Treatment-to-target strategies decreased pain for children with non-systemic JIA

Treatment-to-target strategies decreased pain for children with non-systemic JIA | Image Credit: © vectorwin - © vectorwin - stock.adobe.com.

In non-systemic juvenile idiopathic arthritis (JIA) patients, a treatment-to-target approach was effective in reducing pain, irrespective of initial treatment strategy, according to a study published in Pediatric Rheumatology.

The most common autoimmune disease in children, JIA is prevalent in an estimated 33 out of every 100,000 children. The pain associated with JIA can cause sleep disturbances, a decline in quality of life, and school attendance issues.

According to study authors, the introduction of biologic disease-modifying antirheumatic medicines (DMARDs) earlier in disease course has improved outcomes for JIA patients in recent years. This improvement is not directly translated into better pain outcomes however, as some children experience pain during inactive disease even with adequate treatment and effective disease control.

A decreased pain threshold could be a possible explanation for persistent pain for children with low or no visible disease activity. Compared to healthy children, those with JIA were found to have a lower threshold for pain, even with no detectable joint inflammation after treatment. Longer disease duration could be a possible predictor.

Authors note it has been hypothesized that peripheral and central sensitization can contribute to a lower pain threshold because of prolonged hypersensitivity of pain circuits in the nerve system. As a result of this, the authors noted that pain should be treated “as soon and adequately as possible to prevent sensitization,” according to the study.

Study investigators sought to compare pain scores over 2 years in 3 treatment strategies in non-systemic JIA patients who were treated to target aimed at inactive disease, and to determine the effect of inactive disease and time to inactive disease on pain. Baseline characteristics for predicting unfavorable pain trajectories were also explored.

The BeSt for Kids study, a Dutch, multicenter, randomized, single-blinded trial, was designed to investigate effectiveness of 3 different treat to target strategies for non-systemic JIA patients aged 2 to 16 years with newly diagnosed JIA. Disease duration of more than 18 months, uveitis at enrollment, and prior DMARD therapy were exclusion criteria.

Randomized between 3 strategy arms, patients either were initially treated with methotrexate (MTX) or sulfasalazine (SSZ) monotherapy (arm 1), initially received MTX and 6 weeks prednisolone bridging (arm 2) or were initially treated with etanercept (ETN) and MTX (arm 3).

Patients were treated to target, with inactive disease as treatment goal. Treatment was intensified if inflammation was not suppressed enough, and inactive disease was not achieved. Patients were followed for every 3 months for up to 2 years and treatment was tapered and stopped after at least 6 months of inactive disease.

The primary endpoint of the study was pain intensity, assessed by using a 100 mm visual analogue scale (VAS). Patients were asked to rate their pain using the scale over 7 days, where 0 mm is “no pain,” and 100 mm is “unbearable pain.” A VAS pain of 35 mm or less was considered “mild pain,” a pain of 36 to 60 was “moderate pain,” and “severe pain” was 61 mm or more. Parents estimated pain levels for children younger than 12 years.

In all, 94 patients were randomized between 2009 and 2014. Thirty-two were assigned to arm 1, 32 to arm 2, and 30 in arm 3. Over time, pain scores reduced from mean 55.3 to 19.5 after 2 years. Scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month on average.

There were no significant difference found in pain over 2 years between treatment arms and correction for age and sex yielded similar results. Across the 2 years, more than 70% of patients reached inactive disease, and the effect of inactive disease on VAS pain was β -16.87 mm (95% CI -19.65; -14.10) for inactive versus active disease, according to the authors.

A higher VAS pain (β 0.44 [95% CI 0.25; 0.65]) and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time. With a β of 0.46 (95% CI, 0.25-0.65), every additional 10 mm VAS pain at baseline was associated with a 4.6 mm higher VAS pain during follow up.

The study authors concluded that target therapy is effective in reducing pain over time for DMARD- naïve, non-systemic JIA patients, regardless of initial treatment. However, some children still experienced pain despite achieving clinically inactive disease. According to the authors, “this emphasizes the necessity of addressing patient related outcomes in addition to targeted treatment to reduce disease activity.”

Reference:

Spekking K, Anink J, de Boer P, et al. Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target: results over 24 months of follow up. Pediatric Rheumatology. 2023;21(1):90. doi:10.1186/s12969-023-00874-z