Risk of Lymphoma Associated with Combination of Anti-Tumor Necrosis Factor and Immunomodulator Therapy for the Treatment of Crohn’s Disease: A Meta-Analysis.
Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE
Clin Gastroenterol and Hepatol. 2009;7:874-881. |
Summary:
This study examined the risk of non-Hodgkin’s lymphoma (NHL) from a select group of subjects with a single inflammatory disorder, Crohn’s Disease (CD) treated with a variety of Anti-TNFα agents [Infliximab (IFX), Adalimumab (ADA) and Certolizumab (CTZ)]. This meta-analysis included 8,905 patients with CD participating in 26 studies from across the world for an aggregate follow up of 21,718 pt-yrs. The primary parameter evaluated was rate of NHL, which was determined to be 3x greater than expected in the general U.S. population. Since 77% (10 of 13) of patients with CD developing NHL were receiving “combination” Anti-TNFα and Immunomodulator Rx and only 1 of the CD patients developing NHL was receiving ONLY Anti-TNFα treatment, it is a concern that combination not mono-Anti-TNFα therapy that carries the significant increased risk for NHL among CD pts.
Conclusions:
1. Use of Anti-TNFα drugs for the treatment of Crohn's’ disease is associated with an increased risk for NHL.
2. Absolute risk for NHL among these patients is:
a. 6.1 per 10,000 pt-yrs (NHL Meta-Analysis)
or 3x greater than the expected
b. 1.9 per 10,000 pt-yrs (NHL SEER rate)
3. The majority of pts with NHL were receiving BOTH Anti-TNFα and Immunomodulator Rx.
a. 10 of 13 (77%) reported NHL patients were on both Anti-TNFα & Immunomodulator Rx.
b. 2 of 13 (15%) reported NHL patients were on Anti-TNFα, but Immunomodulator Rx use was not reported.
c. 1 of 13 (8%) reported NHL patients were on ONLY Anti-TNFα.
4. Overall risk for NHL for Crohn’s patients given both Anti-TNFα and an Immunomodulator Rx seems to be greater for men and patients older than 55 yrs.
5. At least 4 patients were discovered to have NHL after the 1st infusion of Anti-TNFα. This might suggest that the effect of even one dose may be significant to increase lymphoma risk or alternatively that a significant number of NHL pts in this report were just pre-clinical.
Adalimumab Safety and Mortality Rates from Global Clinical Trials of Six Immune-Mediated Inflammatory Diseases
Burmester GR, Mease P, Dijkmas BAC, Gordon K, Lovell D, Panaccione R, Perez J, Pangan AL
Ann Rheum Dis. Ann Rheum Dis. 2009;68:1863-9. Epub 2009 Jan 15 |
Summary:
This study examined the specific risk and safety associated with a single Anti-TNFα, Adalimumab (ADA), Rx for treatment of a broad group of inflammatory disorders [ Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), Juvenile Idiopathic Arthritis (JIR), Psoriasis (Ps) and Crohn’s Disease (CD)]. The strength of this study is the evaluation of large cohort over a relatively long study period involving a single Anti-TNF agent (ADA) with potentially less antigenic properties that the first generation Anti-TNF agents. The study included 19,041 subjects included in controlled ADA studies of the treatment of 6 inflammatory disorders for a total of 18,284 pt-yrs.
Conclusion:
Based on 10 years of clinical trial experience across six inflammatory diseases, ADA has a stable safety profile and “acceptable” risk benefit ratio.
1. ↓Risk for Malignancy (all): SIR = 0.83
2. ↑Risk for Lymphoma in RA: SIR = 2.98
3. ↑Risk for TB: Note 62% extra-pulmonary in RA
4. ↑Risk for Opportunistic Infections: RA #1 Lung & CD #1 Abscess
5. ~Risk for Demyelinating disease: infrequent
6. ~Risk for Lupus Syndrome: infrequent |
