Is it safe to use clindamycin, doxycycline, or rifampicin concurrently with adalimumab in a patient with intermittent hidradenitis suppurativa flares?

Safety of Combining Antibiotics with Adalimumab in Hidradenitis Suppurativa

Yes, clindamycin, doxycycline, and rifampicin can be safely combined with adalimumab for hidradenitis suppurativa, and the combination of clindamycin-rifampicin with adalimumab is actually more effective than adalimumab monotherapy. 1

Evidence for Safety and Enhanced Efficacy

Combining adalimumab with clindamycin 300 mg twice daily plus rifampicin 300-600 mg daily demonstrates superior clinical effectiveness compared to adalimumab alone, with significantly greater IHS4 improvement (-20 vs. -9, p<0.001), higher IHS4-55 response rates (74% vs. 36%, p=0.002), and better draining tunnel reduction (-4 vs. -2, p<0.001) at 12 weeks. 1

The 2025 North American Clinical Practice Guidelines explicitly support this combination approach, recommending clindamycin-rifampicin as standard therapy for moderate disease that can be used alongside biologics. 2, 3

Specific Antibiotic-Adalimumab Combinations

Clindamycin + Rifampicin with Adalimumab

• This is the preferred combination when initiating adalimumab therapy, particularly for patients with draining tunnels or moderate-to-severe disease. 1
• The antibiotic combination should be started concurrently with adalimumab loading (160 mg week 0,80 mg week 2, then 40 mg weekly) and continued for 10-12 weeks. 3, 1
• This regimen addresses a critical limitation of adalimumab monotherapy by significantly reducing draining tunnels, which respond poorly to adalimumab alone. 1

Doxycycline with Adalimumab

• Doxycycline 100 mg once or twice daily can be safely used with adalimumab, though it was evaluated in the PIONEER trials and showed no independent benefit when combined with adalimumab. 3
• Doxycycline is less effective than clindamycin-rifampicin for moderate-to-severe disease (only 30% abscess reduction as monotherapy). 3
• Consider doxycycline with adalimumab primarily in patients who cannot tolerate clindamycin-rifampicin or in special populations such as HIV-positive patients where it provides added prophylactic benefit against bacterial STIs. 2

Safety Profile of Long-Term Combination Therapy

The safety concerns with clindamycin-rifampicin cluster within the first 10 weeks of treatment, and therapy can be continued beyond this period if clinically necessary. 4

Rifampicin Safety Considerations

• The risk of rifampicin-induced liver injury is highest in the first 6 weeks of treatment. 4
• Hepatic enzyme induction is complete after approximately 2 weeks and reduces clindamycin blood levels by about 90%, but this does not appear to compromise clinical efficacy in HS. 4
• Interstitial nephritis is primarily observed during intermittent (not continuous) rifampicin treatment. 4

Clindamycin Safety Considerations

• Community-acquired Clostridium difficile infection (CA-CDI) is a concern with clindamycin, though meta-analyses have not stratified risk by treatment duration. 4
• Diarrhea is a frequent side effect of the clindamycin-rifampicin combination, occurring in a substantial proportion of patients. 5
• Combining topical clindamycin with benzoyl peroxide or chlorhexidine reduces Staphylococcus aureus resistance risk, though this applies to topical rather than systemic use. 3

Treatment Algorithm for Intermittent Flares

For a patient with intermittent HS flares already on adalimumab maintenance:

1. During an acute flare, initiate clindamycin 300 mg twice daily plus rifampicin 300-600 mg daily for 10-12 weeks while continuing adalimumab 40 mg weekly. 3, 1

2. Add intralesional triamcinolone 10 mg/mL to acutely inflamed nodules for rapid symptom relief within 24 hours. 3

3. After completing the 10-12 week antibiotic course, consider a treatment break from antibiotics to assess ongoing need and limit antimicrobial resistance, while maintaining adalimumab. 3, 4

4. If flares recur after stopping antibiotics, the clindamycin-rifampicin combination can be repeated intermittently as needed, as the safety risks cluster in the first 10 weeks and do not appear to increase with repeated courses. 4, 5

Critical Pitfalls to Avoid

• Do not use doxycycline as first-line antibiotic with adalimumab for moderate-to-severe disease with abscesses or draining tunnels, as it has minimal effect on these lesions. 3

• Do not continue antibiotics indefinitely without treatment breaks, as this increases antimicrobial resistance risk without proven additional benefit beyond 10-12 weeks. 3, 4

• Monitor for diarrhea when using clindamycin-rifampicin, as this is a common side effect that may require discontinuation. 5

• Be aware of drug interactions with rifampicin, particularly in patients on hormonal contraceptives, anticoagulants, or other medications metabolized by hepatic P450 3A4 enzymes. 4