Nonsteroidal Anti-inflammatory Drugs vs Cognitive Behavioral Therapy for Arthritis Pain | Geriatrics | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Nonsteroidal Anti-inflammatory Drugs vs Cognitive Behavioral Therapy for Arthritis PainA Randomized Withdrawal Trial

Educational Objective
To evaluate whether discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis (OA).
1 Credit CME
Key Points

Question  Is replacing meloxicam with placebo noninferior to continued meloxicam, and is engaging in a telephone-based cognitive behavioral therapy program noninferior to continuing meloxicam for patients with knee osteoarthritis?

Findings  In this multicenter randomized withdrawal trial, the pain scores of patients randomized to stop meloxicam were inferior at 4 weeks to the pain scores of patients who continued meloxicam; the pain scores of patients who engaged in cognitive behavioral therapy after placebo were also inferior to the pain scores of patients who continued meloxicam. However, the pain score differences between the 2 groups were small (less than the minimal clinically important difference), and there were no statistically significant differences in patients’ reported global impression of change or function.

Meaning  Among patients with knee osteoarthritis, placebo and cognitive behavioral therapy (after placebo) are inferior to meloxicam.

Abstract

Importance  Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects.

Objective  To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis.

Design, Setting, and Participants  The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis.

Interventions  Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2).

Main Outcomes and Measures  The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks.

Results  A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, –0.2; 95% CI, –0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, –1.4 to 3.2; P = .45) between the 2 groups after 14 weeks.

Conclusions and Relevance  Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants’ global impression of change or function after 14 weeks.

Trial Registration  ClinicalTrials.gov Identifier: NCT01799213

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: May 25, 2020.

Corresponding Author: Liana Fraenkel, MD, MPH, Section of Rheumatology, Yale University School of Medicine, 300 Cedar St, PO Box 208031, TAC Building, Room 525, New Haven, CT 06520 (liana.fraenkel@yale.edu).

Published Online: July 20, 2020. doi:10.1001/jamainternmed.2020.2821

Author Contributions: Drs Fraenkel and Buta had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Fraenkel, Suter, Corn, Kerns, Goulet.

Acquisition, analysis, or interpretation of data: Fraenkel, Buta, Dubreuil, Levy, Najem, Brennan, Corn, Kerns, Goulet.

Drafting of the manuscript: Fraenkel, Buta, Brennan, Goulet.

Critical revision of the manuscript for important intellectual content: Fraenkel, Buta, Suter, Dubreuil, Levy, Najem, Corn, Kerns, Goulet.

Statistical analysis: Buta, Goulet.

Obtained funding: Fraenkel, Kerns, Goulet.

Administrative, technical, or material support: Suter, Levy, Brennan, Corn.

Supervision: Fraenkel, Kerns.

Conflict of Interest Disclosures: Drs Fraenkel and Goulet reported receiving grants from the Veterans Affairs Health Services Research and Development during the conduct of the study. Dr Suter reported other support from Veterans Health Administration during the conduct of the study and other support from the Centers for Medicare & Medicaid Services outside the submitted work. Dr Levy reported receiving salary support from the North Florida/South Georgia Veterans Health System during the conduct of the study. No other disclosures were reported.

Funding/Support: This trial was funded by grant IIR 11-113 from the Veterans Affairs Health Services Research and Development Service.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.

Additional Information: Research resources generated with funds from this grant will be freely distributed, as available, to qualified academic investigators for noncommercial research. Deidentified data will be shared with the research community once the project has been completed and the resulting manuscripts have been accepted for publication. The study protocol and results will be uploaded to Clinical Trials.gov. The proposed research will include data from all enrolled participants. The final data set will be stripped of identifiers prior to release for sharing. Even so, in order to ensure protection of participants, we will make the data and associated documentation available to users only under a data sharing agreement that provides for (1) a commitment to using the data only for research purposes and not to identify any individual participant, (2) a commitment to securing the data using appropriate computer technology, and (3) a commitment to destroying or returning the data after analyses are completed.

References
1.
Neogi  T , Zhang  Y .  Epidemiology of osteoarthritis.   Rheum Dis Clin North Am. 2013;39(1):1-19. doi:10.1016/j.rdc.2012.10.004 PubMedGoogle Scholar
2.
Lee  C , Straus  WL , Balshaw  R , Barlas  S , Vogel  S , Schnitzer  TJ .  A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis.   Arthritis Rheum. 2004;51(5):746-754. doi:10.1002/art.20698 PubMedGoogle Scholar
3.
Jordan  KM , Arden  NK , Doherty  M ,  et al; Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT.  EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT).   Ann Rheum Dis. 2003;62(12):1145-1155. doi:10.1136/ard.2003.011742 PubMedGoogle Scholar
4.
Bjordal  JM , Ljunggren  AE , Klovning  A , Slørdal  L .  Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials.   BMJ. 2004;329(7478):1317. doi:10.1136/bmj.38273.626655.63 PubMedGoogle Scholar
5.
Gregori  D , Giacovelli  G , Minto  C ,  et al.  Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis.   JAMA. 2018;320(24):2564-2579. doi:10.1001/jama.2018.19319 PubMedGoogle Scholar
6.
Meek  IL , Van de Laar  MAFJ , Vonkeman  HE .  Non-steroidal anti-inflammatory drugs: an overview of cardiovascular risks.   Pharmaceuticals (Basel). 2010;3(7):2146-2162. doi:10.3390/ph3072146 PubMedGoogle Scholar
7.
Vonkeman  HE , van de Laar  MA .  Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.   Semin Arthritis Rheum. 2010;39(4):294-312. doi:10.1016/j.semarthrit.2008.08.001 PubMedGoogle Scholar
8.
Beck  AT , Dozois  DJA .  Cognitive therapy: current status and future directions.   Annu Rev Med. 2011;62:397-409. doi:10.1146/annurev-med-052209-100032 PubMedGoogle Scholar
9.
Dixon  KE , Keefe  FJ , Scipio  CD , Perri  LM , Abernethy  AP .  Psychological interventions for arthritis pain management in adults: a meta-analysis.   Health Psychol. 2007;26(3):241-250. doi:10.1037/0278-6133.26.3.241 PubMedGoogle Scholar
10.
Ehde  DM , Dillworth  TM , Turner  JA .  Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research.   Am Psychol. 2014;69(2):153-166. doi:10.1037/a0035747 PubMedGoogle Scholar
11.
Keefe  FJ , Lumley  M , Anderson  T , Lynch  T , Studts  JL , Carson  KL .  Pain and emotion: new research directions.   J Clin Psychol. 2001;57(4):587-607. doi:10.1002/jclp.1030 PubMedGoogle Scholar
12.
Niknejad  B , Bolier  R , Henderson  CR  Jr ,  et al.  Association between psychological interventions and chronic pain outcomes in older adults: a systematic review and meta-analysis.   JAMA Intern Med. 2018;178(6):830-839. doi:10.1001/jamainternmed.2018.0756 PubMedGoogle Scholar
13.
Bernardy  K , Klose  P , Busch  AJ , Choy  EHS , Häuser  W .  Cognitive behavioural therapies for fibromyalgia.   Cochrane Database Syst Rev. 2013;9(9):CD009796.PubMedGoogle Scholar
14.
Eccleston  C , Fisher  E , Craig  L , Duggan  GB , Rosser  BA , Keogh  E .  Psychological therapies (internet-delivered) for the management of chronic pain in adults.   Cochrane Database Syst Rev. 2014;2(2):CD010152. doi:10.1002/14651858.CD010152.pub2 PubMedGoogle Scholar
15.
Goulet  JL , Buta  E , Brennan  M , Heapy  A , Fraenkel  L .  Discontinuing a non-steroidal anti-inflammatory drug (NSAID) in patients with knee osteoarthritis: design and protocol of a placebo-controlled, noninferiority, randomized withdrawal trial.   Contemp Clin Trials. 2018;65:1-7. doi:10.1016/j.cct.2017.11.020 PubMedGoogle Scholar
16.
Zhao  SZ , McMillen  JI , Markenson  JA ,  et al.  Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib.   Pharmacotherapy. 1999;19(11):1269-1278. doi:10.1592/phco.19.16.1269.30879 PubMedGoogle Scholar
17.
Otis  JD .  Managing Chronic Pain: A Cognitive-Behavioral Therapy Approach. Oxford University Press; 2007.
18.
Rogers  JC , Irrgang  JJ .  Measures of adult lower extremity function: The American Academy of Orthopedic Surgeons Lower Limb Questionnaire, The Activities of Daily Living Scale of the Knee Outcome Survey (ADLS), Foot Function Index (FFI), Functional Assessment System (FAS), Harris Hip Score (HHS), Index of Severity for Hip Osteoarthritis (ISH), Index of Severity for Knee Osteoarthritis (ISK), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).   Arthritis Care Res (Hoboken). 2003;49(S5):S67-S84. doi:10.1002/art.11401 Google Scholar
19.
McConnell  S , Kolopack  P , Davis  AM .  The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties.   Arthritis Rheum. 2001;45(5):453-461. doi:10.1002/1529-0131(200110)45:5<453::AID-ART365>3.0.CO;2-W PubMedGoogle Scholar
20.
Strand  V , Kelman  A .  Outcome measures in osteoarthritis: randomized controlled trials.   Curr Rheumatol Rep. 2004;6(1):20-30. doi:10.1007/s11926-004-0080-6 PubMedGoogle Scholar
21.
Angst  F , Aeschlimann  A , Steiner  W , Stucki  G .  Responsiveness of the WOMAC osteoarthritis index as compared with the SF-36 in patients with osteoarthritis of the legs undergoing a comprehensive rehabilitation intervention.   Ann Rheum Dis. 2001;60(9):834-840.PubMedGoogle Scholar
22.
van Buuren  S , Groothuis-Oudshoorn  K .  mice: Multivariate imputation by chained equations in R.   J Stat Softw. 2011;45:1-67. doi:10.18637/jss.v045.i03 Google Scholar
23.
D’Agostino  RB  Sr , Massaro  JM , Sullivan  LM .  Non-inferiority trials: design concepts and issues—the encounters of academic consultants in statistics.   Stat Med. 2003;22(2):169-186. doi:10.1002/sim.1425 PubMedGoogle Scholar
24.
Alderson  P , Chalmers  I .  Survey of claims of no effect in abstracts of Cochrane reviews.   BMJ. 2003;326(7387):475. doi:10.1136/bmj.326.7387.475 PubMedGoogle Scholar
25.
Keefe  FJ , Caldwell  DS , Williams  DA ,  et al.  Pain coping skills training in the management of osteoarthritic knee pain, II: follow-up results.   Behav Ther. 1990;21(4):435-447. doi:10.1016/S0005-7894(05)80357-0 Google Scholar
26.
Kidd  BL , Langford  RM , Wodehouse  T .  Arthritis and pain: current approaches in the treatment of arthritic pain.   Arthritis Res Ther. 2007;9(3):214. doi:10.1186/ar2147 PubMedGoogle Scholar
27.
René  J , Weinberger  M , Mazzuca  SA , Brandt  KD , Katz  BP .  Reduction of joint pain in patients with knee osteoarthritis who have received monthly telephone calls from lay personnel and whose medical treatment regimens have remained stable.   Arthritis Rheum. 1992;35(5):511-515. doi:10.1002/art.1780350504 PubMedGoogle Scholar
28.
Maisiak  R , Austin  J , Heck  L .  Health outcomes of two telephone interventions for patients with rheumatoid arthritis or osteoarthritis.   Arthritis Rheum. 1996;39(8):1391-1399. doi:10.1002/art.1780390818 PubMedGoogle Scholar
29.
Allen  KD , Oddone  EZ , Coffman  CJ ,  et al.  Telephone-based self-management of osteoarthritis: a randomized trial.   Ann Intern Med. 2010;153(9):570-579. doi:10.7326/0003-4819-153-9-201011020-00006 PubMedGoogle Scholar
30.
Baker  K , LaValley  MP , Brown  C , Felson  DT , Ledingham  A , Keysor  JJ .  Efficacy of computer-based telephone counseling on long-term adherence to strength training in elders with knee osteoarthritis: a randomized trial.   Arthritis Care Res (Hoboken). Published online May 10, 2019. doi:10.1002/acr.23921 PubMedGoogle Scholar
31.
Kerns  RD , Burns  JW , Shulman  M ,  et al.  Can we improve cognitive-behavioral therapy for chronic back pain treatment engagement and adherence? a controlled trial of tailored versus standard therapy.   Health Psychol. 2014;33(9):938-947. doi:10.1037/a0034406 PubMedGoogle Scholar
32.
Yocum  D , Fleischmann  R , Dalgin  P , Caldwell  J , Hall  D , Roszko  P ; The Meloxicam Osteoarthritis Investigators.  Safety and efficacy of meloxicam in the treatment of osteoarthritis: a 12-week, double-blind, multiple-dose, placebo-controlled trial.   Arch Intern Med. 2000;160(19):2947-2954. doi:10.1001/archinte.160.19.2947 PubMedGoogle Scholar
33.
Somers  TJ , Blumenthal  JA , Guilak  F ,  et al.  Pain coping skills training and lifestyle behavioral weight management in patients with knee osteoarthritis: a randomized controlled study.   Pain. 2012;153(6):1199-1209. doi:10.1016/j.pain.2012.02.023 PubMedGoogle Scholar
34.
Vitiello  MV , Rybarczyk  B , Von Korff  M , Stepanski  EJ .  Cognitive behavioral therapy for insomnia improves sleep and decreases pain in older adults with co-morbid insomnia and osteoarthritis.   J Clin Sleep Med. 2009;5(4):355-362. doi:10.5664/jcsm.27547 PubMedGoogle Scholar
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close