Aggressive, Early Intervention with Disease-Modifying Drugs Improves Outcomes for Psoriatic Arthritis Patients
Embargo expired: 26-Oct-2013 4:30 PM EDT
Source Newsroom: American College of Rheumatology (ACR)
Newswise — SAN DIEGO — People with psoriatic arthritis who receive early, aggressive pharmacologic intervention following a treat-to-target approach show better outcomes than those who receive standard care, according to research presented this week at the American College of Rheumatology Annual Meeting in San Diego.
Psoriatic arthritis is a type of arthritic inflammation that occurs in about 15 percent of patients who have a skin rash called psoriasis. This particular arthritis can affect any joint in the body, and symptoms vary from person to person.
Research has shown that persistent inflammation from psoriatic arthritis can lead to joint damage, and researchers at the University of Leeds in the United Kingdom investigated the differences in outcome measurements among two groups of psoriatic arthritis patients. The first group was treated according to a tight control approach, following specific guidelines on use of disease-modifying antirheumatic drugs (called DMARDs) to reach set targets in disease-related measurements. The second group was treated with a standard care approach.
The researchers’ overarching goal was “to replicate similar findings in other inflammatory arthropathies, notably rheumatoid arthritis, where a treat-to-target approach is known to favorably influence long-term outcomes for these patients,” says Philip Helliwell, MD; senior lecturer in rheumatology; Leeds Institute of Rheumatic and Musculoskeletal Medicine; and an investigator in the study.
Using data from eight medical treatment centers in the UK from 2008 to 2012, the researchers identified 206 people with psoriatic arthritis and tracked their progress for 48 weeks according to their treatment protocol. The patients in the tight control group were treated with escalating therapy if they did not meet minimal disease activity criteria at set time intervals. These patients were started on the DMARD methotrexate with rapid escalation to a dose of 25mg after six weeks if they tolerated the drug. After 12 weeks, if their disease was not controlled according to the criteria, these patients received a more powerful combination of DMARDs.
After another 12 weeks, if these patients had three or more tender or swollen joints, they were given anti-tumor necrosis factor (Anti-TNF) therapy. If they had less than three tender or swollen joints, but still did not meet the minimal disease activity criteria, they were given methotrexate and an alternative DMARD in combination. The standard treatment group was treated with DMARDS, but with no set time limits for drug therapy escalation or measurements to reach.
The researchers measured the outcomes of the two groups of patients according to the ACR20, ACR50 and ACR70 criteria for disease activity (essentially representing 20, 50, and 70 percent improvement). In the tight control group, 55 percent achieved ACR20, 44 percent achieved ACR50 and 33 percent achieved ACR70. In the standard care group, 37 percent achieved ACR20, 21 percent achieved ACR50 and 15 percent achieved ACR70.
These significant differences show that an aggressive, targeted approach to treating psoriatic arthritis greatly improves disease-activity outcomes for patients with psoriatic arthritis, the researchers concluded. “For the first time, it has been shown that aggressive treatment of inflammation in psoriatic arthritis gives better outcomes,” explains Dr. Helliwell. “Further, the target used in the study – minimal disease activity – assesses a wide spectrum of disease features, including skin and enthesitis, and not just the articular aspects of this complex disease. Patients with this disorder have to endure several different disease manifestations. This study has shown that appropriate targeted therapy can be effective across all these aspects, an important finding for the person with this disorder.”
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 http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official hashtag: #ACR13
Editor’s Notes: Dr. Coates will present this research during the ACR Annual Meeting at the San Diego Convention Center at 2:30 PM on Sunday, October 27 in Room 30 A. Dr. Helliwell will be available for media questions and briefing at 8:30 AM on Monday, October 28 in the on-site press conference room, Room 27 AB.
This study was funded by Arthritis Research UK.
Abstract Number: 814
Results Of a Randomised Controlled Trial Comparing Tight Control Of Early Psoriatic Arthritis (TICOPA) With Standard Care: Tight Control Improves Outcome
Laura C. Coates1, Anna R. Moverley1, Lucy McParland2, Sarah Brown2, Howard Collier2, Jennifer Law2, Sarah R. Brown2, Neil Corrigan2, Nuria Navarro-Coy2, Paul Emery3, Philip G. Conaghan1 and Philip S. Helliwell1, 1NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, United Kingdom, 2Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom, 3Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
Background/Purpose: The aim of this study was to assess the impact of tight control of early psoriatic arthritis (PsA) in a randomised-controlled trial (RCT) using a treat-to-target approach.
Methods: In this UK multicentre, open-label RCT, 206 patients with early DMARD naive PsA (<24 months symptom duration) were randomised 1:1 to receive either tight control (TC) (4 weekly review) or standard care (StdC) (12 weekly review) for 48 weeks. Patients assigned to the TC group followed a strict treatment protocol with escalation of therapy if minimal disease activity (MDA) criteria1were not met. All patients in the TC arm were started on methotrexate with rapid escalation to 25mg after 6 weeks if tolerated. After 12 weeks of therapy, patients were escalated to combination DMARDs if they had not achieved MDA. After a further 12 weeks, patients were either escalated to anti-TNF therapy if they had ≥3 tender and swollen joints (as per UK NICE guidelines) or to an alternative DMARD in combination with methotrexate if they were not in MDA but had <3 active joints. Patients assigned to the StdC group were treated by a rheumatologist with no set protocol and no limitations.
The primary outcome was ACR20 response at 48 weeks. Key secondary outcomes included ACR50 and 70, and PASI75 at 48 weeks. Treatment arms were compared using multivariate logistic regression adjusting for arthritis classification and centre. Missing ACR response component data was imputed using multiple imputation for the intention to treat (ITT) population.
Results:206 patients were recruited from 8 UK centres from 2008-2012 with 101 randomised to TC and 105 to StdC. By week 48, 12 patients had withdrawn (5 TC, 7 StdC) and 12 lost to follow-up (6 TC, 6 StdC). Patients had a median age of 45 (range: 18-80), 52% were male and 71% presented with polyarthritis; these characteristics were similar across treatment arms. In the ITT population, there was significant evidence that the odds of achieving ACR20 at 48 weeks were greater in the TC arm compared to the StdC arm (odds ratio (OR): 1.91, 95% CI: 1.03, 3.55, p=0.0392). The odds of achieving ACR50 (OR: 2.36, 95% CI: 1.25, 4.47, p=0.0081) and ACR70 (OR: 2.64, 95% CI: 1.32, 5.26, p=0.0058) were also greater in the TC arm compared to the StdC arm. Results for patients with non-missing data are displayed below.
The most commonly reported adverse events (AEs) were nausea, liver function test abnormalities and infections (e.g. common cold). AEs were reported in 88% of patients, (97% TC vs 80% StdC). 33 serious AEs (SAEs) (25 TC, 8 StdC) were reported across 20 patients (14 TC, 6 StdC) during the course of the study. There were no deaths or unexpected SAEs.
Conclusion: Tight control of PsA disease activity using a treat-to-target approach significantly improves joint and skin outcomes for newly diagnosed PsA patients with no unexpected SAEs seen.
This study was funded by Arthritis Research UK and Pfizer.
1. Coates et al, Arthritis and Rheum 2010
Disclosures: L. C. Coates, None. A. R. Moverley, None. L. McParland, None. S. Brown, None. H. Collier, None. J. Law, None. S. R. Brown, None. N. Corrigan, None. N. Navarro-Coy, None. P. Emery, None. P. G. Conaghan, Pfizer Inc, Janssen Pharmaceutica Product, L.P., 5, Bristol-Myers Squibb, Pfizer Inc, 8 P. S. Helliwell, Pfizer Inc, 5