What is the first line of treatment for a patient with rheumatoid arthritis (RA) and Sjögren's syndrome overlap who has developed myositis?

First-Line Treatment for Myositis in RA-Sjögren's Overlap

For a patient with rheumatoid arthritis and Sjögren's syndrome overlap who develops myositis, initiate high-dose corticosteroids (0.5-1.0 mg/kg prednisone equivalent) concurrently with a steroid-sparing immunosuppressant, with rituximab being the preferred first-line agent given its efficacy across all three disease manifestations. 1

Rationale for Rituximab as Preferred Agent

Rituximab should be prioritized in this clinical scenario because it addresses inflammatory arthritis, myositis, and Sjögren's syndrome simultaneously. 1 The 2023 ACR/CHEST guidelines specifically note that rituximab may be preferred in the setting of inflammatory arthritis, myositis, or Sjögren neuropathy because of potential effectiveness for treating these manifestations. 1

• Rituximab dosing for this overlap syndrome follows the RA protocol: two 1,000 mg intravenous infusions separated by 2 weeks, with methylprednisolone 100 mg IV (or equivalent) administered 30 minutes prior to each infusion 2
• The drug depletes CD19-positive B cells within 2 weeks, with most patients showing near-complete depletion for at least 6 months 2

Alternative First-Line Immunosuppressants

If rituximab is not feasible due to cost, infection risk, or patient preference, mycophenolate mofetil (1,000-1,500 mg twice daily) represents the next best option as it is conditionally recommended as preferred first-line therapy across systemic autoimmune rheumatic diseases. 1, 3, 4

Additional first-line options include:

• Azathioprine (1-2 mg/kg daily) - requires TPMT testing before initiation to reduce severe leukopenia risk 5
• Cyclophosphamide - reserved for severe or rapidly progressive disease due to higher adverse event profile (infection, cytopenias, hemorrhagic cystitis, infertility) 1

Corticosteroid Management

Initiate prednisone at 0.5-1.0 mg/kg daily (or equivalent methylprednisolone) for active myositis, with a plan for slow taper over 3 months. 1, 5

• The goal is to reduce to ≤10 mg/day prednisone as quickly as tolerated, ideally within 3 months 1, 5
• For long-term management, maintain the lowest effective dose, ideally below 10 mg daily 5, 6
• Taper using 1 mg decrements every 2-4 weeks once disease control is achieved 6
• Always initiate calcium (800-1,000 mg/day) and vitamin D (400-800 units/day) supplementation when starting corticosteroids 6

Critical Monitoring Parameters

Assess treatment response at 3-6 months using:

• Muscle strength examination and functional assessment 1
• Creatine kinase levels (should normalize or significantly decrease) 1
• MRI with T2-weighted and STIR sequences to monitor muscle inflammation 1
• Pulmonary function tests (FVC and DLCO) every 3-6 months, as interstitial lung disease occurs frequently in this overlap population 3, 5

Management of Inadequate Response

If disease remains active or progresses despite first-line therapy at 6 months:

• Add (do not switch) a second immunosuppressant while continuing the first agent 4
• If on mycophenolate, add rituximab 4
• Consider IVIG (2 g/kg divided over 2-5 days monthly) for refractory cases 1
• Evaluate for rapidly progressive disease requiring intensification to dual or triple therapy 1, 4

Common Pitfalls to Avoid

• Do not use corticosteroids as monotherapy - always initiate a steroid-sparing agent concurrently to enable corticosteroid taper and prevent long-term toxicity 1, 5
• Do not delay screening for interstitial lung disease - obtain baseline HRCT and PFTs even without respiratory symptoms, as subclinical ILD is frequent in Sjögren's patients 5
• Do not overlook hepatobiliary involvement - screen for primary biliary cholangitis overlap given the Sjögren's diagnosis 5
• Avoid methotrexate as first-line therapy - it is conditionally recommended against for systemic autoimmune rheumatic disease-associated complications and carries risk of drug-induced pneumonitis 1, 5