Primary Sjögren's syndrome (PSS) Musculoskeletal Diseases Other systemic involvement of connective tissue
Conditions
Interventions
Patients will receive two doses of rituximab (1000 mg) or placebo by intravenous (IV) infusion given with IV methylprednisolone (100 mg) at 2 week intervals at T = 0 and T = 2 weeks. This will be repe
Sponsors
University of Leeds (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 20/09/2011: 1. Aged between 18 and 80 years of age. 2. A confirmed diagnosis of primary Sjögren?s syndrome by AECG criteria (see Appendix B). 3. Positive for anti-Ro auto-antibodies. 4. Patients with a diagnosis of primary Sjögren?s syndrome (by AECG criteria) with more than 10 years disease duration must have at least one systemic feature of: 4.1 Hypergammaglobulinaemia (IgG over 16)*, or 4.2 Low complement C4*, or 4.3 Cryoglobulinaemia OR 4.4 Active/past history since diagnosis of the following (ascribed to Sjögren?s Syndrome): 4.5 purpura/cutaneous vasculitis, 4.6 lymphadenopathy, 4.7 persistent parotid salivary gland swelling not due to infection, 4.8 peripheral neuropathy (previously documented by nerve conduction tests), 4.9 interstitial lung disease confirmed by HRCT, 4.10 renal tubular acidosis requiring treatment, 4.11 CNS disease ascribed to Sjögren?s syndrome (confirmed by MRI), 4.12 myositis (CPK>2N and EMG or biopsy evidence of myositis), 4.13 inflammatory arthritis 5. An unstimulated salivary flow rate greater than 0ml in 15 minutes. 6. Symptomatic oral dryness (= 5/10 on patient-completed Likert**). 7. Symptomatic fatigue (= 5/10 on patient-completed Likert**). 8. Patients on corticosteroids, NSAIDS, antidepressants, methotrexate, or pilocarpine*** must have been on a stable dose for 4 weeks prior to receiving the first infusion of study medication and expected to remain on this dose throughout the study. 9. Patients who are on hydroxychloroquine at screening must have been on a stable dose throughout the preceding six-month period. If they have stopped hydroxychloroquine they should have been off it for at least 3 months prior to receiving study medication. 10. Given their written informed consent to participate in the trial and expected to be able to adhere to the study visit schedule and other protocol requirements. *Anti-Ro antibody test, IgG, RF and C4 assays performed within 6 months of screening may be used to confirm eligibility. If greater than 6 months repeats should be performed locally at screening to confirm eligibility. ** LIKERT range 0-10 with 10 corresponding to worst severity. *** Pilocarpine or drugs with similar pharmacological action should not be used within 12 hours of the assessment visits at screening, baseline, week 16, week 24, week 36 and week 48 (end of study). Previous inclusion criteria: 1. Aged between 18 and 80 years of age, either sex 2. A confirmed diagnosis of of primary Sjögrens syndrome by American?European Consensus Group (AECG) criteria with: 2.1. Positive labial gland biopsy** and/or 2.2. Positive for anti-Ro auto-antibodies greater than 1.5 upper limit of normal* 3. A stimulated salivary flow rate of greater than or equal to 0.5 ml in 5 minutes 4. An unstimulated salivary flow rate greater than 0 in 15 minutes 5. Be positive for anti-Ro auto-antibodies greater than 1.5 upper limit of normal 6. Symptomatic oral dryness (greater than or equal to 5/10 on patient-completed Likert***) 7. Symptomatic fatigue (greater than or equal to 5/10 on patient-completed Likert***) 8.1. At least one systemic feature of: 8.1.1. Hypergammaglobulinaemia (IgG over 16)*, or 8.1.2. Low complement C4*, or 8.1.3. Cryoglobulinaemia 8.2. Active/past history since diagnosis of the following (ascribed to Sjögrens syndrome): 8.2.1. Inflammatory polyarthritis 8.2.2. Purpura/cutaneous vasculitis 8.2.3. Lymphadenopathy 8.2.4. Persistent parotid sali
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 20/09/2011: 1. Diagnosis of secondary Sjögren?s syndrome. 2. Use of DMARDs, immunosuppressant therapies or antidepressants within 4 weeks prior to the first dose administration (except for glucocorticoids, salicylates, non-steroidal anti inflammatory drugs (NSAIDs), methotrexate and analgesics which are acceptable). 3. Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished. 4. Men whose partners are of child-bearing potential but who are unwilling to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished. 5. Patient has active or prior hepatitis B or C, known HIV positivity or known history of tuberculosis. 6. Any history of other autoimmune diseases or other form of immunodeficiency or neutropaenia 3 months prior to study entry). 19. Presence of a clinically significant illness or mental disorder within 4 weeks of the start of the trial where the safety of the individual might be at risk by entry into the trial, or where the individual does not have the capacity to consent or where the outcome of the therapy cannot be assessed by virtue of the illness or disorder. Each patient will be assessed individually and no person who wishes to participate will be unreasonably excluded by virtue of the illness or disorder. Previous exclusion criteria: 1. Diagnosis of secondary Sjögrens syndrome 2. Us
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A 30% reduction at 48 weeks from baseline in either oral dryness or fatigue measured using visual analogue scales (VAS; range 0 - 100 mm) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Fatigue (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 2. Oral dryness (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 3. Ocular dryness (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 4. Patient global assessments (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 5. Physician global assessments (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 6. Salivary flow (stimulated and unstimulated salivary flow), performed at baseline, 16, 24, 36 and 48 weeks 7. Lachrymal flow (Schirmers I test of ocular function), performed at baseline, 16, 24, 36 and 48 weeks 8. Quality of life, evaluated at baseline and 16, 24, 36 and 48 weeks using the EULAR Sjögrens Syndrome Patient Reported Index (ESSPRI) 9. Quality of life, disease damage and disease activity indices, evaluated at baseline, 24 and 48 weeks using the following: 9.1. Sjögrens Syndrome Disease Damage Index (SSDDI) 9.2. Social Security Disability Insurance (SSDI) 9.3. EULAR Sjögrens Syndrome Disease Activity Index (ESSDAI) 9.4. Sjögrens Syndrome Disease Activity Index (SSDAI) 9.5. Sjögrens Systemic Clinical Activity Index (SCAI) 9.6. 36-item Short Form Health Survey (SF-36) 9.7. Profile of Fatigue and Discomfort?Sicca Symptoms Inventory (PROFAD-SSI) 10. Serological and peripheral blood inflammatory features (haematology biochemistry, serology and immunology assays), taken at baseline, weeks 16, 24, 26, 36 and 48 11. Incremental cost-effectiveness ratio (EQ-5D, health economics) evaluated at baseline, weeks 24 and 48 | — |
Countries
United Kingdom
Outcome results
None listed