The TrialSite Network includes many thousands of Hidradenitis Suppurativa patients eager for greater focus and investment, research, and breakthrough therapies for this debilitating disease impacting approximately 3.3 million in the United States. We have recently received requests from some HS patients asking about heart failure and Humira, and if there are any links. Only a rigorous scientific study could conclusively answer this question. However, we sought, upon request, to offer a basic literature review. It is by no means conclusive and, of course, any specific patient should work with their physician and always be ready to consider a second opinion—your health is everything!

Adalimumab is a TNF inhibitor along with other therapies, such as infliximab (Remicade), certolizumab pegol (Cimzia), golimumab (Simponi), etanercept (Enbrel), and others. In this review, we seek to identify specific research that connected or correlated any of these drugs with heart failure reports.

Adalimumab et al

Sold under the brand name Humira, this medication is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis. Typically use is recommended to those who haven’t responded to other treatments. Adalimumab is a disease-modifying antirheumatic drug and monoclonal antibody that works by inactivating tumor necrosis factor-alpha (TNFα). In this research, we centered on adalimumab and other TNF inhibitors for any material evidence of heart failure risks. Again, individuals reported to us that they were taking Adalimumab.

Manufacturer Acknowledges Potential Side Effect of Heart Failure

Among many side effects reported by the manufacturer, heart failure is included—just see their website. Manufacturer AbbVie  includes heart failure as a potential side effect although, based on a literature review, it would appear to be a rare occurrence. AbbVie itself acknowledges the risks of heart failure associated with Humira in a press release, announcing that they would present new data for upadacitinib and Humira at the 2018 ACR/ARHP Annual Meeting. 

Brief Review

AbbVie itself has shared Humira may have side effects including heart failure.

American Heart Association

The American Heart Association published a Scientific Statement titled Drugs That May Cause or Exacerbate Heart Failure. In this report, the authors’ referred to incidents of heart failure associated with tumor necrosis factor-α inhibitors, including adalimumab (Humira) for rheumatoid arthritis and Crohn’s disease patients. It was noted that this class of medication in post-marketing data point to some association with new-onset or worsening heart failure (HF). We look at the evidence from the American Heart Association report. First, they referred to the ATTACH trial (Anti-TNF Alpha Therapy Against CHF), where higher rates of heart failure-related hospitalization or death were noted in the patients with NHYA class III or IV heart failure receiving infliximab 10 mg/kg compared with the 5-mg/kg dose (HR, 2.84; 95% CI, 1.01-7.97).

Yale Research

In 2013, Yale researchers Ritesh Kohli and Karim Namek authored a report on Adalimumab (Humira)-induced acute lung injury, and in the “Background” section, they introduce that “the known secondary effects related with adalimumab included congestive heart failure.

Dr. JJ Cush, University of Texas Southwestern Medical School

JJ Cush, MD, of Rheumatology and Clinical Immunology, Presbyterian Hospital of Dallas, Clinical Professor of Internal Medicine, and The University of Texas Southwestern Medical School, Dallas, Texas, reports in Unusual Toxicities With TNF Inhibition: Heart Failure and Drug-Induced Lupus that “Serious and unexpected adverse events, such as heart failure and drug-induced lupus, have been reported in patients receiving TNF inhibitor therapy. These events generally are easily recognizable, although they cannot be predicted nor avoided, other than by drug avoidance altogether. Many patients have great benefit from anti-TNF therapies. Their intelligent use requires a firm understanding of these rare toxicities, so as to minimize the morbidity associated with their uncommon occurrence.”

Dr. Cush based these observations on the following clinical trials: RENAISSANCE, RECOVER and ATTACH programs. It should be noted the TNF inhibitors used were not adalimumab and that the patients did not have HS.

Dr. Cush weighed in again in a recent RheumNow report on tnf inhibition and heart failure. Cush reported that “The product label for marketed TNF inhibitors state, under warnings, that congestive heart failure “worsening or new onset” may occur. The label also guides that in certain studies, a higher rate of serious congestive heart failure-related adverse reactions was observed with TNFi use, and to “exercise caution when using TNFi in patients who have heart failure and monitor them carefully.”

Earlier Probe in Germany

Back in 2001, C. Antoni J. Braun, Department of Medicine, University Erlangen-Nuremberg, Erlangen, Germany authored Side Effects of Anti-TNF Therapy: The Current Knowledge where he probes the potential side effects early on in the trajectory of this class of treatment. He noted in the introduction that after the first wave of anti-TNF treatment, seven (7) adverse events materialized as a “special concern for patients treated with anti-TNF therapy,” including congestive heart failure.

Duke & FDA Authored Case Reports on TNF Antagonist Risk of Heart Failure

Another team in 2003 noted when it came to TNF antagonists Etanercept and infliximab that “clinicians should be aware that heart failure may occur in patients receiving TNF antagonists.” 

Brigham and Women’s Hospital Finds Risks with Elderly RA patients

Forward to 2008, a study authored by Brigham and Women’s Hospital found that TNFAs may increase the risk of both first hospitalization and exacerbation of heart failure in elderly patients with rheumatoid arthritis. The authors pointed out that larger, more detailed studies were needed to confirm their findings.

Conclusion

Based on a review of many dozens of studies, reports, and academic articles, it would appear that heart failure represents a risk associated with TNF Inhibitors, including adalimumab (Humira), etanercept, (Enbrel), infliximab (Remicade), and others. It would appear that these risks are fairly rare, but we couldn’t find an aggregate meta analyses pinpointing actual quantitative aspects—such as probabilities of occurrence. But for those TrialSite News engagements that had specific questions about Humira, the manufacturer includes the potential risk of heart failure in their labels and reports. Humira is the world’s best selling drug and obviously helps a large number of patients with no reports of heart failure, so from one perspective, it must be a very low risk probability. On the other hand, there doesn’t seem to be any readily available information that guides the patient and researchers as to what groups may face greater risks.

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