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OT 2 - Improvement of hand dysfunction by arthritis

Besides digital ulcers, arthritis may also affect deterioration of hand function in patients with Systemic Sclerosis. Thus, this study aims to identify the incidence of arthritis, potential predictors for its onset, and the best treatment strategy of arthritis.

The following protocol gives you a brief overview about observational trail 2:

 

Protocol Summary                                          PI: László CZIRJÁK

 Investigative objective

Beside skin involvement, digital ulcers, tendinitis, calcinosis and flexion contractures, the presence of hand arthritis is a major contributor to impairment of hand function in systemic sclerosis. Several immunomodulatory drugs used in other rheumatic diseases (including Methotrexate, Leflunomide, Azathioprine, Mycophenolate Mofetil and low-dose Corticosteroids) can potentially improve arthritis and consequently hand function in systemic sclerosis. For the assessment of arthritis, the CDAI (clinical disease activity index) is validated in rheumatoid arthritis, and may be useful for SSc-related arthritis, too.

Aim of this observational trial is to:

  • investigate the efficacy and safety of different treatments on hand dysfunction in systemic sclerosis patients with hand arthritis and
  • to validate the CDAI for arthritis in systemic sclerosis.

 Primary endpoint(s)

 Improvement from baseline in HAQ-DI (CHAQ-DI in jSSc) at 12 months (Time Frame: 12 months)

 Secondary endpoint(s)
  •  Improvement from baseline in HAQ-DI (CHAQ-DI in jSSc) at 24 months (Time Frame: 24 months)
  • Improvement from baseline in CHFS at 12 months (Time Frame: 12 months)
  • Improvement from baseline in CHFS at 24 months (Time Frame: 24 months)

 Exploratory endpoints
  •  Validation of the CDAI in systemic sclerosis (Time Frame: 12 months)
  • Validation of the SDAI in systemic sclerosis (Time Frame: 12 months)
  • Validation of the DAS28(ESR) in systemic sclerosis (Time Frame: 12 months) 
  • Validation of the DAS28(CRP) in systemic sclerosis (Time Frame: 12 months)
  • Validation of the 28 JTC ± hand DIP joints in systemic sclerosis (Time Frame: 12 months)
  • Validation of the 28 JSC ± hand DIP joints in systemic sclerosis (Time Frame: 12 months) 
  • Evaluation of the incidence and potential predictors of deterioration of hand dysfunction and progression of arthritis in systemic sclerosis (Time Frame: 24 months)

 Safety endpoints
  •  Incidence of drug-related adverse events (Time Frame: 24 months)
  • Incidence of withdrawal from treatment due to drug-related adverse events (Time Frame: 24 months)

 Participants

Study population justification

 The study population is adult and juvenile systemic sclerosis patients from the EUSTAR cohort (MEDSonline database) and the jSScWG cohort.

 Inclusion criteria
  •  Juvenile and adult Systemic sclerosis patients, with diagnosis according to the ACR/EULAR adult SSc criteria and PRES/ACR/EULAR juvenile SSc criteria respectively
  • Clinical signs of arthritis (defined as ≥2 tender and swollen joints)
 Exclusion criteria
  • Previous use of stem cell tansplantation   
  • Previous lung transplantation
  • Presence of significant, long standing articular pain due to other cause than SSc (trauma, severe osteoarthritis with active inflammation, psoriatic arthritis with hand involvement, chronic gout, etc.)
  • Acute infection (during the past 4 weeks), that can interfere with the acute phase reactants (ESR, CRP) of the patient (pulmonary, genitourinary, gastrointestinal, skin or systemic infection)
  • Presence of hand disability caused by other, than SSc (stroke, significant trauma etc. affecting hand function)
  • One or more endstage internal organ involvement (Hyperalimentation required at present, Oxygen required at present, Left ventricle ejection fraction<30% measured at the latest echocardiography, Dialysis required at present)
  • Presence of current, digital ulcer at baseline
  • Presence of fibromyalgia (according to the physicians opinion and medical history of the patient)

Trial design

 Observational trial with 4 treatment arms

 Treatment arms

Four different groups will be observed for analysis:

  1. methotrexate with or without low-dose corticosteroids

  2. Other DMARDs (leflunomide, azathioprine, mycophenolic acid) with or

    without low-dose corticosteroids

  3. Low-dose corticosteroids without DMARDs

  4. No DMARD or corticosteroid treatment

Patients, who receive drug(s) related to the observational treatment arms at a dose lower than the minimally efficient dose defined in the table below, will be excluded from the observational treatment arms for primary analysis but will be followed within OT2 for explorative analysis.

In case of therapy changes during the follow-up, only patients who continuously received the drug(s) − related to the observational treatment arms − for at least 9 months during the 1 year follow-up will be included in the observational treatment arms for primary analysis, otherwise they will be excluded from primary analysis but will be followed within OT2 for explorative analysis.

In case of rarely used combination therapies, depending on the period of use and the dose of the respective therapies, the in- or exclusion of patients from the observational treatment arms will be decided one-by-one.

Patients, who received a biologic therapy 3 to 12 months before the baseline visit* and/or a concomitant biologic therapy during the follow-up period, will be excluded from the observational treatment arms for primary analysis but will be followed within OT2 for explorative analysis.

*3 months before baseline in case of Abatacept, Tocilizumab and TNF-alfa antagonists, 12 months in case of Rituximab and “other biologic therapy”. 
ClinicalTrials.gov Identifier:  NCT01834157

For further Information:
http://clinicaltrials.gov/ct2/show/NCT01834157?term=desscipher&rank=2