Should Apremilast Be Suspended During Clinically Significant Infection?
No, apremilast does not need to be routinely suspended during active infections, unlike biologic DMARDs, because it does not cause immunosuppression or increase serious infection risk. This represents a key clinical advantage of apremilast over biologics in patients with infection concerns.
Evidence-Based Rationale
Apremilast's Favorable Infection Profile
Apremilast is specifically recommended for patients with recurrent or serious infections where biologics may be contraindicated. The ACR/NPF guidelines explicitly state that apremilast may be considered in patients with "contraindications to TNFi biologics, including recurrent infections, congestive heart failure, or demyelinating disease" 1.
The EULAR guidelines similarly position apremilast for "patients with comorbidities or a history of infections contraindicating any bDMARD" 1.
Real-world evidence demonstrates apremilast's safety during active infection periods. A study of 48 psoriasis patients during the COVID-19 pandemic showed no patients stopped apremilast treatment due to infection concerns, with the drug maintaining its safety profile throughout the outbreak period 2.
Perioperative Management Supports Continuation
The 2022 ACR/AAHKS perioperative guidelines recommend continuing apremilast through elective surgery without interruption, unlike biologics which must be withheld 1. This recommendation reflects apremilast's lack of immunosuppressive effects that would increase surgical site infection risk.
The guideline explicitly states: "continuing the usual dosing of...apremilast" is conditionally recommended for patients undergoing total joint arthroplasty 1.
Safety Data from Long-Term Studies
Serious opportunistic infections with apremilast are exceptionally rare, with an exposure-adjusted incidence rate of 0.0 per 100 patient-years over 3 years of treatment in pooled PALACE trial data 3.
Among 841 psoriasis patients with serious baseline comorbidities (including chronic infections) treated with apremilast, no infection reactivations or worsening were documented 4.
Clinical Decision Algorithm
When to Continue Apremilast:
- Mild to moderate infections (upper respiratory infections, uncomplicated UTIs, cellulitis): Continue apremilast without interruption 2, 4
- Perioperative period: Continue through surgery 1
- Patients with history of recurrent infections: Apremilast is actually preferred over biologics in this population 1
When to Consider Temporary Suspension:
- Severe systemic infections requiring hospitalization: Use clinical judgment, though evidence does not mandate suspension
- Sepsis or life-threatening infection: Temporary hold may be prudent until clinical stability, though this is based on general medical principles rather than specific apremilast data
Key Mechanistic Distinction
Apremilast is a PDE4 inhibitor, not an immunosuppressant. Unlike TNF inhibitors, IL-17 inhibitors, or IL-12/23 inhibitors that directly suppress immune function, apremilast modulates inflammatory pathways without causing clinically significant immunosuppression 1. This fundamental difference explains why infection management differs dramatically from biologics.
Common Pitfalls to Avoid
Do not treat apremilast like a biologic DMARD by reflexively holding it during infections—this is unnecessary and may lead to disease flare 1.
Do not confuse apremilast's gastrointestinal side effects with infection-related symptoms. Diarrhea occurs in 70-80% of patients within the first 2 weeks but is self-limited and not infection-related 5.
Do not withhold apremilast in elderly patients with infections unless there are concerns about dehydration from concurrent GI symptoms, which is the actual risk in this population 6, 5.
Practical Management
For patients on apremilast who develop infection:
- Continue apremilast at standard dosing (30 mg twice daily) 1, 2
- Treat the infection appropriately with antimicrobials as indicated
- Monitor for dehydration if GI symptoms are present, particularly in elderly patients 6
- Reassess only if the patient develops sepsis or requires ICU-level care
This approach contrasts sharply with biologic DMARDs, where guidelines mandate withholding therapy during active infections and timing surgery after drug washout periods 1.