What are alternative treatment options for a patient with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis who has tried Tofacitinib (Xeljanz)?

Alternative Treatment Options After Tofacitinib Failure

For patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis who have failed tofacitinib, switch to a TNF inhibitor as the preferred first-line alternative, followed by IL-17 inhibitors as second-line options. 1, 2

Disease-Specific Treatment Algorithms

For Psoriatic Arthritis (PsA)

First-Tier Alternative: TNF Inhibitors

• Switch to adalimumab, etanercept, infliximab, golimumab, or certolizumab as these have the most extensive long-term safety data and proven efficacy in slowing radiographic progression 2
• TNF inhibitors are conditionally recommended over IL-17 inhibitors, IL-12/23 inhibitors, abatacept, and other JAK inhibitors based on ACR/NPF guidelines 1

Second-Tier Alternative: IL-17 Inhibitors

• Switch to secukinumab (150-300 mg subcutaneously) or ixekizumab if the patient has severe psoriasis requiring aggressive skin disease control 1, 2
• IL-17 inhibitors are conditionally recommended over IL-12/23 inhibitors for patients prioritizing skin clearance 1
• Critical caveat: Avoid IL-17 inhibitors if the patient has concomitant inflammatory bowel disease, as they may worsen IBD 1

Third-Tier Alternative: IL-12/23 Inhibitors

• Switch to ustekinumab if the patient prefers less frequent dosing (every 12 weeks after loading) 1, 2
• Ustekinumab is particularly appropriate for patients with concomitant inflammatory bowel disease 1

Fourth-Tier Alternative: Abatacept

• Consider abatacept specifically for patients with recurrent or serious infections where TNF inhibitors and tofacitinib may be contraindicated 1, 2
• Abatacept is conditionally recommended for patients preferring IV administration 1

For Ankylosing Spondylitis (AS)

First-Tier Alternative: TNF Inhibitors

• TNF inhibitors are strongly recommended as the preferred biologic therapy for AS patients who have failed NSAIDs and tofacitinib 3
• This represents the highest strength of recommendation in the AS treatment algorithm 3

Second-Tier Alternative: IL-17 Inhibitors

• Switch to secukinumab or ixekizumab as strongly recommended alternatives to TNF inhibitors 3
• IL-17 inhibitors are conditionally recommended to be used after TNF inhibitors rather than as first-line biologics 3

Critical Safety Consideration for AS

• Tofacitinib is only conditionally recommended in AS when TNF inhibitors and IL-17 inhibitors are not available or contraindicated 3
• For AS patients with coexisting ulcerative colitis, tofacitinib would have been preferred over IL-17 inhibitors, but since the patient has already failed tofacitinib, TNF inhibitors become the optimal choice 3

Patient-Specific Selection Criteria

If the patient has severe psoriasis:

• Prioritize IL-17 inhibitors (secukinumab, ixekizumab) or IL-12/23 inhibitors (ustekinumab) over TNF inhibitors 1

If the patient has inflammatory bowel disease:

• Use TNF inhibitors or ustekinumab; absolutely avoid IL-17 inhibitors 1

If the patient has recurrent or serious infections:

• Consider abatacept over TNF inhibitors 1, 2
• Avoid returning to any JAK inhibitor including tofacitinib 1

If the patient has history of recurrent Candida infections:

• Avoid IL-17 inhibitors; TNF inhibitors or abatacept are preferred 1

If the patient prefers less frequent dosing:

• Choose IL-12/23 inhibitors (ustekinumab every 12 weeks) over other options 1, 2

If the patient prefers IV administration:

• Consider abatacept or infliximab 1, 4

Critical Safety Considerations Based on Cardiovascular Risk

For patients ≥65 years of age or long-time current/past smokers:

• The ORAL Surveillance trial demonstrated increased rates of major adverse cardiovascular events (MACE), malignancies, and venous thromboembolism with tofacitinib versus TNF inhibitors in this population 5
• Switching from tofacitinib to a TNF inhibitor is particularly important for these high-risk patients 5

For patients with history of atherosclerotic cardiovascular disease:

• TNF inhibitors showed lower MACE risk compared to tofacitinib in post-hoc analyses 5
• This makes TNF inhibitors the strongly preferred alternative after tofacitinib failure in this population 5

Important Treatment Transition Principles

Combination Therapy Considerations:

• Continue methotrexate during the transition to IL-17 or IL-12/23 inhibitors to allow the new therapy time to work 1
• For psoriatic arthritis, combine the new biologic with methotrexate, sulfasalazine, or leflunomide as appropriate 6

Critical Safety Warning:

• Never combine two biologic agents simultaneously due to unpredictable immune dysregulation and lack of safety data 2
• Do not use tocilizumab, etanercept, adalimumab, infliximab, rituximab, abatacept, anakinra, certolizumab, golimumab, ustekinumab, secukinumab, vedolizumab, or ixekizumab concurrently with another biologic 6

Insurance Coverage Considerations

• Most insurance formularies require TNF inhibitor trials before approving IL-17 or IL-12/23 inhibitors, which aligns with guideline recommendations 2
• This step-therapy approach supports the evidence-based treatment algorithm presented above 2