When can secukinumab (Stelara) be started in a patient currently on cyclosporine and methotrexate?

When to Start Secukinumab in Patients on Cyclosporine and Methotrexate

Secukinumab can be started immediately with direct switching from cyclosporine or methotrexate without requiring a washout period, though the safest approach is to discontinue both immunosuppressants before initiating secukinumab to minimize cumulative immunosuppression risks.

Evidence-Based Switching Strategy

Direct Switch from Cyclosporine

• A prospective phase IV study demonstrated that secukinumab can be safely initiated with direct switching from cyclosporine in patients with inadequate response, with 82.4% achieving PASI 75 at week 16 and no serious adverse events reported 1.
• Early improvements were observed with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4 after direct switch 1.
• The study showed a favorable safety profile with no new or unexpected safety signals when switching directly from cyclosporine 1.

Combination Therapy Considerations

• The AAD-NPF guidelines indicate that ustekinumab (an IL-12/23 inhibitor similar to secukinumab's IL-17 mechanism) may be combined with cyclosporine, though the long-term safety is unknown and there is limited data from case reports 2.
• The British Association of Dermatologists notes that combining methotrexate with cyclosporine raises additional safety concerns, particularly increased immunosuppressive effects, and co-therapy is not recommended routinely 2.
• The most common scenario for using both drugs is during transitioning from one therapy to the next 2.

Recommended Approach: Sequential Transition

Step 1: Discontinue Current Immunosuppressants

• Stop cyclosporine first as it has a shorter half-life and more concerning drug interactions with biologics 2.
• Taper or discontinue methotrexate depending on disease severity and risk of flare 2.
• The British guidelines support short-term overlap when transitioning between treatments to prevent psoriasis flares, but blood monitoring should be performed more frequently 2.

Step 2: Timing of Secukinumab Initiation

• Secukinumab can be started immediately after discontinuing cyclosporine and methotrexate without a mandatory washout period based on the direct switch study showing safety and efficacy 1.
• If concerned about disease flare during transition, a brief overlap (1-2 weeks) of methotrexate with secukinumab initiation may be considered, though this increases immunosuppression risk 2.
• For patients with severe disease at high risk of flare, consider starting secukinumab while tapering (rather than abruptly stopping) the conventional agents over 2-4 weeks 2.

Critical Safety Considerations

Infection Risk Monitoring

• Screen for latent tuberculosis before initiating secukinumab, as required by FDA labeling and guidelines 3.
• Complete blood count and metabolic profile should be obtained at baseline 3.
• The risk of tuberculosis reactivation with secukinumab is very low (EAIR 0.03 for psoriasis), with only 13 cases of LTBI reported as adverse events in 12,319 patients over 5 years 4.

Avoiding Triple Immunosuppression

• Never maintain all three agents (cyclosporine, methotrexate, and secukinumab) concurrently beyond a brief transition period, as combination immunosuppression significantly increases infection risk 2.
• The AAD-NPF guidelines state there is not enough evidence to recommend combination of biologics with other immunosuppressive therapies due to unknown risk of significant adverse events 2.

Common Pitfalls to Avoid

• Do not delay secukinumab initiation for prolonged washout periods unless there is active infection or other contraindication, as this unnecessarily prolongs inadequate disease control 1.
• Avoid combining cyclosporine with UVB or other phototherapy due to increased skin cancer risk, but this is not relevant when switching to secukinumab 2.
• Do not restart cyclosporine or methotrexate at full doses if secukinumab fails; reassess the clinical situation and consider alternative biologics 2.
• Monitor renal function if there was any impairment on cyclosporine, as this should improve after discontinuation 2.