Clinical trial NCT04755127: Arthroscopic Synovectomy of the Wrist in Inflammatory Arthritis
Official title: ARthroscopiC SynovecTomy Versus Intra-Articular Injection of Corticosteroids for the Management of Therapy Refractory Psoriatic or Rheumatoid Arthritis of the Wrist: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Wrist Arthritis
Psoriatic Arthritis
Rheumatoid Arthritis
Surgery
Keywords: Wrist arthroscopy
Arthroscopic synovectomy
Rheumatoid arthritis
Psoriatic Arthritis
Patient related outcome
Lead sponsor: Maasstad Hospital
Sponsor class: OTHER
First posted: 2021-02-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: non-blinded randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Rationale: Psoriatic (PsA) and rheumatoid arthritis (RA) are inflammatory joint diseases that often involve the wrist and may result in progressive joint destruction followed by impaired wrist function and reduced quality of life. The first line treatment usually consists of conventional Disease-Modifying Anti-Rheumatic Drugs (cDMARDs) along with bridging therapy using systemic corticosteroids or intra-articular corticosteroids in case of limited joint disease. After initiation therapy, intra-articular corticosteroids are often utilized as they provide rapid dampening of joint inflammation in case of a flare-up of disease activity (mono- or oligoarthritis). However, a substantial part of these patients clinically respond poorly or not at all. Alternatively, arthroscopic synovectomy may provide substantial relieve of symptoms, improve functionality, slow down disease progression and prevent joint destruction, as earlier studies have suggested. Prospective randomized studies are needed to confirm these findings. Moreover, they may prevent the need for expensive biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) and assist in guiding therapeutic strategies in the long run, through collecting and analysing valuable synovial biopsies. Wrist arthroscopy is a routine procedure in the participating centres with only minor complications and fast recovery.

Objective: To compare arthroscopic synovectomy with deposition of intra-articular corticosteroids (DIACS) versus intra-articular injection of corticosteroids (IACSI) in RA and PsA patients with mono- or oligoarthritis of the wrist that is refractory to cDMARD therapy.

Study design: Multi-centre randomized controlled trial conducted in the Maasstad Hospital and Spijkenisse Medisch Centrum (SMC).

Study population: Patients with active RA or PsA and bDMARD-naive, who develop a localized flare of disease activity (mono- or oligoarthritis) that involves the wrist, defined as an increase in DAS28 \> 1.2 or \> 0.6 if DAS28 ≥ 3.2 compared to the last DAS28 measurement (maximum six months before) and that is refractory to systemic cDMARD for at least three months, defined as no response on the European League Against Rheumatism (EULAR) response criteria.

Intervention: This study will randomize between IACSI of the wrist (control) and arthroscopic synovectomy of the wrist combined with DIACS (intervention). During arthroscopy synovial biopsies will be collected and stored for later analysis of the functional and histological characteristics of the synovium (beyond the scope of this study).

Main study parameters/endpoints: Primary outcome is the change in Patient-Rated Wrist Evaluation (PRWE) score from randomization to three months of follow-up. The PRWE is a validated, fifteen-item self-reported questionnaire rating wrist pain and function. Secondary outcomes are resolution of wrist arthritis measured by ultrasound, standard wrist radiographs, DAS28, EULAR response rate, Visual Analogue Scale (VAS), EQ-5D quality of life questionnaire, iMTA Productivity Cost Questionnaire (iPCQ), iMTA Medical Consumption Questionnaire (iMCQ), cost effectiveness analyses (CEA), physical examination, adverse events (AE) and laboratory results. Follow-up visits are scheduled at three, six and twelve months after intervention.

Nature and extent of the burden and risks associated with study participation:

Both study arms include standard treatment of care. Wrist arthroscopy is a standard treatment for wrist arthritis and often implemented for other intra-articular wrist pathology. The risks include infection, neurovascular damage and articular surface damage. Nevertheless, wrist arthroscopy is a well-established and safe technique. Reduction of risks will be done according to inclusion and exclusion criteria. If complications arise, the treating physician will proportionate the adequate treatment according to the current protocols based on the published literature. Patients will be asked to return at three, six and twelve months. These visits are standard of care following the rheumatic arthritis protocol. Patients will be asked to complete questionnaires at baseline and at three follow-up moments. These will take 160 minutes in total. The arthroscopy group will return between ten to fourteen days for wound inspection. All patient will be contacted by telephone at two, four and six weeks for VAS pain scores.

Expected results: We expect that arthroscopic synovectomy followed by DIACS will lead to significantly more improvement in PRWE scores compared to IACSI three months after intervention. Furthermore, we anticipate that wrist arthroscopy will result in lower pain scores, better joint mobility, better response on EULAR score, sustained resolution of arthritis on ultrasound, less joint damage on radiographs and is more cost-effective after one-year analysis.


Eligibility criteria: Inclusion criteria In order to be eligible to participate in this study, a subject must meet all of the following criteria:

* Male and female patients with age ≥ 18 years
* Subjects able and willing to give written informed consent (or legally acceptable representative or impartial witness when applicable) and is available for entire study
* Patients meet the criteria of either group below:

Group 1. Inclusion criteria RA patients:

* Patients that are diagnosed with RA according to the revised 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Rheumatoid Arthritis Classification Criteria (table 1)
* Patients are experiencing an exacerbation defined as an increase in DAS28 \> 1.2 or \> 0.6 if DAS28 ≥ 3.2 compared to last DAS28 measurement (maximum six months before)
* The exacerbation is refractory to systemic cDMARDs for at least three months, defined as 'no response' according to the EULAR response criteria (table 2)
* Wrist arthritis, that is diagnosed clinically, is the predominant symptom

Group 2. Inclusion criteria PsA patients:

* Patients that are diagnosed with PsA according to the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria (table 3)
* Patients are experiencing an exacerbation defined as an increase in DAS28 \> 1.2 or \> 0.6 if DAS28 ≥ 3.2 compared to last DAS28 measurement (maximum six months before)
* The exacerbation is refractory to systemic cDMARDs for at least three months, defined as 'no response' according to the EULAR response criteria (table 2)
* Wrist arthritis, that is diagnosed clinically, is the predominant symptom

Exclusion criteria A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Previous or current treatment with biological (b) DMARDs
* Current inflammatory joint disease other than RA or PsA (e.g. gout, reactive arthritis, Lyme disease)
* Subjects who are pregnant or intend to become pregnant during the study
* Intra-articular corticosteroids injection in the wrist in the last 6 months
* Previous wrist surgery
* Severe osteoarthritis with malformations of the wrist
* Congenital abnormalities of wrist function or motion

Primary outcomes:
measure: Patient-Rated Wrist evaluation (PRWE)
timeFrame: 3 months
Secondary outcomes:
measure: Patient-Rated Wrist evaluation (PRWE)
timeFrame: 6 and 12 months
measure: Wrist ultrasound
timeFrame: 3 months
measure: Wrist X-ray
timeFrame: 12 months
measure: NRS pain score
timeFrame: 2, 4 and 6 weeks, 3, 6 and 12 months
measure: Range of motion
timeFrame: 3, 6 and 12 months
measure: Grip strength
timeFrame: 3, 6 and 12 months
measure: DAS 28
timeFrame: 3, 6 and 12 months
measure: EQ-5D
timeFrame: 3, 6 and 12 months
measure: iPCQ questionnaire
timeFrame: 3, 6 and 12 months
measure: iMCQ questionnaire
timeFrame: 3, 6 and 12 months
measure: ESR
timeFrame: 3, 6 and 12 months
measure: CRP
timeFrame: 3, 6 and 12 months
measure: Adverse events
timeFrame: One year
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
state: Zuid-Holland
Study officials:
affiliation: Maasstad ziekenhuis
name: Radjesh Bisoendial, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: