麻豆传媒

To clear the air from the outset, treating hidradenitis suppurativa (HS) has always been challenging.

Many patients delay seeking treatment until the condition has reached moderate or severe stages. Others seek help earlier, only to face misdiagnosis and misunderstanding by clinicians who are not familiar with the condition or who do not take the time to understand HS or its impact on patients.

A third obstacle relates to the therapies used to treat HS. Until 6 years ago, clinicians and their patients had no FDA-approved drugs for HS. Since the approval of adalimumab (Humira) in 2015, no other therapies for HS have been approved in the U.S. Clinical trials are underway with several promising biologic agents, but another approval is likely 2 to 4 years away.

Finally, an incomplete understanding of the pathophysiology of HS contributes to treatment challenges.

"Part of the pathophysiology, we know about, but part of the puzzle is unknown," said Afsaneh Alavi, MD, of the Mayo Clinic in Rochester, Minnesota, speaking earlier this year during the American Academy of Dermatology (AAD) virtual meeting. "We know there are multiple factors involved in the pathogenesis of the disease, including genetic, environmental, and bacterial factors. That's why our treatment also is multimodal ... Treatment includes systemic therapy, topical therapy, treatment of flares, and surgical therapy. When it comes to medical therapy, sometimes you use multiple oral treatments."

Clinical Guidance

Consistent with a multifactorial etiology and pathogenesis, the for managing HS emphasize multimodal treatment strategies. Topical agents, intralesional therapy, and systemic treatment all have a role in managing HS, often in concert with surgery. Though surgery is often associated with more advanced stages of HS (Hurley II and III), selected patients with stage I disease might benefit from limited surgical intervention.

"In early one-stage disease, medical management with a topical or possibly a combination of topical and systemic therapy often is sufficient to keep the patient's skin under control," Alok Vij, MD, of the Cleveland Clinic, told 麻豆传媒. "For some patients, even with mild disease, if it's in a limited area, a surgical intervention might be enough to give the patient a quote-unquote 'cure' in that region for a durable amount of time."

However, HS often has an unpredictable clinical course, he added.

"We don't know how to predict which patients might develop hidradenitis in one underarm, for instance, and then years later develop lesions in another area," said Vij. "We don't know who will develop Hurley stage I in one location and then 2 days later in another location. We just don't have the data to predict."

"Surgery can be a great option for patients with Hurley I, if it is limited, but they might develop disease somewhere else down the line, because we're really not altering the overall biology; we're just altering the local environment," he noted.

In her AAD presentation, Alavi summarized the types of therapy used to treat HS and recent published results:

• Antimicrobial wash with chlorhexidine or benzoyl peroxide -- as compared with prescription therapies

• Topical resorcinol -- in 52 of 61 patients at 12 weeks; better response in Hurley I than II; decrease in abscesses and nodules; significant improvement in pain and quality of life

• Intralesional steroids -- in inflammatory nodules or pain as compared with saline control; with ultrasound-assisted intralesional treatment for flares and prior to surgery

• Tetracycline family of antibiotics -- in HS score and multiple patient-reported outcomes; response associated with lower body mass index, Hurley stage III, higher number of boils at baseline

• Clindamycin plus rifampicin -- Guideline-recommended for moderate or severe HS; clindamycin has good coverage of staphylococcal and streptococcal infections, carries a risk of Clostridium difficile and bacterial resistance; rifampicin has good coverage of S. aureus and coagulase-negative staphylococcus but confers a risk of drug-drug interactions and development of resistance

• Metronidazole -- Option for heavy stage I or II; contraindicated for patients who use alcohol; limited to short-term use because of neuropathy risk

• Ertapenem -- Best option as a bridge to surgery; broad-spectrum coverage; dramatic effects within 6 weeks

• Dapsone -- Antimicrobial, anti-inflammatory, and antineutrophilic properties

• Spironolactone -- in pain, lesion count, and physician global assessment score after 6 weeks of treatment

• Isotretinoin -- for patients with HS and dissecting cellulitis of the scalp, but recurrence was fairly common; for patients with pilonidal cysts; in combination with adalimumab

Alavi also touched on the use of complementary and alternative medicine, which is widespread among patients with HS. Patients who use alternative and complementary medicine spend an average of $500 a month on the treatments, she said. Many patients turn to alternative therapies because of their . Whatever the reason, clinicians should be aware that many patients use complementary and alternative therapies.

The therapies in the North American clinical guidelines for HS include only one drug that comes with a grade A recommendation (supported by consistent, good-quality evidence). Recommendations for many of the therapies are grade C (consensus opinion, case studies), and the rest are grade B (inconsistent or limited-quality evidence).

Adalimumab and Beyond

Adalimumab won FDA approval on the basis of two randomized, evaluating two different doses of the tumor necrosis factor (TNF)-alpha inhibitor. Adalimumab led to clinical response rates of 41.8% and 58.9%, whereas about a fourth of patients responded to placebo. The drug is indicated for patients age 12 or older with moderate or severe HS.

For most patients with Hurley I, the treatment paradigm begins with topical agents.

"Topical agents help keep the hair follicles open to reduce the bacterial load on the surface of the skin," said Vij. "Products like topical antibiotics or benzoyl peroxide-based washes are often the starting point. Once a patient goes a little bit beyond the early stages, treatment still begins with a week- or up to a month-long course of antibiotics, usually one of the anti-inflammatory antibiotics in the tetracycline class. If that doesn't work, then we usually move on to a combination of antibiotics."

"The data are still relatively new for adalimumab and especially some of the other biologics, so some dermatologists are a little bit less aggressive about starting a biologic for hidradenitis. I probably have a lower threshold in many cases," he said.

Many insurers have a step-care process for HS, Vij continued. Treatment has to begin topical therapy and then move on to oral antibiotics before trying a biologic agent.

"I'm hopeful that the landscape shifts in the near future and we recognize that patients who have widespread or severe disease can start a biologic agent sooner rather than later," said Vij.

For Joslyn Kirby, MD, of Penn State University in Hershey, a 3- to 4-month trial of therapy provides the clinician and the patient a good idea as to whether the treatment is helpful.

"I try to give any therapy -- whether it's a topical or an oral antibiotic or spironolactone or metformin, even biologics -- 3 or 4 months to show what it's capable of doing," she said.

In the two pivotal trials of adalimumab, about half the patients randomized to the TNF inhibitor did not respond. For those patients, the treatment paradigm continues to evolve. Kirby said she has had some success switching patients from adalimumab to another TNF inhibitor -- infliximab (Remicade), which is not approved for HS. Other biologics, notably anakinra (Kineret) and ustekinumab (Stelara), have shown promise in limited clinical evaluations involving patients with HS.

"If adalimumab doesn't work for a patient, we have had the least hassle [from insurers] with moving on to a drug like infliximab," said Kirby. "When you start looking at interleukin-17 inhibitors, interleukin-1 inhibitors, phosphodiesterase inhibitors -- some of these drugs are just not accessible to patients unless the company has a really good support program or the patient has excellent insurance."

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