What are the dos and donts for switching and mixing biologic therapies in hidradenitis suppurativa?

Switching and Mixing Biologics in Hidradenitis Suppurativa: Dos and Don'ts

When switching biologics in HS, DO switch directly without washout periods if the patient is experiencing inadequate response or loss of efficacy, as approximately 40% of non-responders at 12 weeks may achieve response with continued or alternative therapy, and DO NOT routinely combine two biologics simultaneously as there is no evidence supporting this practice and it increases infection risk.

DO's for Switching Biologics

DO Switch When Indicated

• Switch after 12-16 weeks of adequate dosing if the patient fails to achieve HiSCR (Hidradenitis Suppurativa Clinical Response) 1
• Continue treatment beyond initial non-response in some cases - nearly 40% of week-12 non-responders to adalimumab achieved response at week 36 with continued treatment 1
• Switch directly between biologics without mandatory washout periods when disease is active

DO Consider Specific Switching Patterns

• From anti-TNF to IL-17 inhibitors (secukinumab) - this is a logical second-line choice given different mechanism of action 2
• From one anti-TNF to another anti-TNF - infliximab may work when adalimumab fails, though evidence is limited 3
• To IL-12/23 inhibitors (ustekinumab) as an alternative pathway when TNF inhibitors fail 3

DO Optimize Dosing Before Switching

• Increase adalimumab to weekly dosing (from every-other-week) before declaring treatment failure - weekly dosing achieved 17.6% response vs 9.6% with every-other-week dosing 1
• Consider therapeutic drug monitoring to assess for antibody formation or subtherapeutic levels before switching 2

DO Use Adjunctive Therapy

• Add methotrexate to prevent anti-TNF antibody formation if indicated, as it does not increase malignancy risk 4
• Continue appropriate antibiotics during biologic therapy - 19% of PIONEER 2 patients continued tetracycline-class antibiotics with adalimumab 1
• Stack treatments - combine biologics with topical therapies, hormonal agents, and lifestyle modifications 5

DON'T's for Switching and Mixing

DON'T Combine Two Biologics Simultaneously

• No evidence supports dual biologic therapy in HS, and this significantly increases infection risk
• Avoid combining anti-TNF agents with other biologics without compelling reason and infectious disease consultation

DON'T Switch Too Early

• DON'T abandon therapy before 12 weeks - initial non-response doesn't predict long-term failure 1
• DON'T switch during the loading phase - allow adequate time for therapeutic levels to be achieved
• DON'T ignore that nearly half of week-12 responders lost response at week 36 - this is expected disease behavior, not necessarily treatment failure 1

DON'T Ignore Special Populations

In patients with malignancy history:

• DON'T use anti-TNFs within 5 years of malignancy - consider secukinumab or ustekinumab instead 4
• DO use anti-TNFs if malignancy remission >5 years in non-high-risk cancers 4
• DO consult oncology before initiating or switching biologics 4

In patients at high TB risk:

• DON'T use anti-TNFs as first choice - consider non-anti-TNF biologic classes 4
• DON'T start anti-TNFs without TB screening (TST and/or IGRA) 4
• DO start prophylactic antibiotics at least 1 month before anti-TNF initiation in latent TB 4

DON'T Overlook Combination Therapy Evidence

• Limited data exists for specific combinations - most evidence is from small retrospective series 6
• Promising combinations include:
  • Isotretinoin or doxycycline with adalimumab for moderate disease 6
  • Cyclosporine with adalimumab for severe disease 6
• These are NOT standard practice and should be reserved for refractory cases

Critical Pitfalls to Avoid

Loss of Response is Common

• Almost 50% of initial responders lose response by week 36 despite continued weekly adalimumab 1
• This represents disease biology, not necessarily treatment failure
• Consider dose escalation, adding adjunctive therapy, or switching mechanism of action

Inadequate Initial Dosing

• Starting with every-other-week adalimumab when weekly dosing shows superior efficacy (17.6% vs 9.6% response) 1
• The FDA-approved regimen is 160mg week 0, 80mg week 2, then 40mg weekly starting week 4 1

Switching Without Optimization

• Check for anti-drug antibodies before switching within the same class 2
• Assess adherence - patient-reported adherence may not reflect actual dosing
• Evaluate for concurrent infections that may mimic treatment failure

Ignoring the Multimodal Approach

• Biologics alone are insufficient - complete response is rare (15%) and partial response occurs in ~50% 3
• Continue wound care, pain management, and lifestyle modifications during biologic therapy 5
• Consider surgical intervention for established tunnels and scarring that won't respond to medical therapy

Practical Switching Algorithm

1. At 12-16 weeks: Assess HiSCR response

   • If no response: Check drug levels/antibodies → Switch to different mechanism
   • If partial response: Optimize dose (increase frequency) or add adjunctive therapy
   • If good response: Continue and monitor

2. If losing response after initial success:

   • Check for anti-drug antibodies
   • Increase dosing frequency if possible
   • Add methotrexate to reduce antibody formation
   • If persistent loss: Switch to different mechanism of action

3. Switching sequence based on evidence:

   • First-line: Adalimumab (FDA-approved) or Secukinumab (FDA-approved) 2
   • Second-line: Switch between these two (different mechanisms)
   • Third-line: Consider ustekinumab or infliximab off-label 3

The key principle: Switching is evidence-based and common, but mixing biologics is not supported and increases risk without proven benefit.