What are the management and monitoring recommendations for a patient with an autoimmune condition, such as rheumatoid arthritis, taking Hydroxychloroquine (Plaquenil) and Humira (Adalimumab)?

Management and Monitoring of Hydroxychloroquine and Humira (Adalimumab) Combination Therapy

For patients with rheumatoid arthritis taking hydroxychloroquine and adalimumab, continue both medications without interruption, as hydroxychloroquine provides additional disease control and may have protective effects, while adalimumab addresses the underlying inflammatory process. 1

Rationale for Combination Therapy

The combination of hydroxychloroquine with adalimumab is supported by current rheumatology guidelines, though hydroxychloroquine alone is considered insufficient for active RA. The 2020 EULAR guidelines note that hydroxychloroquine monotherapy has "only weak clinical and no structural efficacy" for RA in general, but it can be continued as adjunctive therapy when combined with more potent agents like TNF inhibitors. 1

• Adalimumab serves as the primary disease-modifying agent, addressing active inflammation and preventing structural damage 1
• Hydroxychloroquine provides complementary benefits including potential cardiovascular protection and additional immunomodulation 2
• The 2016 ACR guidelines explicitly allow continuation of hydroxychloroquine alongside biologic DMARDs like adalimumab 1

Critical Monitoring Requirements for Adalimumab

Pre-Treatment and Ongoing Infection Surveillance

Before initiating or continuing adalimumab, mandatory screening includes tuberculin skin testing, chest radiograph, and hepatitis B serology. 1, 3

• TB screening is non-negotiable: Adalimumab carries higher TB reactivation risk (171 per 100,000 patient-years) compared to other TNF inhibitors 4
• Patients may have false-negative tuberculin skin tests while on immunosuppression, but M. tuberculosis-specific interferon-gamma testing remains reliable 1
• Serious infection rate is 2.03 per 100 patient-years in long-term studies 1, 3

Specific Infection Risks to Monitor

Watch vigilantly for atypical and opportunistic infections:

• Legionella pneumophila pneumonia (cluster cases reported) 1
• Pneumocystis jirovecii pneumonia 1, 3
• Atypical mycobacteria 1, 3
• Deep fungal infections, particularly in endemic areas 3

If any infection develops, pause adalimumab immediately for the duration of the infection and treat aggressively with appropriate antimicrobials. 1, 5 The one exception is that hydroxychloroquine should be continued during infections, as it may have therapeutic potential against certain pathogens. 1

Laboratory Monitoring Schedule

For adalimumab: No routine laboratory monitoring is required after baseline screening, but maintain high clinical suspicion for infection signs 1

For hydroxychloroquine: No laboratory monitoring is needed after baseline assessment 1

Medication	<3 months	3-6 months	>6 months
Hydroxychloroquine	None after baseline	None	None
Adalimumab	Clinical monitoring only	Clinical monitoring only	Clinical monitoring only

1

Ophthalmologic Monitoring for Hydroxychloroquine

Baseline ophthalmologic examination is required before starting hydroxychloroquine, with annual screening beginning after 5 years of use (or sooner if risk factors present). 2

• Retinal toxicity is rare but serious, occurring primarily with long-term use 2
• Risk factors include cumulative dose >1000g, duration >5 years, renal disease, and concurrent tamoxifen use 2
• Retinopathy risk increases significantly after 5 years of therapy 2

Autoimmune and Pulmonary Complications

Be alert for paradoxical autoimmune reactions with adalimumab:

• Lupus-like syndrome: Reported in 15 patients treated with adalimumab 3
• Vasculitis: Documented in 5 cases with adalimumab 3
• Pulmonary fibrosis: Can occur as new event or exacerbation of underlying disease 1, 3
• Interstitial pneumonias: Reported in at least 18 patients on anti-TNF agents 1, 3
• Sarcoidosis: Paradoxically reported with TNF inhibitors despite their use in treating sarcoidosis 1

Hematologic Monitoring

While routine CBC monitoring is not required for either medication individually, check CBC if clinical signs of cytopenia develop (fatigue, bleeding, recurrent infections). 3

• Cytopenias including pancytopenia can occur with adalimumab, though uncommon 3
• Consider hematology consultation for serious hematologic effects 3

Patient Education Priorities

Instruct patients to report immediately:

• Fever or signs of infection (most critical warning sign) 3
• Persistent cough or shortness of breath 1
• Unexplained weight loss or night sweats (TB symptoms) 1
• New or worsening joint pain (paradoxical arthritis) 3
• Visual changes (hydroxychloroquine retinopathy) 2

Patients must avoid live vaccines during adalimumab therapy. 3

Dosing Considerations

Adalimumab: 40 mg subcutaneously every other week is standard dosing for RA. 6 Methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics may be continued. 6 Some patients not taking concomitant methotrexate may benefit from increasing to 40 mg weekly or 80 mg every other week. 6

Hydroxychloroquine: Maximum 400 mg/day (up to 7 mg/kg/day), typically started at half-dose for 2 weeks to assess tolerability. 7

Special Populations

Pregnancy: Adalimumab is FDA Category B for all trimesters, with increased first-trimester miscarriage rates reported. 1, 3 Safety in breastfeeding is unknown, with antibodies secreted in milk. 3

Elderly patients: No dose adjustment required, but maintain heightened vigilance for infections given age-related immunosenescence. 1

When to Consider Therapy Modification

Do not discontinue either medication without clear indication. 1 Consider modification only if:

• Active infection develops (pause adalimumab only) 1, 5
• Confirmed retinal toxicity from hydroxychloroquine (discontinue hydroxychloroquine) 2
• Serious adverse events attributable to either medication 3
• Inadequate disease control after 3-6 months (consider adding or switching agents per treatment algorithm) 1

The combination of hydroxychloroquine and adalimumab is rational and guideline-supported for RA management, with the primary monitoring focus on infection surveillance for adalimumab and ophthalmologic screening for hydroxychloroquine.