Three Drug Approvals and a Safety Warning

FDA Approves Avsola – Biosimilar for Remicade

The FDA approved Avsola (infliximab-axxq) injections, a biosimilar to Remicade (infliximab). This drug is indicated for the treatment of:

  • Crohn’s Disease
  • Ulcerative colitis
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Psoriatic arthritis
  • Plaque psoriasis

Dosing guidelines vary significantly per indication. Adverse reactions include infections, infusion-related reactions, headache, and abdominal pain.

In various industries, workers may develop various forms of arthritis due to cumulative or acute trauma, resulting in the prescription of osteoarthritis drugs. This has led to certain specialty medications for inflammatory conditions appearing in workers' comp claims, with drugs for other arthritis conditions being prescribed off-label. Furthermore, it is possible for occupational injury to aggravate pre-existing inflammatory joint disease that may have been previously mild.

FDA Approves Dayvigo for Insomnia

The FDA has approved Dayvigo (lemborexant) tablets for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

In workers’ comp populations, insomnia is a common side effect from opioid therapy. In the event patients are prescribed medication to treat insomnia, Dayvigo could make its way into workers’ comp claims.

Please work with your pharmacy team to ensure appropriate insomnia treatment options are selected.

Dayvigo should not be used by patients with narcolepsy. Adverse reactions include drowsiness. For further information, read the FDA-approved drug label.

FDA Approves Ubrelvy for Migraine

The FDA approved Ubrelvy (ubrogepant) tablets for the treatment of migraine with or without aura. Ubrelvy is not indicated for the preventive treatment of migraine, and will be available in 50 mg or 100 mg doses.

In workers’ comp, migraines can arise as a result of traumatic head injury, or certain injuries can exacerbate preexisting migraine disorders.

Adverse reactions of Ubrelvy include nausea and somnolence.

FDA Warns About Breathing Problems for Pregabalin and Gabapentin

The FDA issued a warning that serious breathing difficulties may occur for individuals taking gabapentin or pregabalin who have respiratory risk factors. These risk factors can include the use of opioid pain medications and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease (COPD) that reduce lung function.

Gabapentin (Neurontin®, Gralise®, and Horizant®) and pregabalin (Lyrica®, and Lyrica® CR) are used for a variety of conditions, including seizures and nerve pain, conditions which are common in workers’ compensation. It is therefore possible that injured workers could be taking gabapentinoids along with opioids, leading to potential breathing difficulties.

Furthermore, as prescribers shift away from opioid pain medications, the prescribing of gabapentin and pregabalin has increased, meaning that a larger pool of patients and injured workers could be at risk of these breathing difficulties if they are predisposed to respiratory risk.

Tags: Avsola, Remicade, infliximab, biosimilar, arthritis, rheumatoid arthritis, Dayvigo, insomnia, lemobrexant, Ubrelvy, migraine, ubrogepant, gabapentin, pregabalin, breathing, respiratory

Psilocybin for Mental Health Disorders?

In late November of 2019, psilocybin, the active ingredient in hallucinogenic "magic mushrooms," was designated as a breakthrough therapy for major depressive disorder (MDD) by the FDA.

This decision was based on the Usona Institute's recent initiation of a Phase 2 clinical trial to evaluate potential efficacy of a single 25mg oral dose of psilocybin in 80 patients with MDD. The primary endpoints of this trial will compare changes in depression scale from baseline when compared to placebo.

While primary completion of the trials are estimated for February 2021, the FDA previously granted Breakthrough Therapy status to psilocybin in 2018 for treatment-resistant depression. This designation was granted after the start of a different Phase 2b trial involving 216 patients across Europe and North America.

In fact, a quick search for psilocybin at ClinicalTrials.Gov reveals 27 studies that are either recruiting, active and not recruiting, or enrolling by invitation. Currently a Schedule I drug, there have been various efforts to study the potential therapeutic uses of psilocybin for many years.

John Hopkins University launched the Center for Psychedelic and Consciousness Research in September of 2019, dedicated to furthering the study of psychedelic drugs’ potential applications to legitimate medical care. Among their goals is to study psilocybin’s chemical effectiveness as a new therapy for mental health disorders, opioid addiction, and more.

Most recently, John Hopkins researchers published a recommendation in Neuropharmacology that psilocybin be rescheduled from a Schedule I drug to a Schedule IV drug, once the drug clears Phase 3 clinical trials. These researchers compared psilocybin to typical drugs of abuse, based on eight factors of the U.S. Controlled Substance Act, and determined the abuse potential of medical psilocybin to be low and manageable when administered according to a medical model that addresses these concerns.

A separate literature review conducted by the Journal of Psychiatric Practice investigated the published literature regarding the psychotherapeutic uses of hallucinogens in psychiatric disorders. The majority of studies reviewed demonstrated significant associations with improvement in the condition investigated. However, it was difficult to draw definitive conclusions as most studies suffered from small sample sizes, inconsistent measures, and poor study design, indicating the need for more research.

As psilocybin has shown effectiveness in treating certain mental disorders, and as research advances, psilocybin could make its way into patient care, and perhaps one day into workers’ comp.

Tags: psilocybin, depression, FDA, mental health, mental illness, mushroom, John Hopkins

MDMA Gains Steam for PTSD Treatment

It is well known that post-traumatic stress disorder (PTSD) is compensable in many states as a primary condition under workers’ compensation for certain high-stress occupations such as first responders, and as a secondary mental condition when PTSD results from a traumatic physical injury.

While the FDA recently Fast Tracked a new PTSD drug in development, there have been few advances in the treatment options for PTSD. However, a new body of research is looming on the horizon, and that is the potential use of methylenedioxymethamphetamine (MDMA), also known as the party drug “ecstasy” or “molly,” in special psychotherapy sessions for the treatment of PTSD.

The FDA has granted Expanded access to MDMA-assisted psychotherapy for PTSD, allowing select patients early access to this therapy, recognizing it a potentially beneficial investigational therapy for people facing a serious or life-threatening condition for who current options have not worked, and who are unable to participate in Phase 3 clinical trials.

Back in 2017, the FDA granted Breakthrough Therapy designation to MDMA-assisted psychotherapy for PTSD, agreeing on special protocol assessments for Phase 3 clinical trials. This designation demonstrates the FDA’s belief that this treatment could provide significant improvement over existing therapies.

The FDA’s confidence on this therapy was based on Phase 2 clinical trials where 56% of patients that underwent MDMA-assisted psychotherapy no longer qualified for PTSD after a two-month follow-up; approximately 12 months after MDMA-assisted psychotherapy, that number went up to 68%.

So how does MDMA-assisted psychotherapy work? According to an extensive article from The New York Times, MDMA-assisted psychotherapy involves three regular psychotherapy sessions. On the fourth session, the patient takes a pill of MDMA and lies in a relaxing area with two therapists (one male, one female) for an eight-hour session.

During this intensive session, the patient processes complex emotions and insights. The dosage of MDMA is believed to flood the brain with hormones and neurotransmitters that evoke feelings of trust and well-being, which researchers say allows patients to re-examine traumatic memories. During follow-up psychotherapy sessions, patients process the insights gained during their MDMA sessions; current protocol calls for patients to undergo MDMA-assisted therapy sessions two-to-three times, with each session a month apart and interspersed with more standard psychotherapy.

Researchers did not find MDMA or therapy alone to be as effective, believing the MDMA to be a catalyst that allows healing to happen.

Various members of the scientific community have found these findings to be valid. The Lancet Psychiatry found Phase 2 trials to show much promise, as did the journal Psychopharmacology, which supported expansion into Phase 3 trials.

Currently, the Multidisciplinary Association for Psychedelic Studies (MAPS), the organization conducting the Phase 3 trials, has two trials underway, both of which will be randomized double-blind, placebo-controlled, multi-site trials that assess the safety and efficacy of MDMA-assisted psychotherapy in 200-300 patients with severe PTSD.

The first trial, which as of September of 2019, has enrolled subjects in all 15 research sites, will randomize three sessions of either MDMA or placebo in conjunction with psychotherapy over a 12-week treatment period, along with non-drug preparatory and integration sessions. The primary outcome measure of the study is the Clinician-Administered PTSD Scale (CAPS-5), a semi-structured interview used in the majority of clinical trials for PTSD. Additional measures will be used as well.

The second trial is still in the recruitment stage, but according to ClinicalTrials.Gov, there are approximately 20 studies involving MDMA in various stages.

Tags: MDMA, ecstasy, molly, PTSD, psychotherapy

Lavender Administration Shows Promise for Anxiety

Healthcare consumers have demonstrated an increased interest in alternative therapies over the last several years, and this trend has increased even further as populations continue to diversify.

An estimated 32-40% of millennials are open to alternative therapies including acupuncture, herbal remedies, and massage therapies, and are less likely to use traditional prescription drugs than previous generations. In fact, 25% of millennials use alternative therapies more than conventional options.

Organizations such as Harvard, Stanford, Duke University and the Mayo Clinic have established alternative or complementary medicine programs, and clinical evidence is surfacing in favor of some alternative care remedies.

A recent systematic review and meta-analysis conducted to assess the efficacy of lavender, in any form and way of administration, on anxiety and anxiety-related conditions, was recently published in Phytomedicine.

Lavender administration has frequently been suggested as a possible treatment for anxiety, both in alternative medicine and in clinical research, and this study identified 65 randomized controlled trials (RCTs) and 37 non-randomized studies (NRSs), which included patient data from 1,200 participants.

Approximately 54 RCTs and 25 NRSs reported at least a significant result favoring the use of lavender for anxiety.

The analysis found that lavender inhalation can significantly reduce anxiety levels measured with any validated scale, as well as state anxiety and trait anxiety. Measures utilized included the Zung Self-rating Anxiety Scale, the Hamilton Anxiety Scale, and the State-Trait Anxiety Inventory (STAI). However, lavender inhalation did not show a significant effect in reducing systolic blood pressure as a physiological parameter of anxiety.

Utilizing the Zung and Hamilton anxiety scales, a significant effect in diminishing anxiety levels was found in favor of Silexan® (lavender oil) for a least six weeks, with similar measures found in the administration of massage with lavender oil.

Researchers concluded that lavender treatment could be a therapeutic option for the treatment of anxiety, as lavender is simple, safe, and generally inexpensive. However, a majority of the trials were characterized by a high overall risk of bias, and there was a heterogeneity of study designs, indicating a need for more research.

Tags: Lavender, anxiety, alternative therapy, millennials

Keeping an Eye Out for CBD

Medical marijuana has seen much attention over the last few years, but very few have discussed the rise of cannabidiol (CBD) products that are derived from marijuana.

While there are certain FDA-approved drugs containing CBD, such as Epidiolex, there has been an explosion of CBD-containing products that have not undergone any clinical trials, yet they are still marketed for various indications. Particularly relevant to workers’ comp, some of these indications include:

  • Pain
  • Muscle spasms
  • Anxiety and depression
  • Sleeplessness
  • Opioid dependency
  • PTSD
  • Brain injury

CBD products are, in theory, supposed to lack tetrahydrocannabinol (THC), the compound responsible for the euphoric effects of marijuana, and offer various clinical benefits. However, depending on sourcing and quality, this may not in actuality be the case, and some CBD products could inadvertently contain THC.

But even if CBD products contained no THC, the belief that CBD products are not euphoric has led members of the public to assume that these products are safer, despite a lack of clinical evidence. While initial research does indicate that CBD can offer certain clinical benefits for particular medical conditions, more research is necessary to clarify those benefits against potential risks.

Unfortunately, the public’s misconceptions have been inappropriately marketed by certain manufacturers of CBD products. The FDA is aware that some companies appear to be marketing products containing cannabis and cannabis-derived compounds in ways that violate the law.

The FDA displayed concern that the marketing of these products could put the health and safety of consumers at risk, by claiming to prevent, diagnose, mitigate, treat, or cure serious diseases, influencing patients not to use approved therapies. And though the FDA has issued warning letters to companies selling unapproved CBD products, the agency does not have a policy of enforcement discretion with respect to any CBD products.

This is especially alarming considering the explosion of CBD products available on the market; CBD products are not just found in smoke shops, but in health food stores, corner markets, gas stations, and even in CVS and Walgreens, and they are available in a myriad of formulations such as oils, capsules and pills, and other edibles such as gummies and candies, or topicals, sublingual picks, vape pens, bath bombs, pet treats, coffee, ice cream, energy drinks, beers and protein bars, vaginal suppositories, and much more.

But how does this impact workers’ comp?

Unbeknownst to the claims and medical professionals teams, not only could patients be using CBD products to treat pain, muscle spasms, and other common ailments associated with an injury, but patients who are adhering to their workers’ comp therapy could be using CBD products for unrelated concerns.

CBD lotions to cleanse the skin are popular, as are smoothies that claim to offer digestive benefits; the number of trendy applications for CBD is skyrocketing, and with such limited clinical understanding regarding the impact of these products, patients could be exposing themselves to a variety of risks.

It is unknown how CBD may interact with common workers’ comp medications, and it is not known how much CBD is safe to consume daily, especially if patients are using multiple CBD products. For instance, a patient may apply a topical CBD lotion, then consume a CBD smoothie or candy, then use CBD oils and soaps, making it difficult to ascertain the total consumption associated with various CBD products.

Claims professionals have limited visibility into CBD use, and as the popularity of these products continues to grow, clinical science could potentially reveal significant concern that payers may need to take note of.

Tags: CBD, marijuana, cannabidiol, FDA