E027

Adalimumab-Induced Hypophosphataemia: An Unknown Adverse Effect.

T Chopra, F Radia, J Cox, T Vakilgilani.

Imperial College Healthcare NHS Trust.

Abstract

Hypophosphataemia is a common electrolyte derangement in clinical practice, associated with a wide range of causes including drug-induced hypophosphataemia. Adalimumab, a tumour necrosis factor-alpha (TNF-α) inhibitor widely used in autoimmune diseases, has not been commonly linked to hypophosphataemia. Here, we describe a case of recurrent, treatment-resistant hypophosphataemia temporally associated with the initiation of adalimumab therapy, which subsequently resolved upon its discontinuation.

A 59-year-old woman of Bangladeshi origin was admitted in May 2025 with incidental severe hypophosphataemia (0.26 mmol/L) and hypomagnesaemia on routine outpatient bloods. She had multiple similar admissions since 2023 with varied symptoms including muscle spasms and myalgia. She denied any acute or chronic gastrointestinal losses, alcohol intake, or use of over-the-counter antacids.

Initial investigations on admission revealed low phosphate (0.26 mmol/L), low magnesium (0.46 mmol/L), normal calcium (2.41 mmol/L), normal parathyroid hormone (4.0 pmol/L), and low 25-hydroxy vitamin D (30 nmol/L).

Her past medical history included rheumatoid arthritis, type 2 diabetes, chronic kidney disease 3b (eGFR 30–40 mL/min), fatty liver disease with cirrhosis, hypertension and peptic ulcer disease. Additional history included a benign breast lesion (intraductal papilloma) and a necrotising granulomatous inflammatory pulmonary nodule resected via video-assisted thoracoscopic surgery (VATS). Her regular medications included Adalimumab, Hydroxychloroquine, Insulin, Metformin, Amlodipine and Omeprazole. She had previously been treated with methotrexate for rheumatoid arthritis, which was discontinued in 2023 due to abnormal liver function tests, after which she was switched to adalimumab.

On admission, she was treated with intravenous phosphate and magnesium, and a vitamin D loading regimen was initiated. Omeprazole was switched to Famotidine due to concerns that it might have been contributing to her electrolyte abnormalities. She was discharged on high-dose Vitamin D replacement.

Follow up at 1 month revealed ongoing hypophosphataemia. Her key biochemical findings and further investigation results were as follows:

	Normal range	Jul-24	Feb-25	Early May- 25	Late May-25
Phosphate (mmol/L)	0.8-1.5	0.23 ↓	0.26 ↓	<0.2 ↓	0.35 ↓
Calcium (mmol/L)	2.2-2.6	2.87 ↑	2.63	2.41	2.67 ↑
Magnesium (mmol/L)	0.7-1	0.57 ↓	0.41 ↓	0.46 ↓	0.50↓
PTH (pmol/L)	2.2-14	0.8 ↓	—	4	1.2
Vitamin D (nmol/L)	> 50	58.8	45.2 ↓	30 ↓	—
eGFR (ml/min)	> 90	—	38	30–33	32
FGF-23 (RU/ml)	<100			112 ↑
1,25 Vitamin D (pmol/L)	55-139			144  ↑
24-hour urine phosphate (mmol/day)	13- 42			<2.13↓
24-hour urine calcium (mmol/day)	2.5- 7.5			5.27 ↔
Urinary protein (g/L)	-			13 ↔

· PET CT 2024: pulmonary nodule and breast lesion (both were later identified as benign on biopsy)

· DEXA 2024: normal bone density

Though the FGF-23 level was mildly elevated, her 24-hour urinary phosphate excretion was low, with normal acid-base balance, normal urinary protein and only marginally raised 1,25 Vitamin D, making diagnoses of tumour-induced osteomalacia and renal tubular dysfunction less likely.

Notably, the onset of hypophosphataemia in 2023 coincided with the initiation of Adalimumab for the management of her rheumatoid arthritis.

Given the patient’s rheumatoid arthritis was stable, a decision was made with Rheumatology to temporarily withhold Adalimumab. This resulted in a normalisation of her biochemistry and symptoms, which have remained stable for four months following discontinuation of Adalimumab. These findings support the hypothesis of Adalimumab-induced hypophosphataemia. She is currently under close follow-up by the Rheumatology team, who are exploring alternative treatment options for her rheumatoid arthritis.

Although the underlying pathophysiological mechanism remains unclear, a potential association between tumour necrosis factor-alpha (TNF-α) inhibition and downstream effects on renal phosphate handling or systemic metabolism cannot be excluded. Furthermore, the presence of cirrhosis may have exacerbated hypophosphataemia in this patient, as chronic liver disease can impair gluconeogenesis and ATP turnover, thereby disrupting nutrient storage and promoting an intracellular phosphate shift ^[1,2].

This case describes a rare case of recurrent severe hypophosphataemia in a patient treated with Adalimumab. With the rising use of biologic therapies in multiple specialities, clinicians should remain alert to the potential of electrolyte disturbances as a possible adverse effect.

References

1. Nishikawa, T., Bellance, N., Damm, A. et al. (2014) ‘A switch in the source of ATP production and a loss in capacity to perform glycolysis are hallmarks of hepatocyte failure in advance liver disease’, Journal of Hepatology, 60(6), pp. 1203–1211. doi:10.1016/j.jhep.2014.02.014.

2. Dietrich, C.G., Götze, O. and Geier, A. (2016) ‘Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance’, World Journal of Gastroenterology, 22(1), pp. 72–88. doi:10.3748/wjg.v22.i1.72.