What are the considerations for adding apremilast to a treatment regimen for a patient with long-term use of Simponi Aria (golimumab)?

Adding Apremilast to Long-Term Simponi Aria (Golimumab) Therapy

Direct Recommendation

Apremilast can be safely added to ongoing Simponi Aria (golimumab) therapy for patients with psoriatic arthritis who have not achieved adequate response to the TNF inhibitor alone, with combination therapy demonstrating a favorable safety profile and potential for improved efficacy. 1, 2

Evidence-Based Rationale

Guideline Perspective on Combination Therapy

The 2018 ACR/NPF guidelines address combination strategies for psoriatic arthritis, though they generally favor switching over adding therapies. However, the guidelines specifically note that adding apremilast to current therapy is conditionally recommended over switching to apremilast monotherapy when patients have demonstrated partial response to their current treatment. 3 This provides direct guideline support for the combination approach when golimumab (a TNF inhibitor) has shown some benefit but inadequate control.

Safety Profile of Combination Therapy

The combination of apremilast with biologic agents, including TNF inhibitors like golimumab, has been demonstrated to be safe in clinical practice. 1, 2

Key safety findings include:

• In a retrospective study of 22 patients receiving apremilast added to various biologics, only 6 patients (27%) developed side effects, and none required discontinuation of therapy. 1
• A systematic review of 172 patients across 19 studies found only one serious adverse event (hospitalization for weight loss), with most adverse events being mild and gastrointestinal. 2
• No differences in adverse event rates were observed between apremilast monotherapy and combination therapy with biologics. 2

Monitoring Requirements for Combination Therapy

No routine laboratory monitoring is required when adding apremilast to golimumab, which simplifies the management burden. 4 However, specific clinical monitoring is essential:

• Monitor body weight at each visit, as weight loss exceeding 5% from baseline may necessitate discontinuing apremilast (occurs in approximately 12% of patients). 4
• Screen for depression before initiating apremilast and monitor at each visit, as depression occurs in approximately 1% of patients. 4
• Assess for gastrointestinal symptoms, particularly during the first 2 weeks when diarrhea and nausea occur in 70-80% of patients, though 75-80% are mild and 60-65% resolve within the first month. 4

Efficacy Considerations

While the evidence is primarily retrospective, combination therapy appears beneficial for appropriately selected patients:

• Only 2 patients out of 172 across multiple studies discontinued combination therapy due to lack of efficacy. 2
• Patients with partial response to TNF inhibitors may achieve better disease control with the addition of apremilast's complementary mechanism (PDE4 inhibition). 1, 5

Clinical Decision Algorithm

Consider adding apremilast to ongoing Simponi Aria when:

1. The patient has shown partial improvement in joint symptoms with golimumab but has not achieved treatment targets (remission or low disease activity). 3, 6
2. The patient has persistent skin manifestations despite adequate joint control with the TNF inhibitor. 1, 2
3. The patient prefers oral therapy as an add-on rather than switching to a different injectable biologic. 3
4. The patient has no contraindications to apremilast (severe renal impairment with CrCl <30 mL/min requires dose reduction to 30 mg once daily). 4

Avoid combination therapy when:

• The patient has achieved complete remission on golimumab alone, as there is no evidence supporting intensification in this scenario. 6
• The patient has significant depression or history of suicidal ideation, as apremilast carries a depression risk. 4
• The patient is unable to tolerate gastrointestinal side effects, which are common during apremilast initiation. 4, 7

Common Pitfalls to Avoid

Do not order routine laboratory monitoring "just to be safe" when adding apremilast—this adds unnecessary cost and patient burden without clinical benefit, as apremilast does not cause bone marrow suppression or hepatotoxicity. 4

Do not discontinue golimumab when adding apremilast if the TNF inhibitor has shown partial benefit, as the combination approach leverages complementary mechanisms of action. 1, 2

Do not neglect weight monitoring—this is the single most important objective parameter to track, as significant weight loss may require apremilast discontinuation. 4

Counsel patients extensively about gastrointestinal side effects before initiation, emphasizing that these are typically mild and resolve within the first month in most cases. 4, 7 This prevents premature discontinuation during the titration period.

Alternative Consideration

If the patient has failed golimumab entirely (no response), the 2018 ACR/NPF guidelines recommend switching to a different TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor rather than adding apremilast, as these biologics demonstrate superior efficacy compared to apremilast monotherapy. 3 However, if switching is not feasible due to patient preference for oral therapy, insurance barriers, or contraindications to other biologics, adding apremilast remains a reasonable option. 1, 2