Newswise — BOSTON — Carefully employing a TNF inhibitor dose-reduction strategy can be just as effective at safely treating RA patients as regular dosing methods, while also saving approximately $7,500 per patient annually. This was shown by an 18-month study in 180 RA patients, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in Boston.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

TNF inhibitors like adalimumab (Humira®) or etanercept (Enbrel®) have proven to be effective in RA treatment. However, these drugs may have side effects and are costly, making dose reduction, or discontinuation whenever possible, an attractive option. In a study called DRESS, or Dose Reduction Strategies of Subcutaneous TNF inhibitors, researchers in the Netherlands studied 180 RA patients who had low disease activity and were using either adalimumab or etanercept. The study’s primary goal was to assess whether a strategy including carefully reducing the dose until stopping it, and increasing treatment again when the RA became more active, produces results that are just as good (or non-inferior) as continuing the regular dosing of TNF inhibitors.

“If this approach to individualized dose optimization could be proven to be as effective and safe as regular continuation of the drug, this would have large impact on adverse drug reactions and costs in the millions of patients currently using these drugs,” said Noortje van Herwaarden, MD, of Sint Maartenskliniek in the Netherlands and a lead author on the study.

In the study, the patients were randomized (two to one) to either a dose-reduction strategy or usual care, both in tight control settings. The dose-reduction strategy consisted of stepwise increasing the interval between injections every three months until the patient flared or the drug was discontinued. If a patient had a flare, TNF inhibitors were either restarted or escalated, and no further dose optimization attempts were made. A flare was defined as a DAS28-CRP (a measure for disease activity) increase >1.2, or DAS28-CRP increase >0.6 and current DAS28-CRP ≥3.2, compared to baseline. A persistent flare (the primary outcome) was defined as a flare lasting 12 weeks or more.

During the 18 months of follow-up, data were collected on DAS28-CRP scores, physical function, health related quality of life, RA medication use and costs (including work loss, outpatient visits and travel costs). The primary outcome was the difference in proportions of patients with persistent flare between the two groups, with a difference of less than 20 per cent defined as non-inferiority.

In the dose reduction group, the researchers found that TNF inhibitors could successfully be stopped in 20 percent of the patients. They also found that the interval could be successfully increased in 43 percent of the patients. In 37 percent of the patients, no dose reduction was possible. Incidence and nature of serious adverse events were similar between groups. Costs were significantly lower in the dose-reduction group (mean difference per patient was estimated at €9,000, or $11,480, for the 18-month period).

The study’s authors concluded that a simple, tight control, TNF inhibitor dose-reduction strategy is non-inferior to usual care in maintaining disease control, function and quality of life and radiological disease control in RA patients with low disease activity. This strategy may help reduce health-care costs in this population.

“The results from the DRESS study can have tremendous impact on optimizing RA TNF inhibitor treatment, as it has now been demonstrated that the same treatment results can be obtained with nearly 50 percent reduction in medication exposure and costs. As the yearly revenues for adalimumab and etanercept alone (not taking into account the other biologicals used in rheumatic diseases) exceeds $20 billion, and is still growing, implementation of the DRESS findings could result in improved cost effectiveness of the use of these biologics,” said Dr. van Herwaarden.

###

The American College of Rheumatology is an international professional medical society that represents more than 9,500 rheumatologists and rheumatology health professionals around the world. Its mission is to Advance Rheumatology! The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official #ACR14 hashtag.

Paper Number: 1843

Randomised Controlled Non-Inferiority Study of Dose Reduction and Withdrawal of Adalimumab and Etanercept in Rheumatoid Arthritis

Noortje van Herwaarden1, Aatke van der Maas1, Michiel Minten1, Frank H.J. van den Hoogen2, Ronald F. van Vollenhoven3, Johannes W.J. Bijlsma4, Bart van den Bemt1 and Alfons A. den Broeder1, 1Sint Maartenskliniek, Nijmegen, Netherlands, 2Rheumatology Centre Sint Maartenskliniek and Radboud university medical center, Ubbergen (Nijmegen), Netherlands, 3Unit for clinical therapy research (ClinTrid), Karolinska Institute, Stockholm, Sweden, 4University Medical Center Utrecht, Utrecht, Netherlands

Background/Purpose TNF inhibitors (TNFi) have proven to be effective in the treatment of rheumatoid arthritis (RA). They are however associated with side effects and high costs, making dose reduction or discontinuation an attractive option. The primary aim of this study (DRESS) was to assess non-inferiority with regard to persistent disease worsening (flare) between a TNFi dose reduction strategy and usual care in daily clinical practice. Methods Patients with RA and low disease activity using adalimumab or etanercept were randomised (2:1) to a dose reduction strategy or usual care, both in tight control setting. The TNFi dose reduction strategy consisted of stepwise increasing the interval between injections every 3 months until flare or discontinuation.1 In case of flare, the TNFi was restarted or escalated. A flare was defined as DAS28-CRP increase >1.2 or DAS28-CRP increase >0.6 and current DAS28-CRP ≥3.2, compared to baseline DAS28-CRP.2 A persistent flare was defined as a flare duration ≥ 12 weeks. During 18 months follow up, data were collected on DAS28-CRP, HAQDI, EQ-5D, RA medication use, and costs. The primary outcome was the difference in proportions of patients with persistent flare between the two groups compared against a non-inferiority (NI) margin of 20%. Results 180 patients were included (table 1). Cumulative incidence of persistent DAS28-CRP flare was not significantly higher in the dose reduction group compared to the usual care group, 10% versus 12% of patients respectively (difference 2%, 95% CI -10 to 12), the upper limit of the 95% CI being clearly below the NI margin. Mean DAS28-CRP remained low, with only at 9 months follow up a significant, but small, difference between groups (figure 1A). HAQ scores remained stable in both groups (figure 1B) as did quality of life (figure 1C). In the dose reduction group, the TNFi could successfully be stopped at 18 months in 20% (95% CI 13 to 28) of patients, the interval successfully increased in 43% (95% CI 34 to 53) and in 37% (95% CI 28 to 46) of patients no dose reduction was possible. Incidence and nature of serious adverse events were similar between groups. Costs were significantly lower in the dose reduction group (mean difference per patient €9k).

Conclusion A simple tight control TNFi dose reduction strategy has been shown to be non-inferior to usual care in maintaining disease control, function and quality of life, while reducing exposition to TNFi and costs. References1: den Broeder et al. BMC Musculoskelet Disord. 2013 24;14:299 2: van der Maas et al. Ann Rheum Dis. 2013;72(11):1800-5.

Disclosures: N. van Herwaarden, None.A. van der Maas, Roche, MSD, 9 M. Minten, None.F.H.J. van den Hoogen, None.R.F. van Vollenhoven, Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB, 2, Abbott, BMS, GSK, MSD, Pfizer, Roche, UCB, 5 J.W.J. Bijlsma, AbbVie, Roche, Pfizer, MSD, UCB, BMS, 2, AbbVie, Roche, Pfizer, MSD, UCB, BMS, Jansen, 5 B. van den Bemt, Roche Pharmaceuticals, Pfizer, 2, Roche, Pfizer, MSD Abbvie, 5 A. A. den Broeder, None.

Meeting Link: American College of Rheumatology Annual Meeting

MEDIA CONTACT
Register for reporter access to contact details
CITATIONS

American College of Rheumatology Annual Meeting