Clinical trial NCT01106079: TIght COntrol of Psoriatic Arthritis
Official title: A Randomised Controlled Trial to Compare Intensive Management vs Standard Care in Early Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: Early psoriatic arthritis
Tight control
Intensive management
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: Arthritis Research UK
name: Pfizer
First posted: 2010-04-19
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate whether tight control of patients with newly diagnosed psoriatic arthritis (consisting of regular 4 weekly objective assessment of disease activity and protocol-led intensive treatment) can improve outcome as opposed to standard care (usually 3 monthly reviews with no objective outcome measures and no protocol for treatment). The principle hypothesis of this study is that tight control of inflammation in psoriatic arthritis using a treatment protocol and pre-defined objective targets for treatment will lead to an improvement in patients' disease activity and a reduction in radiological joint damage.

Detailed description: The TICOPA trial is designed as a randomised, controlled, parallel group, open label, multi-centre clinical trial of 206 patients with recent onset psoriatic arthritis. Patients will be randomised on a 1:1 basis to receive either standard care (12 weekly review) or tight control (4 weekly review) for a period of 48 weeks. The hypothesis is that tight control of inflammation will lead to a better outcome in terms of joint inflammation, joint damage, pain and quality of life for people with PsA. This imaging undertaken within the study will provide a further measure of joint inflammation and damage and will improve understanding of the relationships between inflammation, damage and bony proliferation in psoriatic arthritis.

Those subjects randomised to the tight control arm will be reviewed every 4 weeks (by the PI at each site or a designated researcher), and will be treated according to a rapidly escalating regime, involving standard DMARDs and biologics. Initial therapy will be with oral methotrexate, increasing in dose rapidly over the first 8 weeks of the study. From the 12 week visit onwards, escalation of therapy in this arm will be performed if subjects do not meet the objective target of Minimal Disease Activity. Initial escalation will be to combination DMARD therapy. If patients in the tight control arm fail to meet the MDA criteria and fulfil the NICE criteria for the use of TNF blockers in psoriatic arthritis at 24 weeks, then they will be offered treatment with these medications. Therapy will continue to be modified throughout the 48 week follow-up until a state of minimal disease activity is reached. The control group will be seen every 12 weeks in a general rheumatology clinic and will receive standard care, involving standard DMARDs and biologics as appropriate. Treatment will be prescribed as felt appropriate by the treating physicians with no set protocol and no restrictions.

All subjects will be treated and followed-up for 48 weeks from randomisation according to their treatment allocation and will have 12 weekly clinical disease assessments throughout this period by a fully trained, blinded assessor. This will include measures of disease activity in all of the five aspects of PsA (joint disease, skin disease, enthesitis, dactylitis and spinal disease).

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of psoriatic arthritis by a consultant Rheumatologist with less than 24 months disease duration.
* Active disease defined by at least one tender or swollen joint or active enthesitis.
* Age ≥18 years at the time of signing the informed consent form and either male or female patients.
* Patient understands the objectives of the study and is able and willing to sign the Informed Consent Form.
* Men and women of child bearing potential (WCBP) must use at least one adequate birth control measure for the duration of the study and should continue such precautions for 6 months after receiving the last dose of protocol treatment.
* Adequate full blood count within 28 days before randomisation:

  * Haemoglobin count \> 8.5 g/dL
  * White blood count (WBC) \> 3.5 x 10\*9/L
  * Absolute neutrophil count (ANC) \> 1.5 x 10\*9/L
  * Platelet count \> 100 x 10\*9/L
* Adequate hepatobiliary function within 28 days before randomisation:

  \*ALT and/or AST levels must be within 3 times the upper limit of normal range (ULN) for the laboratory conducting the test.
* The patient must be able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

* Previous treatment for articular disease with disease modifying drugs (DMARDs) including, but not limited to, methotrexate, sulfasalazine, leflunomide,
* Women who are pregnant, lactating or planning pregnancy within 6 months of their last dose of protocol treatment.
* Use of any investigational agents within 4 weeks or within 5 half-lives of the investigational agent, whichever is longer, prior to randomisation.

Primary outcomes:
measure: Proportion of patients achieving an ACR20 response.
timeFrame: 48 weeks
Secondary outcomes:
measure: Additional clinical efficacy outcomes
timeFrame: 24 weeks
measure: Comparison between intensive management and standard care in terms of Quality of Life (QoL),using PsAQoL
timeFrame: 24 weeks
measure: To compare intensive management with standard care in terms of cost effectiveness
timeFrame: 12 weeks
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: From baseline until 52 weeks
measure: Imaging efficacy: PsAMRIS and ultrasound assessment of disease
timeFrame: 48 weeks
measure: Additional clinical efficacy outcomes
timeFrame: 48 weeks
measure: Comparison between intensive management and standard care in terms of Quality of Life (QoL),using PsAQoL
timeFrame: 48 weeks
measure: To compare intensive management with standard care in terms of cost effectiveness
timeFrame: 24 weeks
measure: To compare intensive management with standard care in terms of cost effectiveness
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
state: West Yorkshire
city: Bradford
country: United Kingdom
facility: St Luke's Hospital
city: York
country: United Kingdom
facility: York District Hospital
Study officials:
affiliation: University of Leeds
name: Philip Helliwell
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coates LC, Mahmood F, Emery P, Conaghan PG, Helliwell PS. The dynamics of response as measured by multiple composite outcome tools in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial. Ann Rheum Dis. 2017 Oct;76(10):1688-1692. doi: 10.1136/annrheumdis-2017-211137. Epub 2017 Jun 12.
citation: O'Dwyer JL, Meads DM, Hulme CT, Mcparland L, Brown S, Coates LC, Moverley AR, Emery P, Conaghan PG, Helliwell PS. Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic Analysis of a Multicenter Randomized Controlled Trial. Arthritis Care Res (Hoboken). 2018 Mar;70(3):462-468. doi: 10.1002/acr.23293. Epub 2018 Jan 30.
citation: Coates LC, Moverley AR, McParland L, Brown S, Navarro-Coy N, O'Dwyer JL, Meads DM, Emery P, Conaghan PG, Helliwell PS. Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet. 2015 Dec 19;386(10012):2489-98. doi: 10.1016/S0140-6736(15)00347-5. Epub 2015 Oct 1.
citation: Freeston JE, Coates LC, Nam JL, Moverley AR, Hensor EM, Wakefield RJ, Emery P, Helliwell PS, Conaghan PG. Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound. Arthritis Care Res (Hoboken). 2014 Mar;66(3):432-9. doi: 10.1002/acr.22158.
citation: Coates LC, Navarro-Coy N, Brown SR, Brown S, McParland L, Collier H, Skinner E, Law J, Moverley A, Pavitt S, Hulme C, Emery P, Conaghan PG, Helliwell PS. The TICOPA protocol (TIght COntrol of Psoriatic Arthritis): a randomised controlled trial to compare intensive management versus standard care in early psoriatic arthritis. BMC Musculoskelet Disord. 2013 Mar 21;14:101. doi: 10.1186/1471-2474-14-101.