RA: Effect of 'Complete Disease Control' on Pain, Function

Janis C. Kelly

September 03, 2014

A retrospective analysis of pooled data from 3 randomized trials of adalimumab plus methotrexate for treatment of rheumatoid arthritis (RA) showed that patients who achieved "complete disease control" (CDC) at week 26 had better pain, fatigue, and health status outcomes than patients who did not reach CDC, according to an industry-funded report published online August 19 in the Annals of the Rheumatic Diseases.

However, the 200 patients who achieved CDC were also younger and had lower disease activity, better function, less pain, less radiographic damage, and less fatigue at baseline than the 1267 patients who did not achieve CDC, Paul Emery, MD, and colleagues report. Dr. Emery is professor of rheumatology at the University of Leeds, United Kingdom.

Rheumatologist Susanna M. Proudman, MD, who was not involved in the study, told Medscape Medical News, "The concept of CDC is more stringent than just disease activity, but combining the components probably identifies a similar group of patients to just [28-joint Disease Activity Score (DAS28)] lower than 2.6 alone. I suspect there is considerable redundancy amongst the 3 components (ie, that most of the DAS28 <2.6 patients also had no radiographic progression and good function). The total number of patients who had DAS28 lower than 2.6, irrespective of the other 2 parameters, was 380 vs 200 with CDC. [The authors suggest] there was no significant difference between these 2 groups except in [Short Form 36] physical function. The authors have not presented a comparison of the work data for these 2 groups. In that sense, CDC moves the goalposts closer to complete remission, but only marginally." Dr. Proudman is senior consultant in rheumatology at Royal Adelaide Hospital in Australia.

The analysis, supported by AbbVie (which also funded the 3 clinical trials involved), defined CDC as DAS28 using C-reactive protein levels lower than 2.6, Health Assessment Questionnaire score lower than 0.5, and change in radiographic progression from baseline in modified Total Sharp Score (mTSS) of 0.5 or lower. The authors pooled data from the 3 randomized controlled trials in RA: the DE019 trial of patients with disease duration of at least 3 years and moderately to severely active RA despite at least 3 months of methotrexate; the Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis (PREMIER) trial of methotrexate-naive patients with disease duration less than 3 years; and the Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) trial of patients with early RA, which included patients who failed to achieve stable low disease activity with methotrexate.

The authors compared patients who reached the 3 criteria for complete disease control with those who did not with regard to work-related outcomes, using data from the Patient Health Economic Questionnaire, the Work Productivity and Activity Impairment, or the RA-Work Instability Scale. They analyzed health-related quality of life using data from the Short Form 36 health survey physical and mental component scores. They used visual analog scale data to measure pain and data from the Functional Assessment of Chronic Illness Therapy-Fatigue to measure fatigue.

At week 26, for patients who achieved CDC vs those who did not, visual analog scale-pain scores had improved by 46.9 vs 26.9 (P < .0001), Functional Assessment of Chronic Illness Therapy-Fatigue had improved by 13.3 vs 7.5 (P < .0001), Short Form 36 physical function had improved by 19.7 vs 8.9 (P < .0001), and Short Form 36 mental function had improved by 8.1 vs 5.0 (P = .0004). Work-related outcomes were also better in CDC achievers than in nonachievers, and American College of Rheumatology/European League Against Rheumatism remission rates were 65% vs 29%.

Dr. Proudman commented, "The patients with CDC had earlier disease, which is presumably why they responded better. They also seemed to have less active disease by the various parameters listed, so they didn't have as far to go to achieve CDC. Some of the parameters are also associated with better prognosis, like lower mTSS and [Health Assessment Questionnaire disability index], although the mTSS would reflect earlier disease too. These patients would not be expected to have as much progression in mTSS or have such high [Health Assessment Questionnaire disability index scores] later in the studies. But the conclusion was that they had larger improvements in other parameters such as fatigue and [quality of life,] despite starting from a better position, so these results are consistent with expectation that some of these factors are associated with better [quality of life] and work outcomes."

The authors write, "Results were consistent at week 52 and among methotrexate-naive patients with early RA, methotrexate-experienced patients with late-stage RA and patients with inadequate response to methotrexate.... These results demonstrate that the joint achievement of all CDC components provides meaningful benefits to patients."

With regard to CDC as a treatment goal in the clinical setting, Dr. Proudman said, "The question is a philosophical one, as there is a difference between the target for use in a treat-to-target strategy and the goal, such as [American College of Rheumatology/European League Against Rheumatism] remission. DAS28 is a reasonable target and, if used in a [treat-to-target] strategy, will increase the likelihood of reaching the goal of therapy. CDC is probably still not the goal (but is currently more achievable than [American College of Rheumatology/European League Against Rheumatism] remission), and it could be a good target. It is not so feasible as DAS28 or DAS28 combined with [Health Assessment Questionnaire disability index] because it requires radiographic scoring, which is only done annually in most studies and requires special expertise (and a serious commitment!). But maybe an alternative radiographic outcome that can be used more frequently, such as ultrasound or [magnetic resonance imaging] might replace mTSS eventually. This is still quite a way off due to the limitations of the current imaging modalities."

The authors did not respond to Medscape Medical News requests for comment.

AbbVie sponsored the studies and participated in study design, data collection, analysis and interpretation, and writing, reviewing, and approval of the final version. Dr. Emery has received grants or research support from AbbVie, Pfizer, Novartis, BMS, and Roche and has served as consultant for AbbVie, Pfizer, MSD, UCB, Roche, Novartis, and BMS. One coauthor has received grants or research support from AbbVie, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB and has served as consultant for: AbbVie, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB. Three other coauthors are employed by and owns shares in AbbVie. Dr. Proudman has disclosed no relevant financial relationships.

Ann Rheum Dis. Published online August 19, 2014. Full text


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