieved a DAS ≤2.4. Over time, during a year where a flare A occurred, the adjusted odds ratio of developing radiographic progression was 1.74 (95 % confidence interval (CI) 1.07–2.85; p = 0.027), compared to no flare. The more flares, the worse patient self-reported function was over 10 years. “Rheumatologists need to be further encouraged to adjust medication each time a flare is registered rather than hope for a spontaneous improvement,” the researchers wrote. “Continued targeted therapy might reduce the frequency of flares, suggesting that with an adequate treatment strategy, RA may become more indolent.” 


Markusse IM, Dirven L, Gerards AH, et al.,

Disease flares in rheumatoid arthritis are associated with joint damage progression and disability: 10-year results from the BeSt study.Arthritis Research & Therapy.

 Aug. 31, 2015. doi:10.1186/s13075-015-0730