Background
Axial spondylarthritis (SpA) is a chronic inflammatory disease that predominantly effect spine. The terms Axial SpA encompasses both a non-radiographic form and a radiographic form which is also termed ankylosing spondylitis (AS). Patients generally presented with chronic back pain and morning stiffness. Peripheral arthritis, enthesitis, and dactylitis could also occur in the course of the disease. AS is more prevalent among men and it typically begins the third decade of life [1].
The main aims of treatment are relieving symptoms, and maintaining spinal flexibility and joint mobility. Non-steroidal anti-inflammatory drugs (NSAID) are the first-line drugs of AS treatment. Tumor necrosis factor (TNF)-alpha inhibitors (Anti-TNF) including etanercept are other options for patients with high disease activity index, despite conventional treatment. Secukinumab (anti-interleukin-17A monoclonal antibody) is also an efficient and safe treatment option [2].
Sexual health is important for quality of life. Thereby, rheumatologists should be aware of possible sexual dysfunction due to rheumatological disease. Previously, it has been shown that sexual functioning might be impaired in patients with AS [3]. The most frequent side effects of etanercept are injection side reactions, rash, abnormal hepatic function, and infection [4]. However, there might be some post-marketing side effects that clinicians could experience difficulties in recognizing and managing.
Here, we reported a patient with AS who suffered from ED under etanercept treatment.
Case Report
A 30-year-old male patient with an unremarkable medical history presented with increasing back pain persistent for 5 months. He was complaining of insidious onset pain with morning stiffness lasting about 10 minutes. The pain was worse at night and early in the morning and it improved with exercise. He did not have peripheral arthralgia, psoriasis, diarrhea, or uveitis. He had right-sided-enthesitis. There was no preceding history of trauma to the back or infection. He did not have a family history of rheumatological disease. He was sexually active and he had a regular partner. Laboratory values were as follows: white blood count 9,600/µl, serum c-reactive protein 9,1 mg/dl (reference range was < 5 mg/dl), and erythrocyte sedimentation rate of 4 mm in the first hour. Rheumatoid factor, anti-cyclic citrullinated peptide antibody, and antinuclear antibodies were negative. The human leukocyte antigen (HLA) B51 was positive but HLA B27 was negative. Sacroiliac joint X-ray film demonstrated sclerosis in the right sacroiliac joint. Sacroiliac magnetic resonance imaging revealed grade 3 sacroiliitis. NSAID provided adequate pain relief. A diagnosis of AS was made. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 3. Exercise was recommended. Despite a continuous regimen of two different NSAIDs for 10 months, the patient still had back pain. Etanercept was administered in combination with NSAID. One month later, under etanercept treatment, he presented with erectile dysfunction (ED) despite decreased back pain. He referred to urology. Physical examination, urinalysis, spermiogram, and urinary ultrasound did not reveal any pathology. His testosterone level was 600 ng/dl (reference range 280–800). Luteinizing hormone (LH) and Follicle-stimulating hormone levels were 6.03 ng/dl and 2.23 ng/dl respectively. He did not receive any specific medication including sildenafil for ED. He did not have any psychological stressor that might possibly cause ED. Etanercept was switched to secukinumab. ED was resolved within 1 week upon switching to secukinumab. He is still on the secukinumab treatment and he has not experienced ED during the 8-months follow-up.
Discussion
We reported a young adult male patient with AS who suffered from ED. Sexual dysfunction related to AS might be overlooked. Higher levels of ED among AS than the normal population were reported in the literature. Higher disease activity, longer disease duration, limited joint mobility, depression, and anxiety might be associated with sexual dysfunction in patients with AS. [5,6]. Disease activity might contribute in some extent to the ED in our patient but he did not have any depressive symptoms or anxiety which might be an indicator of another underlying cause besides disease activity. There is a scarce number of studies regarding the potential effect of anti-TNF therapy on ED [7]. In animal models, Carneiro et al. [8] displayed that TNF-a infusion in mice resulted in an increased contractile response, decreased non-adrenergic non-cholinergic nerve-mediated relaxation related to decreased endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) expression which could trigger ED [8]. Demirtas Sahin et al. [9] conducted a study on rats and their findings demonstrated inhibition of TNF with etanercept increases the eNOS and nNOS expression of cavernosal tissue and elevated testosterone levels. Thus, they concluded that TNF-antagonism might be used in the treatment of ED [9]. However, rat and human discrepancy should be taken into consideration in real-life practice. In a study from Korea, erectile function was assessed by a self-reported questionnaire, before and after anti-TNF treatment in AS patients. Erectile function significantly improved after treatment with anti-TNF in addition to diminishing disease activity [10]. Inflammation is related to ED [11]. Therefore, sexual dysfunction in these patients might improve due to the reduced inflammation and disease activity after treatment. On the contrary, Abhishek et al. [12] reported. One of their rheumatoid arthritis patients who experienced ED on etanercept treatment [12]. His symptoms improved after cessation of the drug. Moreover, Hidalgo-Rios et al. [13] reported a patient with Crohn’s disease suffered from ED under both adalimumab and sertolizumab. ED resolved after switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug) [13]. ED was resolved after etanercept discontinuation in our patients as well. The mean half-life of etanercept is 102 ± 30 hours [14]. Therefore, we would expect the effect of etanercept to diminish after a week of cessation, as observed in our patient.
There is a dilemma on the potential sexual effects of anti-TNF. Although in animal models, TNF antagonism has promising results as a therapeutic agent for ED; in real life, ED has been reported as a rare side effect of the anti-TNF especially in the early days of the treatment. On the other hand, sexual function might improve after several months of anti-TNF treatment probably due to the reduced disease activity.
Conclusion
We present a case of ED associated with etanercept in a patient with AS, resolved by switching to secukinumab. Therefore, we would like to highlight that ED might be a rare side effect of etanercept. Switching to an alternative agent might improve quality of life of patients.
What is new?
The authors reported a young male patient with AS who presented with ED under etanercept treatment. Even a prominent portion of AS patients experience ED, there is not enough data for potential effects of TNF-a inhibitors on ED. Additionally, to the authors’ knowledge, this is the first case reporting etanercept induced ED in an AS patient.