What are the considerations and treatment options for using biologics, such as adalimumab (Humira) and ustekinumab (Stelara), in patients with conditions like rheumatoid arthritis and plaque psoriasis?

Biologics for Rheumatoid Arthritis and Plaque Psoriasis: Treatment Considerations and Options

Adalimumab (Humira) and ustekinumab (Stelara) are effective biologic therapies for moderate-to-severe rheumatoid arthritis and plaque psoriasis, with adalimumab recommended as first-line for patients with psoriatic arthritis and ustekinumab as first-line for plaque psoriasis without arthritis. 1

Mechanism of Action and Indications

• Adalimumab is a human anti-TNF-α monoclonal antibody that binds to soluble and membrane-bound TNF-α, inhibiting its interaction with TNF receptors 1
• Ustekinumab is a human monoclonal antibody that binds to the shared p40 subunit of IL-12 and IL-23, blocking their signaling pathways 2
• Adalimumab is FDA-approved for moderate-to-severe plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, and several other inflammatory conditions 3
• Ustekinumab demonstrates high efficacy in plaque psoriasis with 67% and 72% of patients achieving PASI 75 by week 12 for the 45mg and 90mg doses, respectively 1

Dosing Considerations

• Adalimumab dosing for psoriasis: 80mg subcutaneously initially, followed by 40mg one week later, then 40mg every other week thereafter 1
• For better disease control in some patients, adalimumab maintenance dose may be increased to 40mg weekly 1
• Ustekinumab dosing is weight-based: 45mg for patients <100kg and 90mg for patients >100kg, administered at weeks 0,4, and then every 12 weeks 1
• Dose escalation may be considered for both biologics in cases of inadequate response, particularly in obese patients 1

Efficacy Considerations

• Adalimumab demonstrates 71% PASI 75 response rate at week 16 in plaque psoriasis 1
• Adalimumab is particularly recommended when psoriatic arthritis is present alongside psoriasis 1
• Ustekinumab shows maximal efficacy between weeks 20-24, with maintained response for up to 1.5 years with continued therapy 1
• In direct comparison, ustekinumab has shown superior efficacy to etanercept in psoriasis treatment 4

Safety Considerations

Infection Risk

• All biologics carry increased risk of infections, with TNF inhibitors particularly associated with reactivation of latent tuberculosis 3, 5
• Patients must be screened for latent TB before starting adalimumab and monitored during therapy 3
• Risk of serious infections with certolizumab appears higher than with other TNF inhibitors including adalimumab 5
• Live vaccines are contraindicated during biologic therapy due to risk of infection from vaccine strain replication 1

Other Safety Concerns

• TNF inhibitors carry warnings about increased risk of lymphoma and other malignancies, particularly in children and adolescents 3
• TNF inhibitors should be avoided in patients with multiple sclerosis or other demyelinating diseases 1
• Caution is needed in patients with congestive heart failure; TNF inhibitors should be avoided in NYHA class III or IV CHF 1
• Ustekinumab has a favorable safety profile but long-term data beyond 2 years is limited 4

Perioperative Considerations

• TNF antagonists should be discontinued at least four half-lives prior to major surgery (2 weeks for etanercept, 6-8 weeks for adalimumab, 4-6 weeks for infliximab) 1
• Ustekinumab should be discontinued 12 weeks prior to major surgery 1
• Biologic therapy can be restarted postoperatively if there is no evidence of infection and wound healing is satisfactory 1

Combination Therapy Options

• Adalimumab may be combined with methotrexate to augment efficacy for moderate-to-severe plaque psoriasis (strength of recommendation B) 1
• Combination of adalimumab with topical corticosteroids with or without vitamin D analogues can enhance efficacy (strength of recommendation B) 1
• Adalimumab may also be combined with acitretin, apremilast, cyclosporine, or narrowband ultraviolet phototherapy to augment efficacy 1
• Methotrexate reduces immunogenicity of TNF inhibitors, potentially prolonging their efficacy 1

Monitoring and Follow-up

• Assess response to biologic therapy at appropriate time points (e.g., every 6 months) 1
• Evaluate treatment success based on at least 50% reduction in baseline disease severity and clinically relevant improvement in physical, psychological, or social functioning 1
• Consider switching to an alternative therapy if minimal response criteria are not met or if response is lost over time 1
• Regular monitoring for adverse effects, including periodic laboratory tests, is recommended 1

Special Populations and Situations

• In pregnancy, adalimumab is FDA pregnancy category B, though careful risk-benefit assessment is needed 1
• For patients with palmoplantar pustulosis, TNF inhibitors should be avoided as they show lack of benefit and may even trigger new-onset disease 1
• For acropustulosis (acrodermatitis continua of Hallopeau), TNF inhibitors including adalimumab have shown benefit in case reports 1
• In patients who lose response to one biologic, switching to another biologic agent is recommended over adding another systemic agent 1

Treatment Algorithm for Biologic Selection

1. For patients with moderate-to-severe plaque psoriasis without arthritis: consider ustekinumab as first-line biologic 1
2. For patients with psoriatic arthritis: consider adalimumab as first-line biologic 1
3. For patients who fail first biologic therapy: switch to alternative biologic based on comorbidities and disease characteristics 1
4. For patients with very severe disease or when other biologics have failed: consider infliximab 1