Region: RA Revamp

Base article: Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263-269. doi:10.1016/S0140-6736(04)16676-2. PMID 15262104

Authors: Angus B Worthing MD, attending, Arthritis & Rheumatism Associates, PC, Washington DC; Justin Peng MD, attending, Arthritis & Rheumatism Associates, PC, Washington DC; Dan El Bogdadi MD, attending, Arthritis & Rheumatism Associates, PC, Rockville, MD

Team Overview

When this team started playing, it was known that reducing rheumatoid arthritis activity correlated with less joint damage, and early combination oral DMARDs were starting to outperform monotherapy.1,2,3,4,5 Targeted biologic therapy would become available after TICORA was already in process. Our game was entering an exciting era with promising new tools, but a winning formula for treating RA had not yet emerged.

TICORA provided that formula. It was the first blinded study to unveil what would become a standard player in any lineup: the all-star power-forward of an intensive, step-up, treat-to-target strategy in early RA. The intervention strategy included initial sulfasalazine, followed by addition and titration of methotrexate and hydroxychloroquine. At monthly evaluations, oral DMARDs were escalated with intra-articular and/or intramuscular glucocorticoids unless disease activity was low, patients declined or if contraindicated by drug toxicity. Clinical and radiographic evaluators were blinded. At the final buzzer, the box score showed this treat-to-target (T2T) approach outperformed routine care in all relevant stats.

Impact on Rheumatology

It’s hard to overstate TICORA’s effect on the game. As the first truly unbiased T2T trial design in rheumatology (credit an assist to its open-label predecessor FIN-RACo), TICORA helped power a fast-break of clinical trials with combinations and biologics. Research teams would emulate TICORA’s winning formula to test step-up, combination, and biologic treatment strategies using the same blinded, treat-to-target fashion.6,7

T2T is now the key backbone of treatment strategy in major rheumatoid arthritis guidelines.8,9 It has been drafted for use in ankylosing spondylitis, psoriatic arthritis, SLE, gout, and even fibromyalgia.10,11,12,13 And although TICORA’s monthly visit intensity lost popularity, it drove higher remission rates compared to other T2T trials.

As rheumatologists began using T2T in practice, it not only improved patient outcomes but also revolutionized the clinic itself. Rheumatologists in the Mid-Atlantic US, for example, developed a clinical pathway to treat RA which guaranteed access to biologics for patients with active disease. When Medicare’s Quality Payment Program requested innovative Alternate Payment Model (APM) proposals to increase quality and reduce cost in the Medicare system, ACR incorporated T2T into its Alternative Payment Model of RA. 14 And ACR highlighted the Mid-Atlantic T2T pathway in the 2022 Innovation in Clinical Care Award given to our partner Dr. Herb Baraf.15 Therefore, TICORA was not only the original treat-to-target study in rheumatoid arthritis, but also provided a foundation for comparative clinical trials and treatment for RA and many other rheumatologic disease.

Chances in the Tournament

The TICORA Trial squad expects to make a deep run in the RheumMadness 2023 tournament. TICORA tips off against the BeST Trial, which provided novel data about early RA treatment using TICORA’s T2T game plan to compare early step-up combination treatment to 3 other strategies. But BeST has become less relevant now that those strategies – high-dose glucocorticoids, sequential monotherapy, and initial combination TNF plus methotrexate have generally moved to the back of the guideline playbook.16 TICORA Trial’s use of strong scoring fundamentals could put BeST Trial on the defensive. 2nd round action against TEAR Triple Rx and a birth into the Interleukin 8 will have the Blue Ribbon Panel pick between TICORA’s fundamental X’s and O’s, and trick-shot triple therapy and TNFs. The BRP would be wise to heed hoops legend Larry Bird, who said, “First, master the fundamentals.” And how fitting would it be for the archetypal TICORA to face an Origin Story Bracket team in the Championship?

Whatever happens, this future Hall of Famer will be always be a slam dunk for rheumatology.

Next scouting report: Clonal Selection

Back to the full list of scouting reports.

See the Q&A on theMednet.org for the RA Revamp Region: What target do you utilize in clinical practice for defining disease remission in RA?


  1. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263-269. doi:10.1016/S0140-6736(04)16676-2
  2. Plant MJ, Williams AL, O’Sullivan MM, et al. Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis. Arthritis Rheum 2000; 43(7): 1473–77. doi: 10.1002/1529-0131(200007)43:7<1473::AID-ANR9>3.0.CO;2-N. PMID: 10902748
  3. Haagsma CJ, van Riel PL, de Jong AJ, et al. Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol. 1997;36(10):1082-8. doi: 10.1093/rheumatology/36.10.1082. PMID: 9374925.
  4. Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997;350(9074):309-18. doi: 10.1016/S0140-6736(97)01300-7.
  5. Sokka T, Mäkinen H, Puolakka K, et al. Remission as the treatment goal–the FIN-RACo trial. Clin Exp Rheumatol. 2006;24(6 Suppl 43):S-74-6. PMID: 17083766.
  6. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52(11):3381-90. doi: 10.1002/art.21405. PMID: 16258899.
  7. Moreland, L.W., O’Dell, J.R., Paulus, H.E., et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: The Treatment of Early Aggressive Rheumatoid Arthritis trial. Arthritis Rheum. 2012;64(9): 2824-2835. https://doi.org/10.1002/art.34498
  8. Smolen JS, Aletaha D, Bijlsma JWJ for the T2T Expert Committee, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Annals of the Rheumatic Diseases. 2010;69:631-637. http://dx.doi.org/10.1136/ard.2009.123919
  9. Singh, J.A., Furst, D.E., Bharat, A., et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012;64: 625-639. https://doi.org/10.1002/acr.21641
  10. Smolen JS, Braun J, Dougados M, et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: Recommendations of an international task force. Ann. Rheum. Dis. 2014;73:6–16. doi: 10.1136/annrheumdis-2013-203419
  11. van Vollenhoven RF, Mosca M, Bertsias G et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis. 2014;73(6):958-67. doi: 10.1136/annrheumdis-2013-205139. Epub 2014 Apr 16. PMID: 24739325.
  12. Stamp, LK, Frampton C, Morillon MB, et al. Association between serum urate and flares in people with gout and evidence for surrogate status: a secondary analysis of two randomised controlled trials. The Lancet Rheumatology. 2022;4(1) e53–e60. https://doi.org/10.1016/S2665-9913(21)00319-2.
  13. Häuser, W, Clauw, DJ, Fitzcharles, MA. Treat-to-Target Strategy for Fibromyalgia: Opening the Dialogue. Arthritis Care Res. 2017;69: 462-466. https://doi.org/10.1002/acr.22970
  14. Nierengarten, MB. The ACR is exploring a rheumatology-specific APM. The Rheumatologist. 2017 at https://www.the-rheumatologist.org/article/acr-exploring-rheumatology-specific-apm/?singlepage=1 accessed January 11, 2023
  15. Fusillo, P. The 2022 ACR awards of distinction. The Rheumatologist. 2022 at https://www.the-rheumatologist.org/article/the-2022-acr-awards-of-distinction/?singlepage=1 accessed January 11, 2023
  16. Fraenkel, L, Bathon, JM, England, BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021;73: 924-939. https://doi.org/10.1002/acr.24596

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