Introduction

Hidradenitis suppurativa (HS) is a chronic, inflammatory dermatosis that usually affects areas of flexural skin with dense hair follicles, such as the axillae, groin and genital area1. Depending on the severity of the disease, recurrent abscesses, nodules, fistulae and scars may occur throughout the disease process2. These can cause pain, bad odors and physical limitations in the affected area and can seriously affect quality of life2. The clinical management of HS and patient compliance are often challenging, and the efficacy and tolerability of current treatment options may be limited. In recent years, biological agents have gained importance in the treatment of dermatologists3. In particular, adalimumab, a TNF-alpha inhibitor, has been evaluated as a promising option for the treatment of HS and has become our treatment of choice in challenging cases of HS. However, the patient’s condition and risks should be carefully evaluated before this treatment is used. Adalimumab has been reported to cause hepatitis and tuberculosis reactivation because of its immunosuppressive effects, similar to those of other biological treatments4,5.

In our study, we aimed to investigate the rate of adalimumab use in HS patients followed up in our clinic and, contrary to other studies, hepatitis b and tuberculosis reactivation due to adalimumab only in HS treatment.

Methods

In this study, data from 462 HS patients followed up at Dicle University Dermatology Clinic between 1 January 2017 and 30 June 2024 were retrospectively analyzed. Adalimumab use was detected in 56 (12.12%) patients. Patients over 18 years of age and 54 (11.69%) patients who used adalimumab for at least 6 months were selected for this study. All the participants were divided into 5 subgroups according to their HBV serological test results: natural immunity, chronic HBV infection, isolated anti-HBcIgG positivity, vaccinated and susceptible. Hepatitis B reactivation was detected only in those with positive anti-HBc IgG (chronic HBV infection, isolated anti-HBcIgG positivity, and natural immunity) tests who were at risk of reactivation. To investigate reactivation, HBV DNA test results before and after biological treatment and ALT-AST levels during the continuation of biological treatment were examined. Patients with a positive HBV DNA test before biological therapy and an increase of > 1 log10İU/ml in the HBV DNA titer during biological therapy and patients with a negative HBV DNA test before biological therapy and a positive HBV DNA test during the biological therapy use period were considered reactivation positive. Patients for whom no HBV DNA test was performed during the study period, those who had one positive HBV DNA test result before or after biological treatment and the other test result was not investigated, and those who had never been checked after starting biological treatment were not included in the reactivation investigation. For tuberculosis reactivation, those who had a latent tuberculosis test (quantitative test), did not report any symptoms and were chronic carriers were included. Among the patients with a positive latent TB test and suspicious clinical and radiological evaluation during biological treatment, those with a positive culture were considered reactivation positive. Data were evaluated with the SPSS-21.0 statistical program, and the value, mean, median value, standard deviation, incidence and frequency of each parameter in all patients were recorded.

Findings

The mean age of the 54 patients receiving adalimumab was 32.11 years; 16 (29.63%) were female, and 38 (70.37%) were male. According to the hepatitis serological results of these patients, 27 (50%) were vaccinated, 15 (27.78%) were not vaccinated, and 12 (22.22%) were naturally immune, as shown in Fig. 1. Among the 12 patients at risk of hepatitis B reactivation during adalimumab treatment, 8 received entecavir, and 4 received tenofovir prophylaxis. No hepatitis B reactivation was observed in any of the 12 patients during adalimumab treatment.

Fig. 1
figure 1

Groups of patients treated with adalimumab according to hepatitis serological test results.

Full size image

In 54 patients, latent tuberculosis tests revealed that 4 (7.41%) were diagnosed with previous tuberculosis and received isoniazid prophylaxis for 9 months during treatment. No tuberculosis reactivation was detected in any of these 4 patients, as shown in Fig. 2. Although 1 patient was a carrier of both hepatitis B and tuberculosis, no reactivation was observed.

Fig. 2
figure 2

Groups of patients treated with adalimumab according to the latent TB test results.

Full size image

Discussion

Adalimumab, an anti-TNF drug, has recently come to the forefront as an important and frequently used treatment option for HS1,6.

However, owing to its immunosuppressive effects, it has been reported in many studies that it can cause reactivation in patients who are hepatitis B and tuberculosis carriers4,5.

Most of the studies on hepatitis b reactivation during adalimumab treatment have been published on rheumatological diseases.

Toshiyuki Watanabe et al. conducted a study on rheumatological patients and reported that 19 out of 152 patients used adalimumab and were at risk of hepatitis B reactivation. Hepatitis B reactivation was not observed in any of these 19 patients treated with adalimumab. However, unlike our study, detailed information on the use of prophylaxis was not included in this study7.

When the study by S. Piaserico et al. on psoriasis patients was analyzed, 17 patients treated with adalimumab were followed up for the risk of hepatitis B reactivation. None of the 7 patients at risk of reactivation developed reactivation, although they did not receive prophylactic treatment. Unlike in this study, although 10 of the 17 patients were HBsAg positive, no reactivation was observed during prophylactic treatment with adalimumab. This once again emphasizes the importance of prophylactic treatment during adalimumab treatment8.

A case series by D.J. No et al. revealed that adalimumab was preferred for the treatment of psoriasis lesions in 3 hepatitis B patients. Lamivudine was used prophylactically before adalimumab and throughout the treatment. Hepatitis B was controlled in these 3 patients, and no reactivation was detected in any of them. This case series demonstrates once again that prophylactic treatment with adalimumab is a safe choice, with no fear of hepatitis B reactivation during adalimumab treatment9.

When the study by Young Ho Lee et al. on 468 rheumatological patients at risk of hepatitis B reactivation was performed, 95 patients used adalimumab. Hepatitis B reactivation was detected in only one of these 95 patients. While it has been observed that this patient did not receive prophylactic treatment, the importance of prophylactic treatment is emphasized once again10.

  • Another treatment option recommended in international guidelines for the treatment of hidradenitis is infliximab, which shows TNF-alpha inhibitor effect like adalimumab11. If we look at the study conducted by Shunsuke Mori et al. in which 17 publications including 712 patients were analysed, including infliximab and adalimumab, reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for infliximab, 8.6% for tocilizumab, and 3.3% for rituximab12. The fact that the majority of patients with reactivation did not receive prophylactic treatment once again emphasises the importance of prophylaxis.

  • The study by Pérez-Alvarez et al. on 257 cases showed that the hepatitis B reactivation rate was 5% and that infliximab caused a higher rate of hepatitis B reactivation than adalimumab. Other information obtained in this study is that the percentage of reactivation was higher in patients previously treated with immunosuppressive agents (96% vs. 70%, p = 0.033) and lower in those who received antiviral prophylaxis (23% vs. 62%, p = 0.003)13. This once again emphasises the importance of prophylactic treatment like the data obtained in our study.

  • In the study conducted by Young Ho Lee et al. on 122 hepatitis B reactivation risk cases, TNF-alpha inhibitor etanercept was used in 56 cases, adalimumab in 25 cases and infliximab in 14 cases14. Hepatitis B reactivation was observed in 6 patients using TNF-alpha inhibitors, 4 of whom used etanercept and 2 of whom used infliximab. Antiviral prophylactic treatment was given only in one patient using etanercept. However, the American Gastroenterological Association recommends antiviral prophylaxis for patients at risk of hepatitis B reactivation during immunosuppressive therapy and for up to 6 months after discontinuation15.

Considering all these studies, although adalimumab has a risk of hepatitis B reactivation, this risk is very low and can be completely prevented with prophylactic treatment. However, when the literature is reviewed, the overwhelming majority of the studies are on rheumatological diseases and psoriasis. Studies on the risk of hepatitis B reactivation with adalimumab use during the treatment of hidradenitis suppurativa are very rare. With our study, we wanted to fill this large gap in the literature and contribute to future studies. Our study revealed that adalimumab is a safe choice in terms of hepatitis B reactivation in the treatment of hidradenitis and can be completely prevented with prophylactic treatment.

It has been reported in the literature that reactivation may develop with the use of adalimumab in latent tuberculosis carriers5.

In the study by Abdullah Al-Sohaim et al., 410 patients receiving adalimumab treatment, including only 6 patients with hidradenitis suppurativa, were investigated for tuberculosis reactivation. A total of 26 of 410 patients, the majority of whom were rheumatological patients, were at risk for tuberculosis reactivation, and all 26 of these patients had rheumatological diseases. All 26 patients received isoniazid prophylaxis, and no reactivation was observed in any of them. In parallel with our study, this study once again emphasized the importance of prophylaxis in preventing tuberculosis reactivation, but unlike our study, it cannot clearly demonstrate the risk during the treatment of hidradenitis suppurativa16.

In contrast to our study, the case of Freddy Caldera et al. involved a patient with Crohn’s disease who was at risk of tuberculosis recurrence and developed tuberculosis reactivation despite receiving prophylactic treatment17. However, since our study focused on hidradenitis suppurativa, risk similarity in terms of tuberculosis reactivation cannot be predicted.

When Ariana Ellis et al. examined hidradenitis suppurativa patients, 170 HS patients receiving biological treatment were included in the study. In the present study, reactivation was observed in 4 of the 9 high-risk patients, and 1 of them used adalimumab18. However, it is impossible to comment on adalimumab since it is not specified in detail which biologics all 9 risky patients received. Although our study was similarly based on patients with Hidradenitis suppurativa, unlike this study, tuberculosis reactivation was investigated only in patients treated with adalimumab. This is another piece of data that makes our study valuable.

When the literature is reviewed, to our knowledge, our study is the first study on tuberculosis reactivation in hidradenitis suppurativa patients receiving adalimumab treatment.

Conclusion

The TNF-alpha inhibitor adalimumab has recently been shown to be a safe and effective choice for the treatment of suppurative hydradenitis. In addition, HBV and latent TB screening should be performed before starting adalimumab treatment, and antiviral prophylaxis should be applied if necessary.

Of course, not only hepatitis B and tuberculosis but also other infectious agents should be taken into consideration in pre-treatment planning. Before starting adalimumab, the vaccination history should be reviewed, missing vaccines should be completed and, if possible, live-attenuated vaccines such as herpes zoster should be administered at least 4 weeks before the start of treatment19,20. If the patient is in the process of treatment, live vaccines should be strictly avoided and non-living vaccines (Shingrix®) should be preferred among both live (Zostavax®) and non-living vaccine (Shingrix®) options such as herpes zoster21,22. The current EULAR (European League Against Rheumatism) guideline on vaccination programme can be taken into consideration23.

In addition, hepatitis screening every 6 months and latent TB screening every year should not be neglected. In this way, possible complications during the treatment process can be minimized, early diagnosis and treatment opportunities can be obtained, and patient safety can be ensured.