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4 Articles in this Series
Introduction
Explaining the Transition to Chronic Pain in Knee Osteoarthritis
NSAID/TNF Inhibitor Combination May Slow Spine Damage in AS
PROMIS May Deliver Meaningful Interpretation of Pain Relief
To Taper or Not To Taper DMARDS When RA Activity is Low?

To Taper or Not To Taper DMARDS When RA Activity is Low?

With Paul Emery, MD, and Arthur Kavanaugh, MD, and commentary by Jasvinder Singh, MD, MPH

 

Sorting out the research and patient experiences, experts explore the pros, cons of tapering DMARDs  

When rheumatoid arthritis disease activity is low, physicians face a challenging decision: to taper the biologic disease-modifying antirheumatic drugs (DMARDs) or to maintain therapy. This topic made for a lively session between Paul Emery, MD, FRCP, and Arthur Kavanaugh, MD,1 at the 2016 American College of Rheumatology/Association of Rheumatology Health Professionals annual meeting in Washington, DC.

"In the treatment guidelines,2 the recommendation is not to taper'' if disease activity is low. In remission, the guidelines state, tapering is a possibility, but the guidelines recommend against discontinuing all RA therapies,” Jasvinder Singh, MD, MPH, lead author of the current American College of Rheumatology treatment guidelines, and session moderator, told Practical Pain Management.

Even so, patients often prefer the least amount of medication, so there are pros and cons to consider with regard to tapering, Dr. Singh said.

Advocating in Favor of Tapering

The biggest take-home, said Paul Emery, MD, FRCP, Arthritis Research UK Professor of Rheumatology and director of the Leeds MSK Biomedical Research Centre at University of Leeds, U.K, is that ''tapering is quite safe in patients who go into remission quickly.''

To predict which patients meet this criteria, imaging and immunologic testing can help, Dr. Emery said. "My view is, analyze the patient in front of you, and if you use all the available technologies, you can be much more accurate in your predictions."

In addition, Dr. Emery indicated several other benefits of tapering for consideration:

  • Cost saving
  • Patient preference for less medication
  • When treatment is individualized, control is easily regained if the dose needs to be boosted

Several safety issues are dose dependent, such as infections and malignancy, according to Dr. Emery. He cited a 2006 study,3 in which researchers conducted a systemic review of rare, harmful effects with anti-tumor necrosis factor antibody (TNFi) therapy, and found a pooled odds ratio for malignancy was 3.3 (95% CI, 1.2-9.1) and for serious infection 2.0 (95% CI, 1.3-3. Making sense of the data is a challenge, Dr. Emery said, and urged physicians to recognize the difference between a dose reduction and a complete discontinuation of the medication, and to look at early versus late remission.

In addition, Dr. Emery offered 2 more points to keep in mind with regard to tapering:

  • Discontinuing therapy when in remission on TNFI is only effective with early remission induction
  • 3 studies may be consulted as a guide to dose reduction in early disease: AGREE,4 PRIZE5 and C-Early6.

In the PRIZE trial, continuing combination therapy at a reduced dose produced better disease control than switching to methotrexate alone or with placebo, if patients had remission while on full dose etanercept plus methotrexate.

Against Tapering Out of Consideration of Sequalae

It is difficult to identify which patients might be suitable candidates for tapering, according to Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California, San Diego, in presenting the argument against tapering.1

''While some patients can do it, others cannot, and their disease flares," Dr. Kavanaugh told Practical Pain Management.

Dr. Kavanaugh raised a few other concerns:

  • Tapering doesn't always work; not all patients can readily achieve the good (remission) levels of disease activity, for example, that they had while on treatment, Dr. Kavanaugh said.
  • Controlling just the RA isn't the only concern, "while we are focused on the articular aspects of disease, RA is a systemic disease, and we must be attentive to the other sequalae of uncontrolled inflammation, such as cardiovascular disease, infections, osteoporosis and so on," Dr. Kavanaugh told Practical Pain Management.

Dr. Kavanaugh also addressed a concern that tapering might be required of rheumatologists solely for financial reasons, and that could put physicians in a tough spot ethically. He referred to a new guideline in the Capital Region of Denmark, requiring that RA patients who were in sustained remission on biological therapy must attempt dose reduction, according to a predefined algorithm. However, at one year, 70% or 101 of 143 patients flared, according to data presented by other researchers at the ACR meeting.7 All patients were then reescalated and regained remission.

Dr. Emery reports providing expert advice to Abbvie, BMS, Gilead, MSD, Novartis, Pfizer, Roche, Samsung, Sandoz, UCB and Lilly.Dr. Kavanaugh reports disclosures for AbbVie, Amgen, Astellas, Astra Zeneca/Medimmune/Ardea, Biogen-Ide, BMS, Celgene, Crescendo/Myriad, Galapagos/Gilead, Genentech/Roche, Janssen, Novartis, Pfizer, Regeneron/Sanofi-Aventis, UCB, ITN, LCTC, LAI, NIH, TREG.

Sources:

1. Kavanaugh, A. and Emery, P. To Taper or Not To Taper? Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity. Lecture at 2016 ACR/AHRP Annual Meeting, November11-15, 2016. Washington, D.C.

2. Signh JA, Saag KG, Bridges L, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.

3. Bongartz T,  Sutton AJSweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.JAMA 2006:295(19):275-2285.

4. Smolen JS, Wollenhaupt J, Gomez-Reino JJ. Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE). Arthritis Res Ther. 2015;17(1):157.

5.  Zhang W, Bansback N, Sun H, Pedersen R, Kotak S, Anis AH. Impact of etanercept tapering on work productivity in patients with early rheumatoid arthritis: results from the PRIZE study. RMD Open. 2016;2(2):e000222.

6.  Emery P, Bingham CO, Burmester GR. Certolizumab pegol in combination with dose-optimized methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomized, double-blind, placebo-controlled phase III study. Ann Rheum Dis. 2016 May 10. [Epub ahead of print]

7. Brahe CH. Dose Reduction or Discontinuation of Biological Therapy in Patients with Rheumatoid Arthritis in Remission—1-Year Results of a Guideline-Directed Longitudinal Cohort Study. Poster presented at 2016 ACR/ARHP Annual Meeting, November 11-15, Washington, D.C.

 

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