I. Introduction

Currently, there is growing research on the role of biologic therapies in HS. Biologics are injectable medications that target small molecules in the immune system that cause inflammation. These include tumor-necrosis factor (TNF), interleukin-1 (IL-1), IL-12, IL-23, and IL-17. Biologics bind to these molecules, and prevent them from causing inflammation in the body. This lowers inflammation from HS.

II. Tumor Necrosis Factor (TNF) Inhibitors

Tumor necrosis factor (TNF)-alpha inhibitors bind to TNF-alpha. TNF-alpha plays a role in causing inflammation. This medication blocks its function and decreases inflammation.

Adalimumab is a TNF-alpha inhibitor. It is known by the brand name Humira®. Adalimumab is the only drug federally approved by U.S. Food and Drug Administration (FDA) to treat moderate to severe HS. It can be used in adults and adolescents 12 years or older who weigh more than 30 kg (66 lbs). Adalimumab is self-injected using a syringe or pen injector. Typically, adalimumab dosing is 160 mg at week 0, 80 mg at week 2 and then 40 mg weekly or 80 mg every two weeks starting at week 4. Some people may benefit from a higher dose. Large clinical trials, with a total of more than 800 people with HS, have shown adalimumab to be safe and effective. A recent trial also demonstrated that adalimumab is safe to continue while undergoing surgical excisions for HS: after surgery, there was no increased risk of complications with continued therapy.

Infliximab is a TNF-alpha inhibitor known by the brand name Remicade®. You cannot receive infliximab at home. It is given as an IV (intravenous) infusion in a clinic or hospital. The prescribed dosage is based on weight. This allows physicians to change dosing to get better results. The standard dosage is 5-10 mg/kg at week 0, 2, and 6, then every 4-8 weeks after that. Infliximab is not FDA-approved for HS. However, several small clinical trials and studies suggest infliximab is effective in HS.

Sometimes, the body can make antibodies against biologics. These will bind to the medication, making it less effective. An immunosuppressant medication, such as methotrexate, may also be taken to try to prevent this antibody formation from happening.

Infliximab can cause infusion reactions, which may happen immediately. Symptoms may include itching, shortness of breath, flushing, and/or headache. Less commonly, more severe reactions can occur. These symptoms may include fever, skin rash, breathing issues, and blood pressure changes.

Mild IV infusion reactions can sometimes be treated by slowing how fast the medication is given through the IV. With severe reactions, the treatment may need to be stopped. Sometimes, medications can be given prior to the infusion to help lower the chance and severity of these reactions. Examples include antihistamines, fever-reducing medications, or steroids. However, more research is needed on how effective these agents are in preventing IV infusion reactions.

Other TNF-alpha inhibitors include etanercept (Enbrel®), golimumab (Simponi®), and certolizumab (Cimzia®). Etanercept is currently not recommended for HS. It did not improve HS symptoms in patients in small trials. Both golimumab and certolizumab were found to improve HS in small studies. Golimumab can be given as an infusion or injection. Certolizumab is given as an injection. Certolizumab does not cross the placenta so it may not affect a developing baby during pregnancy. If you are pregnant or planning for pregnancy, your healthcare provider may bring up this medication as a possible treatment option.

III. Other Biologics

Interleukin (IL)-1 Inhibitors. IL-1 inhibitors bind to and block the function of IL-1, a molecule that promotes inflammation. Canakinumab (Ilaris®) and anakinra (Kineret®) are both IL-1 inhibitors that are given as injections. Canakinumab is dosed at 150 mg every 4-8 weeks. Anakinra is dosed at 100 mg every day. Since anakinra requires daily injections, this may be a barrier for some people. Both medications have been found to be helpful in small, limited studies of people with HS, including some who also have pyoderma gangrenosum (PG). PG is a condition that causes large, painful ulcers on the skin, most often on the lower legs. More information about other diseases associated with HS can be found in Chapter 6. Your healthcare provider may be more likely to discuss one of these medications with you if you have both HS and PG.

IL-12/23 Inhibitors. Guselkumab (Tremfya®), risankizumab (Skyrizi®), and tildrakizumab (Ilumya®) bind to IL-23. Ustekinumab (Stelara®) binds IL-12 and IL-23. These medications block the pro-inflammatory actions of IL-12 and IL-23. They are given as injections every eight (guselkumab) or twelve (risankizumab, tildrakizumab, ustekinumab) weeks for people with psoriasis. Doses for patients with HS may need to be more frequent. Small studies on the use of guselkumab for patients with HS had been promising. However, a recent clinical trial on guselkumab did not meet its treatment efficacy goals. More research is needed on the efficacy of IL-12 and IL-23 biologics for patients with HS.

IL-17 Inhibitors. Secukinumab (Cosentyx®), ixekizumab (Taltz®), brodalumab (Siliq®), and bimekizumab (Bimzelx®) bind to IL-17 and block its function in the immune system. These IL-17 inhibitors are typically given as injections every two (brodalumab) or four (secukinumab and ixekizumab) weeks for people with psoriasis, and for people with HS the dosing may need to be more frequent. Studies on the use of IL-17 inhibitors for patients with HS have been promising. In fall 2022, it was shared that two large HS trials for secukinumab showed greater response rates for secukinumab compared to placebo. In winter 2022, we learned that two large HS trials for bimekizumab showed superior response rates for bimekizumab compared to the placebo. Each of these trials had over 500 people with HS enrolled.

Small Molecule Inhibitors. Tofacitinib (Xeljanz®) is an immunosuppressant that binds and inhibits Janus kinase (JAK) proteins. Blocking JAK interferes with one of the immune signaling pathways in the body. There are different JAK proteins. Tofacitinib inhibits JAK1, 2, and 3. It has been reported as helpful for a few people with HS who had previously not responded to multiple biologics. Povorcitinib, a JAK1-selective inhibitor, hadpromising results in an early phase trial that enrolled over 200 people with HS. Two larger trials are planned to further explore how effective and safe povorcitinib is as a treatment for HS.

Sirolimus is a different medication that blocks mTOR, which is also involved in signaling pathways in the body. Like tofacitinib, sirolimus suppresses the immune system. At this time, sirolimus has only been studied in a few people with HS who were on biologics that were not fully effective at controlling their HS disease. Sirolimus was prescribed to these individuals as an additional treatment, with reported benefits.

More studies are needed to see if these small molecule inhibitor medications are good treatment options for HS and to determine how best to use them

IV. Comorbidity Considerations

Biologics are a treatment option for many different conditions. These include psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Therefore, one biologic treatment may adequately treat multiple conditions in people with HS. Your healthcare provider can help choose the best treatment for you based on your medical history. It is helpful to share your preferences regarding type of treatment, dosing regimen, and lab monitoring schedule with your healthcare provider so you can make treatments decisions together.

V. Side Effects of Biologics

Injection Pain and Reactions. Injections can be uncomfortable. Insertion of the needle may cause pain. There can also be pain while the medication is being injected. Steps can be taken to reduce injection-related pain (see Q&A section).

Sometimes, a skin reaction may occur at the injection site. This can look like red patches that appear minutes to hours after the treatment. Medications like topical steroid creams, antihistamines, non-steroidal anti-inflammatory drugs (such as Ibuprofen®), or acetaminophen can treat this. Cold packs may help as well. In rare cases, severe pain or swelling may occur at the injection site. If you have an injection site reaction, you should let your healthcare provider know.

Infection Risk. Because biologics modulate the immune system, you may have a higher risk of getting infections while you are on a biologic. Sometimes, a biologic therapy can reactivate that are present but not active in your body. These infections include Hepatitis B and tuberculosis. It is important to screen for both of these before starting a biologic therapy. While taking certain biologics, it is also recommended to screen for tuberculosis every year. Different biologics have different needs for lab monitoring. If you are starting a biologic, you should discuss with your healthcare provider what your lab monitoring schedule will look like.