In individuals with rheumatoid arthritis (RA), the patient-reported outcomes (PROs) such as pain, function, fatigue, and global disease assessment may have higher sensitivity to treatment response than physician-reported outcomes and clinical criteria. For example, patient-reported functional status has been found to surpass clinical and laboratory assessments as the top predictor of mortality in RA.¹

In a recent study funded by AbbVie Deutschland GmbH & Co. KG, researchers aimed to determine the degree of change required for significant responses in these PROs and investigated the relationship between treatment response and improvement in PROs. Their findings were published in Arthritis Care & Research in October 2016.²

The authors compared 2 patient cohorts drawn from multicenter studies of patients with active RA: The discovery cohort of 700 patients had stable disease activity and treatment with the tumor necrosis factor inhibitor (TNFi) adalimumab, while the treatment cohort consisted of 2,788 patients initiating treatment with adalimumab. The 2 cohorts had similar demographic characteristics.

 

The 1-sided critical difference (d_crit value) was used to establish the PRO thresholds for individual response. The DAS28 was used to assess disease activity, and the Funktionsfragebogen Hannover (FFbH) patient questionnaire was used to assess patient function.

The FFbH is similar to the Health Assessment Questionnaire Disability Index, and the score is based on a scale of 0 to 100 and reflects the patient’s percentage of remaining function.

Additional PROs of pain and fatigue were measured via patients’ indication of status based on a scale of 0 (best possible status) to 10 (worst possible status). 

The results show that all measures of disease activity had high long-term retest reliability (>.75) in the discovery cohort. The authors determined that a a 3 point reduction or more would be required for a therapeutic response in pain, while a 4-point decrease or more would be needed for a therapeutic response in fatigue, and a response in function per the FFbH would require an increase of at least 16 points. Therapeutic response in disease activity was reflected by a DAS28- d_crit value of at least 1.8. 

The 3 PROs improved in 22.7% of all participants, while 22.8% of patients showed no significant PRO improvement. Of the patients who did not reach the minimum DAS28- d_crit response after 12 months, 59.1% showed no significant PRO responses, and only 4.4% patients within this subgroup improved in all 3 PROs.

After 12 months of adalimumab therapy, 53.2% of the treatment cohort demonstrated a significant therapeutic response, as indicated bytheir DAS28 score. Of these patients, 68.5% showed a significant improvement in pain, and improvements in fatigue and function occurred in approximately 40% of this subgroup.

The PRO most closely correlated with patient global assessment (PGA) was pain (Pearson’s r =0.79), which aligns with previous findings that pain accounted for 20% of PGA score variance.

These findings suggest that “improved pain management should be explored in patients who report high disease activity despite favorable changes in objective measures,” the authors wrote.