IL Inhibitors Therapy in Rheumatic Diseases and the Risk of Malignancies: Systematic Review and Meta-Analysis of Rare Harmful Effects in Randomized Controlled Trials

Jawad Bilal¹, Irbaz Bin Riaz², Adam Berlinberg³, Abdullah Alhifany⁴, Gilbert Ortega⁵ and Warda Faridi⁶, ¹University of Arizona, Tucson, AZ, ²Mayo Clinic, Richestor, MN, ³Department of Internal Medicine, University of Arizona, Tucson, AZ, ⁴Department of Pharmacy, University of Arizona, Tucson, AZ, ⁵Internal Medicine, University of Arizona, Tucson, Tucson, AZ, ⁶Department of Hematology/Oncology, University of Arizona, Tucson, AZ

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: interleukins (IL), Malignancy and rheumatic disease

Session Information

Date: Sunday, October 21, 2018

Title: Epidemiology and Public Health Poster I: Rheumatoid Arthritis

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Tumor necrosis factor alpha (TNFα) inhibitor therapy in patients with rheumatologic disorders is well known to increase the risk of malignancy. While the individual trials report these incident side effects with Interleukin (IL) inhibitor therapy, the subject has not been systematically investigated.

Objective:

To investigate the risk of malignancies in patients with rheumatic diseases treated with interleukin (IL) inhibitor therapies (Anakinra, brodalumab, canakinumab, secukinumab, tocilizumab, olokizumab, ixekizumab, ustekinumab, clazakizumab, and rilanocept).

Methods:

Medline via Pubmed, Embase, conference proceedings from ASCO, AACR and ACR and reference lists from published systematic reviews related to rheumatologic diseases and interleukin inhibitors for were searched for RCTs using PICOS strategy. We extracted the incident data for malignancies. We conducted a fixed-effect meta-analysis via calculating a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) using STATA software version 14 (Stata Corp., College Station, Texas, USA). Heterogeneity was assessed using Q-statistic and quantified using I²statistic.

Results:

After screening 881 studies, 16841 patients from 38 eligible studies were analyzed. We found no significant difference between patients who received IL-inhibitors or placebo in terms of the risk of malignancies (OR 1.07, 95% CI 0.708-1.63; I²= 9.9%, P = 0.32). We conducted a sensitivity analysis to examine the risk of malignancies based on individual IL-inhibitors. We found no significant difference in the occurrence of malignancies in patients who received anakinra, Ixekizumab, Rilanocept, Secukinumab, Tociliuzumab or Ustekinumab versus placebo (OR 0.20, 95% CI 0.06-0.66; I²= 0%, P = 0.97), (OR 1.28, 95% CI 0.30-5.5; I²= 4.9%, P = 0.35), (OR 2.18, 95% CI 0.22-21.23; I²= 0%, P = 0.75), (OR 2.43, 95% CI 0.71-8.27; I²= 0%, P = 0.98), and (OR 1.46, 95% CI 0.72-2.97; I²= 44%, P = 0.13), and (OR 2.14, 95% CI 0.25-18.37; I² = 0%, P = 0.67) respectively.

Conclusion:

IL inhibitors therapies appear safe with regards to risk of malignancies for a follow up duration of up to 52 weeks. Long term data is required from cancer survivors to further ensure the safety of IL inhibitor therapies.

Disclosure: J. Bilal, None; I. B. Riaz, None; A. Berlinberg, None; A. Alhifany, None; G. Ortega, None; W. Faridi, None.

To cite this abstract in AMA style:

Bilal J, Riaz IB, Berlinberg A, Alhifany A, Ortega G, Faridi W. IL Inhibitors Therapy in Rheumatic Diseases and the Risk of Malignancies: Systematic Review and Meta-Analysis of Rare Harmful Effects in Randomized Controlled Trials [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/il-inhibitors-therapy-in-rheumatic-diseases-and-the-risk-of-malignancies-systematic-review-and-meta-analysis-of-rare-harmful-effects-in-randomized-controlled-trials/. Accessed .

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