Case Study Indicates IVIG May Counteract Adalimumab

The Center for Biosimilars Staff

Patients taking adalimumab along with intravenous immunoglobulin (IVIG) treatments to fortify their immune system may find that they experience declining efficacy from adalimumab in the wake of IVIG treatments.

According to a troubling case study presented at the 2017 Annual Meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI) in Atlanta, Georgia, on March 5, 2017, adalimumab (the generic biologic for Humira) was diminished in effect following IVIG. The patient, a 62-year-old woman with common variable immune deficiency (CVID), Crohn’s disease, and rheumatoid arthritis, was receiving adalimumab to alleviate joint pain, stiffness, and Crohn’s-related chronic diarrhea. She brought the issue of diminished efficacy to her physicians’ attention during a visit to her immunology clinic. “She stated that on the one week of the month when her adalimumab overlapped with her IVIG infusion, she experienced diminished relief of severe joint pain, stiffness, and diarrhea [that] resolved following her next dose of adalimumab,” study author Trisha Sharma, MD, a physician at the UCSD School of Medicine in San Diego, reported. Prior to beginning adalimumab therapy, the patient had received IVIG therapy over the course of the previous year.

Adalimumab, a biologic, has been approved by the FDA for treatment of rheumatoid arthritis, chronic plaque psoriasis, Crohn’s disease, psoriatic arthritis, and several other inflammatory conditions. The FDA classifies biologic drugs as those “composed of sugars, proteins, nucleic acids, or combinations of these substances” or “living entities such as cells and tissues.” They are isolated from natural sources, produced by biotechnological methods, and often can be used to treat conditions for which few or no other treatments are available. Biologics, and their follow-on biosimilars, often tend to be less likely to provoke inflammation in patients with inflammatory disorders, and are particularly interesting to immunologists, allergists, and asthmologists, whose patients already spend a great deal of their lives experiencing increased inflammation in various parts of their bodies.

Adalimumab is a humanized monoclonal antibody (mAb), which is less likely to be targeted by a sensitive immune system than other types of antibody therapies. However, in the above patient’s case, the IVIG therapy may have essentially caused her immune system to “attack” the adalimumab monoclonal antibodies immediately following the IVIG dose.

“When duration between administration of adalimumab and IVIG was increased, on follow-up the patient reported no improvement,” noted Dr Sharma, adding that the patient’s IgG trough levels prior to IVIG transfusions “remained at therapeutic levels” even with the change in administrative schedule. “We hypothesize that coadministration of adalimumab with IVIG may result in reduced therapeutic effect from the mAb [monoclonal antibody] therapy,” the researchers concluded, speculating that the problem could lie with “anti-idiotypic antibodies within the suprephysiologic IgG levels immediately following IV dosing.”

“Understanding the mechanism [of the interaction] will be increasingly important as mAb therapies are more widely administered,” the authors added. A similar phenomenon was noted in a separate study involving IVIG and Alzheimer’s patients, wherein the IVIG treatment may have diminished the neuroprotective effects of certain antibodies following dual treatment. In that study, the authors speculated that an Alzheimer’s disease-specific IVIG treatment “might be the last and best chance for IVIG treatment” to succeed in the context of treating Alzheimer’s disease. However, they warned that this option would have substantial financial, regulatory, and production-related obstacles.

This case study’s indication of the interaction between IVIG and adalimumab, a popular biologic treatment, serves to emphasize the need for additional biologic and biosimilar treatments for inflammatory conditions. In Europe, 2 biosimilars for adalimumab were recently recommended for approval to the European Medicines Agency (EMA)’s committee for medicinal products for human use. Those biosimilars, Amjevita and Solymbic, are the first of their kind recommended for approval in the European Union (EU), and both are stated to provided comparable treatment for the conditions treated by adalimumab. Amgen’s biosimilar, adalimumab-atto, was approved in the United States in late 2016 but was not approved to be interchangeable with adalimumab or to treat patients as young as are approved for adalimumab treatment. Although adalimumab-atto is now FDA-approved in a limited capacity, it is not being marketed in the United States due to a lawsuit filed by Humira’s manufacturer, Abbvie. Case studies like this one, wherein the patient’s experience with the biologic may be compromised due to concomitant treatments, demonstrate the importance of alternative treatments that may be more effective while continuing to provide symptom management in a manner similar to that of preceding drugs and biologics.