What is the management approach for conditions that wax and wane, such as multiple sclerosis (MS) or rheumatoid arthritis (RA)?

Management of Waxing and Waning Conditions

For conditions that wax and wane like rheumatoid arthritis, the cornerstone of management is aggressive treat-to-target therapy with disease-modifying drugs initiated immediately at diagnosis, combined with frequent monitoring every 1-3 months and rapid treatment adjustment if remission or low disease activity is not achieved within 6 months. 1

Core Treatment Principles

Immediate Initiation of Disease-Modifying Therapy

• Start methotrexate immediately upon diagnosis as the anchor drug, optimized to 15-25 mg weekly within 4-6 weeks, always with folic acid supplementation. 1, 2
• Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) as bridging therapy for up to 6 months maximum, then taper as rapidly as clinically feasible. 1, 2
• The goal is to prevent the "waxing" phases from causing irreversible joint damage and disability. 1

Strict Treat-to-Target Strategy

• Monitor disease activity every 1-3 months using validated composite measures (DAS28-ESR, CDAI) until the treatment target is reached. 1, 2
• The non-negotiable target is sustained remission or low disease activity—not symptom control alone. 1, 2, 3
• If no improvement by 3 months or target not reached by 6 months, immediately adjust therapy. 1, 2

Treatment Escalation Algorithm

First DMARD Strategy Failure

Without poor prognostic factors (low disease activity, no erosions, seronegative):

• Change to another conventional synthetic DMARD (leflunomide, sulfasalazine) or add combination therapy (methotrexate + sulfasalazine + hydroxychloroquine). 1, 2

With poor prognostic factors (high disease activity, erosions present, seropositive, elevated acute phase reactants):

• Add a biologic DMARD immediately—TNF inhibitor (adalimumab, etanercept, infliximab, certolizumab, golimumab) combined with methotrexate. 1
• Alternative biologics include IL-6 inhibitors (tocilizumab), T-cell costimulation inhibitors (abatacept), or B-cell depletion (rituximab). 1

Subsequent Biologic Failure

• After first TNF inhibitor failure, switch to another TNF inhibitor, abatacept, rituximab, or tocilizumab. 1
• JAK inhibitors may be considered as an alternative to biologics. 2

Managing Difficult-to-Treat Disease

When Standard Approaches Fail

For patients meeting difficult-to-treat criteria (≥2 biologics with different mechanisms failed, persistent moderate/high disease activity):

• Reassess the diagnosis—exclude mimicking conditions (non-inflammatory pain, fibromyalgia, osteoarthritis, other inflammatory arthritides). 1
• Verify true inflammatory activity using imaging (ultrasound, MRI) and acute phase reactants, not just symptom scores. 1
• Address non-inflammatory contributors: pain sensitization, depression, poor self-efficacy, non-adherence. 1

Individualized Treatment Goals

• In truly refractory disease with established damage, tailor treatment goals to the individual patient rather than pursuing unrealistic remission targets that lead to unnecessary DMARD cycling. 1
• Consider multimodal treatment packages: aerobic exercise, occupational therapy, psychological interventions (cognitive behavioral therapy), patient education, and self-management programs. 1, 4

Critical Caveats

Glucocorticoid Management

• Never use chronic glucocorticoids as maintenance therapy—they are bridging therapy only, with maximum 6-month duration. 1
• Inability to taper below 7.5 mg/day prednisone defines treatment failure requiring DMARD escalation. 1

Monitoring for Relapse

• Female sex and high baseline ESR (>40 mm/hr) are associated with higher relapse rates and prolonged therapy needs. 1
• During "waning" phases (remission), do not stop DMARDs abruptly—consider cautious tapering of biologics only after sustained remission on combination therapy with a synthetic DMARD. 1

Special Populations

• In multiple sclerosis coexisting with rheumatoid arthritis, avoid TNF inhibitors as they can exacerbate demyelinating disease. 5, 6
• IL-6 inhibitors (tocilizumab) have been used safely in this scenario, though one case report suggests caution. 5, 6
• Interferon beta-1a is FDA-approved for relapsing forms of multiple sclerosis. 7

NSAIDs Are Not Disease-Modifying

• Use NSAIDs at minimum effective dose for shortest duration only for symptomatic relief after assessing GI, renal, and cardiovascular risks. 2, 8
• NSAIDs do not prevent disease progression or structural damage. 2

Shared Decision-Making

• All treatment decisions must be made through shared decision-making between patient and rheumatologist, discussing treatment aims, risks, benefits, and reasons for recommended approaches. 1
• Rheumatologists should primarily manage these patients, though care should be coordinated with primary care in a multidisciplinary approach. 1