Complications of Disease-Modifying Antirheumatic Drug (DMARD) Treatment
DMARDs carry significant risks of infections, malignancies, and organ toxicity that require careful monitoring and management throughout treatment. 1
Infection Risks
Biological DMARDs (bDMARDs) significantly increase the risk of serious infections compared to conventional synthetic DMARDs (csDMARDs), with TNF inhibitors showing a 3.1-fold increased risk and non-TNF biologics showing a 3.9-fold increased risk 1
Specific infection risks include:
- Tuberculosis: Higher risk with monoclonal TNF antibodies compared to etanercept (adjusted odds ratio 2.49) 1
- Herpes zoster: Increased risk with JAK inhibitors (tofacitinib) compared to abatacept (adjusted hazard ratio 2.01) 1
- Opportunistic infections: Similar risk between tocilizumab and TNF inhibitors 1
Combination therapy with multiple biologics significantly increases infection risk without added benefit; therefore, combining TNF blockers with anakinra or abatacept is not recommended 2
Malignancy Risks
Long-term registry data have not confirmed initial fears of increased malignancy risk with most DMARDs, including TNF inhibitors 3
For patients with a history of cancer, the database is smaller but current evidence suggests no substantial increased risk of recurrence with DMARD therapy 3
JAK inhibitors require more surveillance as limited long-term data exists outside of clinical trials; one study showed increased malignancy risk with tofacitinib compared to TNF inhibitors in high-risk patients 3
Organ-Specific Toxicities
Liver toxicity: Methotrexate can cause hepatotoxicity ranging from transient elevation of liver enzymes to fibrosis and cirrhosis in rare cases 4
Retinal toxicity: (Hydroxy)chloroquine can cause irreversible retinopathy, one of the few non-reversible DMARD complications 4
Pulmonary complications: Interstitial lung disease and pulmonary fibrosis can occur with several DMARDs 2
Gastrointestinal perforations: Reported with some biologics, particularly in combination therapy 2
Hematological Complications
Blood dyscrasias: Various DMARDs can cause cytopenias, requiring regular blood count monitoring 4
Neutropenia: More common with certain biologics and can increase infection risk 1
Cardiovascular and Thrombotic Risks
Venous thromboembolism (VTE): Observed with JAK inhibitors in clinical trials 1
Major adverse cardiovascular events (MACE): Require monitoring, particularly in patients with pre-existing cardiovascular risk factors 1
Monitoring Recommendations
More intensive monitoring is required during the first few months of treatment when most adverse reactions occur 4
Standard monitoring includes:
- Complete blood count
- Liver function tests
- Kidney function tests
- Urinalysis
- Ophthalmologic exams (for antimalarials) 4
Tuberculosis screening before initiating bDMARDs and monitoring during treatment 1
Management of Complications
Dose-dependent adverse effects may improve with dose reduction 4
Idiosyncratic reactions often require drug discontinuation 4
Most adverse reactions to DMARDs are reversible if detected early, with exceptions including hydroxychloroquine-induced retinopathy and methotrexate-induced liver cirrhosis 4
For difficult-to-treat patients, especially those with severe complications like macrophage activation syndrome, management in collaboration with expert centers is recommended 1
Special Considerations
Treatment adherence significantly impacts effectiveness and safety; non-adherence rates range from 30-80% in RA patients 1, 5
Patients with comorbidities have higher risk of adverse events and may require adjusted monitoring schedules 1
Glucocorticoids, while effective for controlling inflammation, have significant toxicity in intermediate to long-term use and should be used cautiously for short periods 1
Live vaccines should be avoided in patients on bDMARDs 2
By understanding and proactively monitoring for these potential complications, clinicians can optimize the benefit-risk ratio of DMARD therapy for patients with rheumatoid arthritis and other inflammatory conditions.