Hidradenitis Suppurativa: A Horrible Disease Afflicting Millions Worldwide
TrialSite News has been actively covering the serious skin disease and potential autoimmune-related disorder Hidradenitis Suppurativa (HS). Anywhere from 1 to 4 % of the developed world’s population struggles with what can be an extremely painful and debilitating disease. There is no cure, and many are treated with powerful immunosuppressive medications such as Humira. TrialSite News traffic is growing to the point of an emerging Patient Network. Many within this viewer network have identified that they struggle with HS. Recently, many in our HS network shared feedback and comments about our posting of recent positive Phase 2 bermekimab results. We believe that potentially 200,000 or more in the U.S. may struggle with HS. The consequences of HS are severe: it produces a chronic, painful and debilitating effect on many patients with moderate to severe cases. People with HS suffer from greater pain and associated psychological comorbidities, including depression, anxiety, disability, and impairments in quality of life compared to those with other dermatologic conditions. As if that wasn’t bad enough, there is a body of evidence linking HS to cancer.
Does HS Link to Cancer—Especially Skin Cancer?
Squamous cell carcinoma (known as SCC or cSCC) is the second most common form of skin cancer. Typically found on areas of the body damaged by UV rays from sun or tanning beds, it afflicts parts of the body we typically seek to protect including the head, neck, ears, lips, arms, legs and hands. It is a slow growing skin cancer. Unlike other forms of skin cancer, it can spread to the tissues, bones and nearby lymph nodes where it becomes harder to treat—and in some cases deadly.
Approximately 2.2 million people have cSCC at any given time making up about 20% of all skin cancer cases. According to one study 12% of males and 7% of females have developed cSCC at some point in time. Prognosis is generally good however, if it spreads it becomes a far more dangerous condition resulting in about 51,900 deaths globally per year. Unfortunately even with successful treatment it often reoccurs.
Research and Studies Connecting HS and Cancer
Some viewers in the TrialSite News Patient Network requested that we publish a research summary of any connection between HS and cancer. We exist for our viewers. What follows is a summary of the research effort.
In 1996 a group of medical researchers found that “the most feared, albeit rare, complication of HS in the perineal region is squamous-cell cancer.” These researchers referenced a paper back in 1982 in the Journal of Surgical Oncology titled Squamous Cell Carcinoma Complicating Hidradenitis Suppurativa by SB Black and JE Woods.
A paper was published way back in June 2001 titled Incidence of Cancer Among Patients with Hidradenitis Suppurativa. The authors’ investigated an HS population from 1965 through 1997—representing a total of 2119 Swedish HS patients. It was found that the risk of cancer developing in the HS cohort increased by 50%. The study authors concluded that HS patients faced a greater risk of nonmelanoma skin cancer. Moreover, buccal cancer and primary liver cancer also increased among the Swedish HS patient group. The Swedish researchers did caution that these findings should be interpreted cautiously due to a few factors including the combination of multiple significant testing and “the few observed cases” may have generated these findings.
In 2007 UK academic researchers Gael M Maclean and David J. Coleman published a report titled Three Fatal Cases of Squamous Cell Carcinoma Arising in Chronic Perineal Hidradenitis Suppurativa. The researchers presented three fatal cases of squamous cell carcinoma that results from HS in addition to a review of the past 40 years of published cases. Maclean and Coleman found that the male to female ratio of 4:1 and 61% of the cases were perineal or buttock. In their research they found no evidence of SCC arising from axillary (armpit) disease. On average the patient struggled with HS for 25 years prior to appearance of SCC but it could surface much sooner—as early as 3 years. 48% of the HS patients died within 2 years of the SCC diagnosis. Maclean and Coleman are clear as the risk when they advocate that HS appearance in “extra-axillary sites is a pre-malignant condition and should not be treated conservatively; curative resection is the mainstay of management.” Maclean
By 2010 a large group of academic researchers produced a report titled Clinicopathological Study of 13 Cases of Squamous Cell Carcinoma Complicating Suppurativa. This group concluded for SCC a prevalence of 4.6% in a sample of 217 cases and confirmed its predominance in men with potential involvement of human papillomavirus.
To come to their conclusion, they identified 52 cases of SCC complicating HS since 1958 and focused on 13 of the cases. The authors’ sought to include an investigation into human papillomavirus (HPV) in tumor samples by polymerase chain reaction (PCR) or paraffin-embedded material. The authors’ found that malignant transformation impacts men with a long-term history of genitoanal (genital) HS. They found that HPV was an influencing factor. They concluded that “SCC complicating HS evolves poorly, despite a good histological prognosis.” They end that their findings “sustain the implication of HPV in the malignant transformation of HS.”
In 2014 another interesting research result was published by Nordic academic researchers from Denmark and Sweden. Deirdre Nathalie Dufour (University of Copenhagen); Lennart Emtestam (Karolinska Institutet) and Gregor B Jemec (University of Copenhagen) produced a research article titled Hidradenitis Suppurativa: A Common and Burdensome, Yet Under-Recognized Inflammatory Skin Disease. Under a “Comorbidities” section of the report, the authors found that other studies point to increases in “epithelial and non-melanoma skin cancers.” According to these prominent Nordic academic medical center investigators, the risk of cancer with HS patients was 50% higher than “matched controls.” Moreover, the Danish and Swedish authors purport that there is “significantly increased risk for non-melanoma skin cancer, buccal cancer and liver cancer according to research completed by Lappins, Ye and Nyrén, et al reported on earlier in this article.
The Hidradenitis Suppurativa Foundation is a nonprofit public benefit corporation dedicated to improving the quality of life and care for individuals and families affected by HS. Since 2005, they have supported and encouraged worldwide research by developing and supporting an interdisciplinary family of scientists and physicians devoted to studying the molecular and cellular basis of HS with a goal of developing more effective and efficient treatments and preventative measures. According to their website squamous cell carcinoma (SCC) , the second most common skin cancer, “is considered the most severe complication of HS with prevalence of 0.5-4.6%” in the HS community. The foundation describes how the ongoing, chronic inflammation that result from draining HS lesions can possibly lead to skin changes at the cellular level which can lead to skin cancer. They note that dermatologists must be aware of this risk early in the diagnostic process.
TNF Blockers HS and Risks of Cancer (HUMIRA Leads the Pack)
According to studies the immunosuppressant adalimumab can provide some relief to HS patients. Humira dominates drug sale news and hence will be the focus of this section (with success comes responsibility and attention). First, AbbVie has incurred great research and development (R&D) expense to build a biological blockbuster drug. It has been approved for many indications by both the FDA and European Medicines Agency. There are other commercial sponsors that market TNF Blocker, monoclonal antibody-based treatments. We focus on AbbVie due to its’ tremendous success which should be celebrated. Although AbbVie has been accused of questionable distribution and marketing tactics associated with HUMIRA, so have the other big biopharmaceutical companies. They face tremendous shareholder pressure to maintain growth rates and hence stock price, and from time to time certain management in certain roles may succumb to intensified pressures and consider short cuts to continue sales velocity. We deplore this type of activity—it is not ethical and often not legal, but it happens in the fast-paced, market-driven American healthcare system; it is imperative that an educated and vigilant healthcare professional and consumer scrutinize the healthcare product choices (product and vendor) to appropriately select treatments and products that most meet the patient’s specific needs.
Humira (adalimumab), from some reports, works effectively on approximately 25% of HS patients according to two 36-week trials. HS patients face challenges however. The drug is pricey: it can cost up to $104,000 per year. Delivered via weekly injections, studies revealed that it does not cure patients and the effectiveness, at least in many cases, seemed to fade after initial 12 weeks of therapy. Nonetheless there is considerable future potential with adalimumab. AbbVie sponsored the PIONEER studies. The PIONEER clinical program consisted of two Phase 3 studies (PIONEER I & PIONEER II). They were designed to evaluate the efficacy and safety of Humira (adalimumab) compared to placebo in patients with moderate to severe HS. There were slight differences between PIONEER I and PIONEER II. The two trials included 633 patients with moderate to severe HS. The target primary endpoint was to determine the percentage of patients achieving HS Clinical Response (HiSCR) defined as an improvement in HS severity corresponding to at least a 50% reduction in total abscess and inflammatory nodule (AN) count relative to baseline, with no increases for abscesses and draining fistulas at 12 weeks. PIONEER I and II did produce results—patients that were treated with HUMIRA had reductions in the total number of abscesses and inflammatory nodules than patients on the placebo. During September 2015, the FDA approved HUMIRA for moderate to severe HS. The European Medicines Agency had already approved the drug for HS. As it received an “orphan drug designation” it afforded AbbVie the opportunity for a seven-year exclusivity for treatment of moderate to severe HS.
HUMIRA is the number one selling drug worldwide with approximately $18 billion in sales.
TrialSite News Patient Network HUMIRA Feedback
TrialSite News has rapidly generated a substantial viewer base since its’ inception in June 2018. Because we focus on independent, transparent and non-biased clinical research news we believe that a growing number of people struggling with various healthcare issues are visiting the website in greater numbers. We have developed a series of informal networks based on therapeutic and disease area including Hidradenitis Suppurativa (HS). We internally label this nascent social network as the TrialSite News Patient Network. Regarding HS alone we have hundreds of viewers engaged with our articles, news curation and research. We have elicited feedback from the HS network on Humira experiences. We include a few of these experiences for the readers benefit. In one case, a viewer with HS reports that they suspect, because of their Humira treatment, they were afflicted with psoriasis. Another viewer reported to us that after starting a Humira treatment doctors found a lump in their liver. Apparently, the lump didn’t form until the Humira treatment started; and it had stopped growing once the patient stopped the treatment. Another TrialSite News Patient Network viewer reported to us that that they believe their Humira treatment led to their lymphoma. Other reports include psoriasis and Crohn’s disease as well as irritable bowel syndrome (IBD), rapid weight gain and of course reports of cancer.
TrialSite News is a digital media outlet. We cannot medically substantiate these reports originating from the viewer network. They are anecdotal and not scientifically or medically validated—however we place a tremendous value on our patient network—and we share a tremendous amount of empathy for those viewers afflicted with HS. Especially in the case of moderate to severe HS, the pain and suffering can lead to debilitating consequences.
Our company is committed to these individuals seeking the truth about their conditions; transparency as to the relevant clinical research that they can benefit from in the future (or today); awareness as to who are the investigators and research sites conducting any relevant investigational research; and what is the agenda of the underlying commercial sponsor. Our hope is that this website can contribute to our viewers’ knowledge and understanding of present and future investigational treatments so that they can make better, more informed decisions. Back to HS and Humira.
HS and Humira Potential Side Effects/Risks
Many physicians are now prescribing Humira for HS since the FDA and EMA approvals back in 2015. AbbVie reports on a recent investor presentation (slide #15) that the approved label for HS is 160 mg/80mg /40 mg every week. They report it is under patent (part of their “patent estate) protection until 2031. The drug could produce up to $30 billion.
We don’t discount the 25% or so of those moderate to severe HS patients that are experiencing relief from HS thanks to Humira. Based on our viewers descriptions it can be life debilitating so for those that are benefiting from Humira we can only celebrate the results. However, use of Humira should not be treated lightly. A powerful TNF blocker, and monoclonal antibody, there are widely published side effects including cancer. According it its’ maker AbbVie the following are a risk:
“Serious infections have happened in people taking HUMIRA. These serious infections include TB, and infections causes by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections…”
“Cancer. For children and adults taking TNF blockers, including HUMIRA, the chance of getting lymphoma or other cancers may increase. There have been cases of unusual cancers in children, teenagers, and young adults using TNF blockers. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers including HUMIRA, your chance of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life-threatening if treated; tell your doctor if you have a bump or open sore that doesn’t heal.”
Prevalence of Hidradenitis Suppurativa
Prevalence of HS varies in the U.S., but a conservative estimate is at .10% in targeted populations. Few large standardized population-based studies with validated search strategies have been performed. Combine that with HS being misdiagnosed or not reported for fear of embarrassment we don’t know exactly how many people in the U.S. are afflicted with HS. Factoring in the prime working age population ages:25 to 64–there are approximately 172 million total population in the U.S. Incorporating the conservative HS estimate, we suggest the total HS population would be somewhere in the range of a few hundred thousand up to potentially a couple million people. Assuming 10% of this population may have severe cases (up to 200,000) and perhaps 10% of this subsegment are candidates for Humira treatments (20,000) the total available market equals $2 billion per annum. As we have reported, competition may be imminent with disruptive biotech ventures’ trials such as Bermekimab (XBiotech).
If Humira works well on the HS patient—with few major side effects–than it is well worth the price if payers (insurance) cover the bill. According to AbbVie, over 97% of national commercial and Medicare Part D patients have access to Humira as a preferred first-line targeted immunomodulator (TIM) on formulary.
Moderate to severe HS patients suffer greatly and the community is grateful for material relief. However, cancer is a documented risk. Humira has been so successful because of its positive impact in a few disease areas including HS-moreover according to a body of research, it has a known benefit-risk profile. As our viewers have requested a better understanding of HUMIRA cost justification, TrialSite News will undertake a survey of pharmacoeconomic analyses for a PriceWatch article coming soon.
Hidradenitis Suppurativa when moderate to severe represents a painful, debilitating skin disease associated with autoimmune disorders. There is a body of evidence that HS is associated with cancer in some cases—especially skin cancer known as Squamous cell carcinoma. (SCC) An emerging TrialSite News Patient Network has reported, at least anecdotally, of the potential for HS to lead to cancer, including SCC. It is important to note that SCC can turn deadly if it is not diagnosed properly and allowed to spread. Powerful new commercialized TNF blockers in at least a quarter of cases show they can make the patients’ lives better. However, they come with a price tag—side effects can include cancer. New investigational HS treatments are in the pipeline and may help provide greater relief from not only direct symptoms but also pervasive pain with improved safety profiles. Only time will tell. In the meantime, TrialSite News will continue to monitor the clinical reports daily.
Mr. O’Connor has spent nearly 20 years providing technology and value-added services to the clinical trials and health technology industry. An entrepreneur, he has been instrumental in building different ventures focusing on FDA 21 Part 11 enterprise document management, technology-enabled patient recruitment services, clinical safety data exchange, as well as population health and community care coordination for at-risk populations with Eccovia Solutions. He is a co-founder of a public benefit corporation launching a global clinical research site accreditation standard–ACRES ReServ. At TrialSite News, www.trialsitenews.com Mr. O’Connor and team have developed a comprehensive clinical research site data base and intelligent clinical news curation engine to contribute to clinical research transparency with a focus on sites and investigators. He earned his combined MA and JD from the University of California (Los Angeles and Hastings College of the Law) and undergraduate from San Francisco State University.