How to manage moderate to severe Crohn's (Crohn's disease) disease involving the ileum and colon in a patient who developed multiple myeloma while on anti-Tumor Necrosis Factor (anti-TNF) therapy?

From the Guidelines

For a patient with moderate to severe Crohn's disease involving the ileum and colon who has developed multiple myeloma while on an anti-TNF agent, I recommend discontinuing the anti-TNF therapy and transitioning to ustekinumab (Stelara) as the most appropriate management strategy. This approach is based on the latest evidence from high-quality studies, including those published in 2019 1, which suggest that ustekinumab is a viable option for patients with moderate to severe Crohn's disease who have failed or are intolerant to anti-TNF therapy.

Rationale for Ustekinumab

Ustekinumab, an IL-12/23 inhibitor, has a different mechanism of action than anti-TNF agents and generally poses less immunosuppressive risk in the setting of malignancy. The Canadian Association of Gastroenterology clinical practice guideline for the management of luminal Crohn's disease recommends ustekinumab for patients with moderate to severe Crohn's disease who fail to achieve complete remission with any of corticosteroids, thiopurines, methotrexate, or anti-TNF therapy 1. Additionally, a systematic review and meta-analysis of four randomized controlled trials (RCTs) found that ustekinumab was significantly better than placebo for the outcome of failure to achieve remission in adult patients with moderate to severe Crohn's disease 1.

Treatment Protocol

The recommended treatment protocol for ustekinumab in this setting includes an intravenous induction dose of approximately 6 mg/kg (typically 520 mg for most adults), followed by 90 mg subcutaneous injections every 8 weeks for maintenance. Close coordination with both gastroenterology and hematology-oncology is essential, as the multiple myeloma treatment (likely involving proteasome inhibitors, immunomodulators, or monoclonal antibodies) may affect Crohn's management.

Monitoring and Adjunctive Therapy

Regular monitoring with blood work, including inflammatory markers (CRP, ESR), complete blood counts, and liver function tests every 1-3 months, is necessary to assess the patient's response to therapy. Endoscopic reassessment of Crohn's activity should be performed within 6 months of therapy change. Nutritional support and symptom management with antidiarrheals or antispasmodics may be needed as adjunctive therapy during this transition period.

Key Considerations

The development of multiple myeloma in a patient with Crohn's disease on anti-TNF therapy necessitates a careful reassessment of the treatment strategy to minimize the risk of exacerbating the malignancy. Ustekinumab, with its distinct mechanism of action and relatively lower immunosuppressive risk, offers a promising alternative for managing moderate to severe Crohn's disease in this context. By prioritizing the patient's morbidity, mortality, and quality of life, this approach aims to optimize outcomes in a complex and challenging clinical scenario.

From the FDA Drug Label

The improvements in the components of the ASAS response and other measures of disease activity were higher in XELJANZ 5 mg twice daily compared to placebo as shown in Table 18 XELJANZ is indicated for patients who have an inadequate response or intolerance to one or more TNF blockers [see Indications and Usage (1)]. A total of 52%, 73% and 72% of patients had previously failed or were intolerant to TNF blockers (51% in Study UC-1 and 52% in Study UC-II), corticosteroids (75% in Study UC-I and 71% in Study UC-II), and/or immunosuppressants (74% in Study UC-I and 70% in Study UC-II), respectively

Management of Moderate to Severe Crohn's Disease

• The patient developed multiple myeloma while on anti-TNF therapy, and there is no direct information in the label to guide the management of Crohn's disease in this specific situation.
• However, the label does indicate that XELJANZ is used for patients with an inadequate response or intolerance to one or more TNF blockers.
• No conclusion can be drawn on how to manage moderate to severe Crohn's disease involving the ileum and colon in a patient who developed multiple myeloma while on anti-TNF therapy based on the provided label information 2.

From the Research

Managing Moderate to Severe Crohn's Disease

• In patients with moderate to severe Crohn's disease involving the ileum and colon, azathioprine (AZA) and 6-mercaptopurine are therapeutic options 3.
• AZA has been shown to maintain remission and reduce corticosteroid use in patients with Crohn's disease 3.
• However, AZA has a complex metabolism and potential for adverse events, and routine thiopurine methyltransferase testing before initiation of AZA is mandatory to avoid potentially life-threatening myelotoxicity 3.

Anti-TNF Therapy

• Anti-TNF therapy was approved for use in Crohn's disease in 1998 and has changed the paradigm of treatment, leading to improved rates of response and remission in patients 4.
• However, a significant proportion of patients lose response to anti-TNF therapy over time 5, 6.
• Introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy can recapture response, even if the patient has previously failed thiopurine therapy 5, 6.

Managing Patients with Multiple Myeloma on Anti-TNF Therapy

• There is no direct evidence on managing moderate to severe Crohn's disease in patients who developed multiple myeloma while on anti-TNF therapy.
• However, it is known that anti-TNF therapy can increase the risk of certain cancers, including lymphoma and skin cancer 4, 7.
• In patients with Crohn's disease who develop multiple myeloma, the treatment approach may need to be individualized, taking into account the risks and benefits of continuing or discontinuing anti-TNF therapy, as well as the potential need for alternative therapies such as thiopurines or other immunomodulators 3, 5, 6.