What biologics, such as Tumor Necrosis Factor (TNF) inhibitors, Interleukin-17 (IL-17) inhibitors, or Interleukin-23 (IL-23) inhibitors, can be used to treat severe conditions?

Biologic Options for Severe Conditions

For psoriatic arthritis, TNF inhibitors are the first-line biologic choice, followed by IL-17 inhibitors, then IL-12/23 inhibitors, with specific alternatives based on contraindications and disease characteristics. 1

First-Line Biologic Selection

TNF Inhibitors (Preferred Initial Biologic)

• TNF inhibitors are conditionally recommended over IL-17 inhibitors and IL-12/23 inhibitors when switching from oral small molecule therapy in active psoriatic arthritis 1
• Available TNF inhibitors include adalimumab, infliximab, etanercept, golimumab, and certolizumab 2, 3
• TNF inhibitor monotherapy is preferred over combination with methotrexate, though combination may be considered for severe psoriasis, partial MTX response, or when using infliximab/adalimumab to prevent immunogenicity 1

When to Avoid TNF Inhibitors

Absolute contraindications to TNF inhibitors include: 1, 4

• NYHA Class III or IV congestive heart failure (associated with increased mortality) 4
• Active demyelinating disease or family history of multiple sclerosis 1
• Recurrent serious infections 1
• Active tuberculosis 5

Second-Line Biologic Options

IL-17 Inhibitors

• Switch to IL-17 inhibitors (secukinumab, ixekizumab, brodalumab) when TNF inhibitors are contraindicated or have failed 1
• IL-17 inhibitors are conditionally preferred over IL-12/23 inhibitors based on moderate-quality evidence 1
• Particularly appropriate for patients with severe psoriasis and contraindications to TNF inhibitors 1, 4
• IL-17 inhibitors are safe in congestive heart failure patients, unlike TNF inhibitors 6, 4

Important caveat: IL-17 inhibitors increase risk of mucocutaneous Candida infections 6, 5

IL-12/23 Inhibitors

• IL-12/23 inhibitors (ustekinumab) are conditionally recommended when TNF inhibitors are contraindicated 1
• Strongly preferred over IL-17 inhibitors in patients with concomitant inflammatory bowel disease 1
• Offer less frequent administration (every 12 weeks after loading), which may improve adherence 1, 4
• Safe in congestive heart failure patients 6, 4

IL-23 Inhibitors (Newer Generation)

• IL-23 specific inhibitors like risankizumab (Skyrizi) can be used after IL-17 inhibitor failure, particularly when discontinuation was due to Candida infections 6
• No cardiovascular contraindications, making them suitable for patients with heart failure 6

Algorithm for Biologic Selection After Treatment Failure

After TNF Inhibitor Failure

Switch to a different TNF inhibitor first unless: 1

• Primary TNF biologic failure occurred
• Serious adverse event to TNF inhibitor
• Severe psoriasis is present (consider IL-17i or IL-12/23i)
• Recurrent/serious infections (consider abatacept)

If switching to non-TNF biologic: 1

• IL-17 inhibitor preferred over IL-12/23 inhibitor (moderate-quality evidence)
• IL-12/23 inhibitor preferred if concomitant IBD present
• Abatacept considered if recurrent serious infections

After IL-17 Inhibitor Failure

• Switch to TNF inhibitor over IL-12/23 inhibitor (very low-quality evidence) 1
• Consider IL-12/23 inhibitor if severe psoriasis or TNF contraindications exist 1

Special Population Considerations

Congestive Heart Failure

• Absolutely avoid TNF inhibitors in NYHA Class III-IV heart failure 4
• Use IL-17 inhibitors or IL-12/23 inhibitors as first-line biologics 4
• NYHA Class I-II may use TNF inhibitors with extreme caution and close cardiac monitoring 4

Inflammatory Bowel Disease

• Use monoclonal antibody TNF inhibitors (not etanercept) as first-line 1
• Strongly avoid IL-17 inhibitors (shown ineffective and potentially harmful in IBD) 1, 5
• IL-12/23 inhibitors are effective for IBD and strongly preferred over IL-17 inhibitors 1

Recurrent Infections

• Avoid TNF inhibitors 1
• Consider abatacept over other biologics 1
• IL-12/23 inhibitors preferred over IL-17 inhibitors 1

Severe Psoriasis

• IL-17 or IL-12/23 inhibitors may be preferred over TNF inhibitors 1
• Consider combination biologic plus methotrexate therapy 1

Critical Safety Monitoring

Pre-Treatment Requirements

• Screen for active or latent tuberculosis before initiating any biologic 5
• Treat latent TB before starting biologic therapy 5
• Evaluate for active infections 5
• Screen for hepatitis B (risk of reactivation with biologics) 5

Ongoing Monitoring

• Monitor for signs/symptoms of infection during treatment 5
• Discontinue biologic if serious infection develops until resolved 5
• Watch for IBD exacerbations, particularly with IL-17 inhibitors 5
• Monitor for hypersensitivity reactions including anaphylaxis 5

Drug Interactions and Combination Therapy

Avoid Concurrent Use

• Do not combine TNF inhibitors with other biologics (increased infection risk without added benefit) 3
• Avoid live vaccines during biologic therapy 3
• Do not combine with anakinra or abatacept (increased serious infection risk) 3

Methotrexate Combination

• Methotrexate reduces adalimumab clearance but dose adjustment not required 3
• Combination therapy may reduce immunogenicity, particularly with infliximab and adalimumab 1