Givlaari normalized woman’s lab results but her AIP attacks continued
Celiac plexus block was able to decrease her pain significantly
Treatment with Givlaari (givosiran) normalized disease-related laboratory parameters in a 47-year-old woman with acute intermittent porphyria (AIP) but she continued to experience severe symptom attacks despite getting normal test results.
“We report a patient with AIP who experienced biochemical resolution of her [disease] with monthly [Givlaari] injections yet continued to experience AIP symptoms,” researchers wrote.
Her case was described in a report, “Recurrent symptoms of acute intermittent porphyria after biochemical normalization with givosiran — An ongoing clinical conundrum,” published in JIMD Reports.
Buildup of porphyrins thought to drive symptom attacks
AIP is marked by increased levels of the protein ALAS1. This leads to an abnormal buildup of compounds called porphyrins, such as aminolevulinic acid (ALA) and porphobilinogen (PBG). This buildup is thought to be the main driver of symptom attacks in people with AIP, and measuring their levels in the urine is commonly used to track disease severity.
Givlaari was approved in the U.S. to treat AIP and other forms of acute hepatic porphyria in 2019. The therapy is given once monthly via subcutaneous (under-the-skin) injection, and it works by lowering the levels of ALAS1 protein, thereby preventing the abnormal accumulation of porphyrins.
In the report, a trio of researchers in the U.S. document the case of a woman who was diagnosed with AIP at age 34, and was experiencing AIP attacks nearly once a month at age 47 when she was evaluated at the researchers’ clinic. Her symptoms included acute abdominal pain, stabbing sensations in her limbs, fatigue, nausea, vomiting, and skin damage in response to sunlight (photosensitivity).
Her attacks usually occurred around the time of ovulation, which the researchers noted is common for women with AIP. She had been managing her condition mainly with symptomatic treatments (e.g., narcotics for pain relief).
Tests of her urine showed markedly elevated levels of ALA, PBG, and total porphyrins.
The patient was then started on Givlaari, which she tolerated well, and after three months, her laboratory tests showed porphyrin levels had decreased to within the normal range. Porphyrin levels remained low out to at least a year on Givlaari.
This case highlights the importance of careful ongoing clinical observations of responses to medications and the possible benefits of implementing other treatments, like splanchnic nerve blocks as in our patient, to optimize patient care.
Despite normalization of porphyrin levels, however, the patient continued to experience acute attacks of AIP symptoms nearly every month, usually at the same point in her menstrual cycle. Some of these attacks were severe enough for her to be admitted to the hospital. During these visits, she was unable to eat due to severe abdominal pain and vomiting.
“Our patient responded promptly to [Givlaari] with normalization of levels of urinary ALA, PBG, and porphyrins, but continued to experience frequent attacks of abdominal pain and other symptoms that she interpreted as continuing typical acute porphyric attacks, albeit with a lower frequency than prior to the start of [Givlaari],” the researchers wrote.
The patient said her symptoms normally eased in the first few days after each monthly Givlaari injection. Nevertheless, she was still regularly experiencing pain, muscle aches, brain fog, fatigue, depressed mood, and insomnia.
Patient’s pain eased considerably following celiac plexus block
The team noted that, given the abnormal buildup of ALA, PBG, and other porphyrins is what usually drives AIP symptoms, it’s not totally clear what was causing these symptoms.
The patient was eventually given bilateral splanchnic celiac plexus blocks by a pain specialist. This is a procedure that aims to block the activity of some of the nerves responsible for sensing pain and other sensations in the abdomen. The woman reported that her pain eased considerably following this procedure, though she continues to experience what she considers to be typical acute attacks every few months.
“This case highlights the importance of careful ongoing clinical observations of responses to medications and the possible benefits of implementing other treatments, like splanchnic nerve blocks as in our patient, to optimize patient care,” the researchers wrote.
Givlaari was developed by Alnylam Pharmaceuticals, which was not involved in this study.