Research Finds High Percentage of Rheumatoid Arthritis Patients Discontinue Triple Therapy After Two Years

by Kathy Jones on Oct 28 2013 8:24 PM

 Research Finds High Percentage of Rheumatoid Arthritis Patients Discontinue Triple Therapy After Two Years
Research presented at the American College of Rheumatology Annual Meeting in San Diego says that a high percentage of rheumatoid arthritis patients discontinue triple therapy, a combination of disease-modifying antirheumatic drugs, after one to two years.
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.

Researchers used data from the National Data Bank for Rheumatic Diseases, a depository of data on rheumatic disease patients in the United States, to examine the discontinuation rates of triple therapy among RA patients. Drug discontinuation rates are an indicator of effectiveness and may be used in health economic models to determine cost-effectiveness. Triple therapy for RA includes methotrexate, sulfasalazine and hydroxychloroquine. Data on 10,156 RA patients from 1998 to 2012 were analyzed to determine what percentage of patients discontinued triple therapy, and how long they took the combination of drugs before discontinuing or adding a biologic drug.

"The 2012 ACR RA guidelines recommend that physicians add either another DMARD (or two) or an anti- TNF biologic if initial methotrexate monotherapy is not satisfactory. There have been many studies investigating the comparative effectiveness via discontinuation rates of recent treatments for RA, but little to none looking at triple or combination DMARD therapy," explains Kaleb Michaud, PhD; assistant professor, University of Nebraska Medical Center & co-director, National Data Bank for Rheumatic Diseases; and lead investigator in the study.

"Recent results of the TEAR and RACAT clinical trials demonstrate the comparable efficacy [effectiveness] of triple therapy with anti-TNF and emphasize the importance of understanding how this treatment has been used in the real-world. It is possible that these trials may result in increased usage of triple therapy."

No data was available on when triple therapy was first prescribed for these patients, so the researchers used two definitions of discontinuation. The first definition was when patients discontinued taking all three drugs. The second definition was when patients stopped taking any combination of the drugs or when they added a different drug, including biologics. Of all the patients, 388 initiated triple therapy at some point. Of those, 304 - or 78.4 percent - discontinued triple therapy at some point according to the second definition, with 121 immediately switching to or adding another DMARD, and 183 dropping one or two of the drugs in the combination. A total of 216 - or 55.7 percent - of the triple therapy patients discontinued the combination according to the second definition. The annual discontinuation rate of triple therapy by both definitions was 408 cases per 1000 person-years by the first definition and 235 cases per 1000 person years by the second definition. Median time on triple therapy was 14 months, and doubled to 28 months when using the second definition. At two years, discontinuations were at 39.1 percent and 53.4 percent by the first and second definitions respectively.

After discontinuation of triple therapy according to either definition, 59.3 percent tended to switch to or add another DMARD, while 41.2 percent added a biologic drug.

"With emphasis on reaching a targeted low-disease activity state, physicians have many drugs to choose from for treating RA patients including triple therapy. These results show that a) triple therapy has been used in a relatively small percentage of RA patients since 1998 (~1% of RA patients in the NDB), and b) patients are not on triple therapy for very long before they switch to something else," said Dr. Michaud. "It is likely that physicians add either sulfasalazine or hydroxychloroquine one at a time to see if each drug works and is tolerated before adding the next drug. Patients prefer fewer drugs and physicians are being more responsive, so if two are working, they are less likely to add a third, and if three are working, they are more likely to see if dropping one or two would still keep their RA controlled. Triple therapy is not marketed to patients nor is it taken as a single pill; this makes interpreting these higher discontinuation rates more difficult."

Patients should talk to their rheumatologists to determine their best course of treatment.

Dr. Michaud is supported by a 2012 Investigator Award from the Rheumatology Research Foundation. The American College of Rheumatology is an international professional medical society that represents more than 9,000 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 or join the conversation on Twitter by using the official hashtag: #ACR13

Editor''s Notes: Dr. Pedro will present this study during the ACR Annual Meeting at the San Diego Convention Center from 9:00 - 11:00 AM in Exhibit Hall B2 C-D on Tuesday, October 29. Dr. Michaud will be available for media questions and briefing at 8:30 AM Tuesday, October 29 in the on-site press conference room, 27 AB.

Abstract Number: 1055

Discontinuation Rates In Patients With RA Of Triple Disease Modifying Antirheumatic Therapy

Sofia Pedro1, Frederick Wolfe1, Hawre Jalal2 and Kaleb Michaud3, 1National Data Bank for Rheumatic Diseases, Wichita, KS, 2University of Minnesota, Minneapolis, MN, 3National Data Bank for Rheumatic Diseases & University of Nebraska Medical Center, Omaha, NE

Background/Purpose: Drug discontinuation rates are measures of effectiveness and are needed in health economic models. While a recent RCT demonstrated statistical equivalence of efficacy with etanercept [1], little is known regarding the real-world use and discontinuation rates of triple therapy, which includes methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ).

Methods: We evaluated the treatment discontinuation rates of triple therapy in rheumatoid arthritis using a large observational cohort, the National Data Bank for Rheumatic diseases. We initially defined discontinuation as when all 3 DMARDs (MTX, SSZ & HCQ) were not taken (First). Since we cannot verify if triple therapy was purposely prescribed, our second discontinuation definition occurred when the patient was no longer on any combination of the 3 DMARDs or if they added a biologic (Second). In both cases missing data between periods on triple therapy were assumed to remain on treatment. Kaplan- Meier survivor functions were used to analyze discontinuation rates.

Results: From 10,156 patients on biologics and DMARDs, 388 (3.8%) initiated triple therapy at some point between 1998-2012. From these 304 (78.4%) discontinued triple therapy according to our first definition with 121 (39.8%) immediately switching to or adding another DMARD while 183 (60.2%) dropped one or two of the 3 drugs. A total of 216 (55.7%) discontinued according to our second definition. The discontinuation rate of triple therapy by our two definitions were 40.8% (First) and 23.5% (Second) per year (See Table). The median survival on triple therapy was 14 months (IQR 6-45 months), and doubled to 28 months (IQR: 10-112 months) when using the second definition. At 24 months, the discontinuation rates were: 39.1% (95% CI 33.9%- 44.2%) and 53.4% (95% CI 48.2%-59.0%), for first and second definitions respectively. After triple therapy, patients tended to switch/add more DMARDs afterwards (59.3%) than biologics (41.2%).

Conclusion: This is the first study to provide discontinuation rates of triple therapy using community experience in the biologic era. Overall discontinuation rates were high and patients tended to switch between several combinations of MTX, SSZ, and HCQ. Future work is needed to identify rates of prescription and patient/physician preferences for triple therapy.

[1] O''Dell JR et al. Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med.2013

Disclosures: S. Pedro, Natinal DataBank for Rheumatic Disease, 3
F. Wolfe, None
H. Jalal, None
K. Michaud, University of Nebraska Medical Center, 3, National Data Bank for Rheumatic Diseases, 3