Arthroscopic Synovectomy of the Wrist in Inflammatory Arthritis (ARCTIC)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Surgery; Psoriatic Arthritis; Wrist Arthritis
• Intervention / Treatment: Drug: Intra-articular corticosteroid injection; Procedure: Arthroscopic synovectomy of the wrist

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Philip d'Ailly, MD; Phone Number: 31102912205; Email: daillyp@maastadziekenhuis.nl
• Study Contact Backup: Name: Christel Deugd-Verburg, MSc; Phone Number: 31102912205; Email: DeugdC@maasstadziekenhuis.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
      • Recruiting
      • Maasstad Hospital
      • Contact: Philip d'Ailly, MD; Phone Number: +3110 291 1911; Email: daillyp@maasstadziekenhuis.nl
      • Contact: Radjesh Bisoendial, MD, PhD; Phone Number: +3110 291 1911; Email: bisoendialr@maasstadziekenhuis.nl
      • Sub-Investigator: Philip d'Ailly, MD
      • Principal Investigator: Radjesh Bisoendial, MD, PhD
      • Sub-Investigator: Niels Schep, MD, PhD
      • Sub-Investigator: Marc Kok, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intra-articular corticosteroid injection; Injection with 40mg triamcinolone acetonide (kenacort) in the wrist	Drug: Intra-articular corticosteroid injection; Injection with 40mg triamcinolone acetonide (kenacort) in the wrist
Experimental: arthroscopic synovectomy; Wrist arthroscopy in day surgery setting with debulking of synovitis, inspection of cartilage, ligament, tendon and bone damage, collection of synovial biopsies and deposition of intra-articular corticosteroids (40mg triamcinolone acetonide)	Procedure: Arthroscopic synovectomy of the wrist; Wrist arthroscopy in day surgery setting with debulking of synovitis, inspection of cartilage, ligament, tendon and bone damage, collection of synovial biopsies and deposition of intra-articular corticosteroids (40mg triamcinolone acetonide)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Rated Wrist evaluation (PRWE)	15-item questionnaire scoring pain and wrist function on a scale from 0-100, with a higher score indicating worse outcome.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Rated Wrist evaluation (PRWE)	15-item questionnaire scoring pain and wrist function on a scale from 0-100, with a higher score indicating worse outcome.	6 and 12 months
Wrist ultrasound	Resolution of ultrasound (US) arthritis as defined by grey scale (B-mode) and power Doppler after three months compared to baseline measurement. Grey scale uses a two-dimensional image to visualize structural changes like synovial hypertrophy and bone erosions. Power Doppler mode can assess joint inflammatory activity by detecting pathological synovial blood flow. The EULAR-OMERACT (Outcome Measures in Rheumatology Clinical Trials) combined scoring system includes both greyscale and power Doppler and will be used to score arthritis in this study. Ultrasound has demonstrated greater sensitivity than clinical assessment and conventional radiography for detecting synovitis in RA target joints. Also, US signs of synovitis were found predictive for flare and failure of DMARD therapy, despite clinical remission. Furthermore, ultrasound techniques are low-invasive, inexpensive and require no radiation.	3 months
Wrist X-ray	Standard (plain) radiographs of the wrist at baseline and after twelve months. Arthritis on radiographs will be graded using the Modified Larsen grading system. This system grades wrist arthritis on a score of 0 to 5, 5 indicating the most joint abnormalities.	12 months
NRS pain score	Numeric Rating Scale (NRS) pain score at baseline two, four and six weeks (by phone), and at three, six and twelve months (digitally). A score of 0 implies no pain and 10 the worst possible pain.	2, 4 and 6 weeks, 3, 6 and 12 months
Range of motion	Range of motion (ROM) of the wrist at baseline, three, six and twelve months. ROM will be measured actively with a goniometer and includes pronation, supination, ulnar and radial deviation and palmar and dorsal flexion.	3, 6 and 12 months
Grip strength	Grip strength of the wrist at baseline, three, six and twelve months. Grip strength will be measured using a dynamometer as the mean of three measurements.	3, 6 and 12 months
DAS 28	EULAR response rate and Disease Activity Score (DAS28) at baseline, three, six and twelve months. The DAS28 is a measure of disease activity in rheumatoid arthritis in which 28 joints are examined for swelling and tenderness, combined with global pain scores and blood markers (www.DAS28-score.nl). The EULAR response rate measures responsiveness to anti-rheumatic treatment and is derived from the DAS28 score	3, 6 and 12 months
EQ-5D	EuroQol 5D (EQ-5D) at baseline, three, six and twelve months. The EQ-5D is a standardized questionnaire scoring quality of life on five different levels, on a scale from 0-100.	3, 6 and 12 months
iPCQ questionnaire	Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) at baseline, three, six and twelve months. The iPCQ is a standardized instrument for measuring and valuing health related productivity losses. This wil be used for the cost effectiveness analysis.	3, 6 and 12 months
iMCQ questionnaire	Institute for Medical Technology Assessment (iMTA) Medical Consumption Questionnaire (iMCQ) at baseline, three, six and twelve months. The iMCQ is a standardized instrument for measuring medical costs. The iMCQ includes questions related to frequently occurring contacts with health care providers, medication use and home care. This wil be used for the cost effectiveness analysis.	3, 6 and 12 months
ESR	Laboratory test: erythrocyte sedimentation rate (ESR) at baseline and three, six and twelve months (part of the routine clinical care).	3, 6 and 12 months
CRP	Laboratory tests: C-reactive protein (CRP) at baseline and three, six and twelve months (part of the routine clinical care).	3, 6 and 12 months
Adverse events	Adverse events (AEs) (including glucocorticoid related AEs), AEs leading to withdrawal, AEs leading to discontinuation of medication, and AEs due to infusion reactions.	One year

Collaborators and Investigators

• Sponsor: Maasstad Hospital
• Investigators: Principal Investigator: Radjesh Bisoendial, MD, PhD, Maasstad Ziekenhuis

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 27, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Psoriatic Arthritis; Rheumatoid arthritis; Wrist arthroscopy; Arthroscopic synovectomy; Patient related outcome
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic
• Other Study ID Numbers: ARCTIC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No