Biologic drugs have changed the face of psoriasis treatment but with each passing year the warnings labels have expanded to include more possible infections that can be linked to tumor necrosis factor-alpha (TNF-α) blocker use. Few people realize that the biologics approved for the treatment of psoriasis are indicated for people with psoriasis who are candidates for phototherapy. Litigation has ensued over the biologics adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), known as TNF-α inhibitors, because of cases of lupus, squamous cell cancer (SCC), histoplasmosis and coccidioidomycosis. While the biologic ustekinumab (Stelara), an interleukin (IL)12/IL23 inhibitor, has not engendered litigation, it seems prudent to test for potential serious infections before starting patients on the medication.
Monitoring of psoriasis patients on biologics has been discussed comprehensively.1 Nevertheless, dermatologists should be on guard for sources of litigation that involve biologics. This article will review cases that I have been able to identify in Lexis and a Google search to provide dermatologists with a sense of the litigation climate for the use of these therapies.
For the treatment of psoriasis, the package inserts indicate that the biologics are for patients who are candidates for other systemic agents (eg, methotrexate) or phototherapy. Adalimumab is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.2 Adalmumab’s package insert states it should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Etanercept is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.3 Infliximab is indicated for the treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. Infliximab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.4 Ustekinumab is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.5
Black box warnings are included on the labeling for adalimumab, etanercept and infliximab. Ustekinumab5 does not have any black box warning; nevertheless, I check patients taking ustekinumab for the presence of tuberculosis (TB) either with a purified protein derivative or a QuantiFERON-TB Gold test and an IgG and IgM test for histoplasmosis, coccidioidomycosis, Listeria and Legionella. The only test required is a TB test and that is often requested on prior authorization of biologics. I test all patients who I put on TNF-α inhibitors for TB. I check liver function tests and do a complete blood cell count before starting therapy. I repeat these tests annually. I also do not put patients on TNF-α inhibitors who have a family or personal history of lupus, lymphoma or multiple sclerosis.
Because there is increase risk of SCC with TNF-α inhibitors, they should be used with caution in patients who might be predisposed to the development of SCC. These include patients with a history of SCC, actinic keratosis and smokers who are already at an increase risk for oral cancers.
Adalimumab and SCC
Usually the litigation is brought against the drugmaker rather than the dermatologist as (1) many dermatologists have patients sign a form listing the risks of TNF-α inhibitors; and (2) the drugmaker is a much deeper pocket than the dermatologist.
Plaintiff Cynthia DiBartolo (“DiBartolo” or “plaintiff”)6 brought an action against defendant Abbott Laboratories (“Abbott” or “defendant”) to recover for injuries she allegedly suffered as a result of her use of defendant’s drug adalimumab to treat her psoriasis. After treatment with adalimumab for approximately 6 months, plaintiff was diagnosed with non-melanoma skin cancer, specifically SCC of the tongue and underwent 2 surgeries that have allegedly left her with permanent disabilities.
In her First Amended Complaint (the “amended complaint”), filed on May 8, 2012, DiBartolo asserted causes of action sounding in strict liability, negligence and breach of warranty based on theories of design defect, failure to warn and misrepresentation. This means she claimed adalimumab as an inherently defective product. Such causes of action are common when a defendant sues regarding what they think is a defective product that has caused them harm.
Abbott filed a motion to dismiss plaintiff’s amended complaint on May 25, 2012. DiBartolo filed her response to Abbott’s motion to dismiss on June 15, 2012, and Abbott filed its reply in support of its motion to dismiss plaintiff’s amended complaint on June 29, 2012. Abbott’s motion was granted to the extent that plaintiff alleges strict liability design defect, negligent design defect, strict liability misrepresentation, negligent misrepresentation and breach of express warranty as the FDA had approved the product and had been used in millions of people without incident.
Because DiBartolo has already filed one amended complaint and has not demonstrated good cause why the Court should grant DiBartolo leave to file a second amended complaint, DiBartolo’s claims were dismissed with prejudice to the extent stated above. Abbott’s motion was denied to the extent that DiBartolo alleges causes of action based on strict liability failure to warn, negligent failure to warn and breach of implied warranty. The case is ongoing.
Adalimumab and Coccidioidomycosis
A 69-year-old Tennessee man, Frederick Delano, filed a product liability lawsuit alleging he developed coccidioidomycosis as a result of side effects of adalimumab. The adalimumab infection lawsuit was filed in US District Court for the Western District of Tennessee against Abbott according to a report published on June 14, 2011.7
The complaint claims that Abbott failed to adequately warn consumers in a timely manner that the arthritis drug could cause fungal infections. According to an FDA warning, people living in the Mississippi and Ohio River Valleys were at greater risk than average for the fungal infections. At the time, the regulatory agency also warned that taking other drugs like immune suppressants could also increase the risk. Both of those factors applied to Delano. The lawsuit claims that the infection almost killed Delano. He is seeking compensatory and punitive damages against the company. This lawsuit is pending.
Adalimumab and Histoplasmosis
A Chicago jury ordered Abbott to pay $2.24 million in damages for a fungal infection from adalimumab; the verdict was published on May 14, 2013.8 This is the first case over the TNF-α inhibitor to go to trial in the United States. Milton Tietz filed the suit on behalf of his wife, Delores Tietz, who was diagnosed with histoplasmosis fungal infection in May 2010.
In the suit, Tietz alleged the fungal infection diagnosis did not come for months because Abbott did not warn doctors about the risk of problem. His wife died in 2012 of an unrelated heart attack. Following trial in Cook County Circuit Court, the jury found that Abbott was negligent and ruled that the drugmaker was to pay $2,244,063.20 in damages. However, the jury did not agree that the drug was a defective product.
Article continues on page 2
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Infliximab and Lupus
A jury in Texas ruled Centocor Inc. negligently and fraudulently failed to warn doctors and consumers about potential side effects of infliximab and must pay almost $20 million to Patricia Hamilton who claims she developed lupus as a result of using infliximab.9 In a 5-1 vote on December 13, 2006, the Nueces County Court at Law No. 4 jury found that Centocor committed fraud against Hamilton and that she and her husband were harmed as a result. The trial lasted 2½ weeks. The jury awarded Hamilton $3,365,908 in actual damages and $15 million in punitive damages. Thomas Hamilton was awarded $50,000 for loss of consortium and $1 million in punitive damages. The verdict was the first involving infliximab. Patricia was shown a videotape that she alleged overemphasized the benefits of infliximab, but intentionally omitted warnings about the adverse side effects she suffered. The case is pending on appeal.
Centocor argued to no avail in the trial court numerous defenses that included:
- The “learned intermediary” doctrine precludes the Hamiltons’ claims because Centocor adequately warned Patricia’s physicians
- The Hamiltons failed to present legally and factually sufficient evidence of causation
- The evidence of fraud by omission is legally and factually insufficient
- The Hamiltons cannot maintain a cause of action for implied misrepresentation, and their implied misrepresentation claims fail individually
- The Hamiltons failed to present expert testimony on the standard of care
- There is no cause of action for negligent misbranding
- The distribution of the videotape did not constitute negligent undertaking
- The evidence of future damages is legally and factually insufficient
- Thomas cannot recover on his derivative claims
- The judgment should be remitted as the trial court misapplied the punitive damages cap
Infliximab and Liver Failure
Although I have been unable to identify any cases involving liver failure and infliximab, the following data should lead dermatologists to do liver function tests while giving infliximab, which should be administered with low-dose methotrexate to prevent the development of antibodies to infliximab — a mouse protein.
Throughout 2011, there were at least 159 reports of severe liver injury with infliximab use, including 10 cases of liver failure.10 Use of medications containing acetaminophen were linked to 139 cases of liver injury, but 69 cases of liver failure, making acetaminophen the most frequently cited cause of acute liver failure among medications monitored by the group.
Conclusion
All patients should be offered phototherapy as a first-line treatment for psoriasis before prescribing a biologic. The offer of phototherapy and or other system drugs makes sense in view of black box warnings regarding these medications.
Biologics have been a boon for patients who have psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and juvenile rheumatoid arthritis, among others. However, TNF-α inhibitors have risks as well as benefits. It behooves the dermatologist to have a patient sign a form that outlines the risks of TNF-α inhibitors, to test for evidence of the infections included in the black box warnings and to closely follow patients who use these medications.
For example, I had a patient on etanercept who developed Mycobacterium avium complex pneumonia — the type of pneumonia more commonly associated with HIV before highly active retroviral agents were available. I saw the patient every month. When he told me he had a cough, I sent him to the hospital for a chest X-ray and sputum sample, which is how the diagnosis was made.
As I have demonstrated in the cases highlighted, side effects happen and sometimes side effects lead to litigation. Therefore, it is important for dermatologists to monitor their patients on biologics to ensure they are tolerating the drug.
The Right to Etanercept for a Prisoner
While this case is not a malpractice case, it is interesting to ponder who is entitled to a biologic. The Supreme Court has ruled that patients have a right to healthcare. It has not ruled that they are entitled to specific healthcare. In a number of states, Trustees have been appointed to ensure that patients with HIV get antiretroviral medications (eg, New York, California, among others).
Kevin Arnett,11 a former prisoner at the Bureau of Prisons Federal Correctional Complex in Terre Haute, Indiana, brought this Bivens action12 for cruel and unusual punishment under the Eighth Amendment against a number of prison officials for violations he alleged occurred during his 10-month stay. When Arnett arrived at the Terre Haute facility in November 2006, he was seen by Thomas Webster, MD, the prison’s clinical director. Arnett informed Dr. Webster that he had rheumatoid arthritis (RA) and asked for etanercept, the medication Arnett was taking before arriving at the prison and that had been successfully controlling his RA.
When Arnett entered prison, the doctors said they needed special permission to prescribe the medication because it was not on the prison’s formulary. Despite his numerous requests and a recommendation from his former physician, the proper medication was never prescribed, which he said caused escalating pain, severely swollen joints and possibly further joint damage. Among other rulings, the appellate court held that plaintiff had stated a claim against medical defendants for Eighth Amendment violations. He had a serious medical condition and his pleas for treatment and medication were ignored for 10 months. The medication request was made, but then languished. Even if the prison could not obtain the medication because it was not on the formulary, medical personnel had to explore alternative treatments that were available. The district court dismissed plaintiff’s claims against the prison’s doctors as they had no control over the formulary.
The case was taken up on appeal and the appeal court ruled that the district court was too hasty in dismissing plaintiff’s claims against the medical defendants, especially given its duty to construe pro se complaints liberally. However, a supervisory doctor could not be held liable in a Bivens action under respondeat superior (ie, he did what his superiors told him; etanercept was not on the formulary). The appellate court affirmed dismissal of the non-medical defendants on the pleadings, but found that plaintiff properly stated a claim against the medical defendants. However, the appellate court affirmed the district court’s grant of summary judgment in favor of a supervisory doctor. While this case is different from a malpractice case, it is important for dermatologists who practice in prisons to be aware of this case.
Dr. Scheinfeld graduated from Harvard Law School in 1989 and Yale Medical School in 1997. He is an assistant clinical professor in the Department of Dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: Dr. Scheinfeld has no conflicts of interest with any material in this column.
References
1. Lebwohl M, Bagel J, Gelfand JM, et al. From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis. J Am Acad Dermatol. 2008;58(1):94-105.
2. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2013.
3. Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.
4. Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.
5. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2012.
6. Dibartolo v Abbott Laboratories, 914 F. Supp. 2d 601(Southern District NY 2012).
7. Humira lawsuit filed by man with fungal infection. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-law suit-18807/. Accessed January 28, 2014.
8. Jackson I. Humira fungal infection lawsuit results in $2.2M jury verdict in first trial. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-lawsuit-verdict-46791/. Accessed January 28, 2014.
9. Hamilton, et al. v Centocor Inc., et al, No. 03-60526-4 (Texas Ct. at Law No. 4, Nueces Cty.). https://www.supreme.courts.state.tx.us/historical/2012/jun/100223.pdf Accessed January 31, 2014.
10. Kirk A. Remicade, acetaminophen linked to most reports of liver injury in 2011. AboutLawsuits.com website. https://www.aboutlawsuits.com/remicade-acetaminophen-liver-injury-re ports-28341/. Accessed January 28, 2014.
11. Arnett v Webster, No. 09-3280, United States Court of Appeals for the Seventh Circuit, 658 F.3d 742; 2011.
12. Bivens v. Six Unknown Named Agents of Fed. Bureau of Narcotics, 403 U.S. 388, 91 S. Ct. 1999, 29 L. Ed. 2d 619 (1971).
Biologic drugs have changed the face of psoriasis treatment but with each passing year the warnings labels have expanded to include more possible infections that can be linked to tumor necrosis factor-alpha (TNF-α) blocker use. Few people realize that the biologics approved for the treatment of psoriasis are indicated for people with psoriasis who are candidates for phototherapy. Litigation has ensued over the biologics adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), known as TNF-α inhibitors, because of cases of lupus, squamous cell cancer (SCC), histoplasmosis and coccidioidomycosis. While the biologic ustekinumab (Stelara), an interleukin (IL)12/IL23 inhibitor, has not engendered litigation, it seems prudent to test for potential serious infections before starting patients on the medication.
Monitoring of psoriasis patients on biologics has been discussed comprehensively.1 Nevertheless, dermatologists should be on guard for sources of litigation that involve biologics. This article will review cases that I have been able to identify in Lexis and a Google search to provide dermatologists with a sense of the litigation climate for the use of these therapies.
For the treatment of psoriasis, the package inserts indicate that the biologics are for patients who are candidates for other systemic agents (eg, methotrexate) or phototherapy. Adalimumab is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.2 Adalmumab’s package insert states it should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Etanercept is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.3 Infliximab is indicated for the treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. Infliximab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.4 Ustekinumab is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.5
Black box warnings are included on the labeling for adalimumab, etanercept and infliximab. Ustekinumab5 does not have any black box warning; nevertheless, I check patients taking ustekinumab for the presence of tuberculosis (TB) either with a purified protein derivative or a QuantiFERON-TB Gold test and an IgG and IgM test for histoplasmosis, coccidioidomycosis, Listeria and Legionella. The only test required is a TB test and that is often requested on prior authorization of biologics. I test all patients who I put on TNF-α inhibitors for TB. I check liver function tests and do a complete blood cell count before starting therapy. I repeat these tests annually. I also do not put patients on TNF-α inhibitors who have a family or personal history of lupus, lymphoma or multiple sclerosis.
Because there is increase risk of SCC with TNF-α inhibitors, they should be used with caution in patients who might be predisposed to the development of SCC. These include patients with a history of SCC, actinic keratosis and smokers who are already at an increase risk for oral cancers.
Adalimumab and SCC
Usually the litigation is brought against the drugmaker rather than the dermatologist as (1) many dermatologists have patients sign a form listing the risks of TNF-α inhibitors; and (2) the drugmaker is a much deeper pocket than the dermatologist.
Plaintiff Cynthia DiBartolo (“DiBartolo” or “plaintiff”)6 brought an action against defendant Abbott Laboratories (“Abbott” or “defendant”) to recover for injuries she allegedly suffered as a result of her use of defendant’s drug adalimumab to treat her psoriasis. After treatment with adalimumab for approximately 6 months, plaintiff was diagnosed with non-melanoma skin cancer, specifically SCC of the tongue and underwent 2 surgeries that have allegedly left her with permanent disabilities.
In her First Amended Complaint (the “amended complaint”), filed on May 8, 2012, DiBartolo asserted causes of action sounding in strict liability, negligence and breach of warranty based on theories of design defect, failure to warn and misrepresentation. This means she claimed adalimumab as an inherently defective product. Such causes of action are common when a defendant sues regarding what they think is a defective product that has caused them harm.
Abbott filed a motion to dismiss plaintiff’s amended complaint on May 25, 2012. DiBartolo filed her response to Abbott’s motion to dismiss on June 15, 2012, and Abbott filed its reply in support of its motion to dismiss plaintiff’s amended complaint on June 29, 2012. Abbott’s motion was granted to the extent that plaintiff alleges strict liability design defect, negligent design defect, strict liability misrepresentation, negligent misrepresentation and breach of express warranty as the FDA had approved the product and had been used in millions of people without incident.
Because DiBartolo has already filed one amended complaint and has not demonstrated good cause why the Court should grant DiBartolo leave to file a second amended complaint, DiBartolo’s claims were dismissed with prejudice to the extent stated above. Abbott’s motion was denied to the extent that DiBartolo alleges causes of action based on strict liability failure to warn, negligent failure to warn and breach of implied warranty. The case is ongoing.
Adalimumab and Coccidioidomycosis
A 69-year-old Tennessee man, Frederick Delano, filed a product liability lawsuit alleging he developed coccidioidomycosis as a result of side effects of adalimumab. The adalimumab infection lawsuit was filed in US District Court for the Western District of Tennessee against Abbott according to a report published on June 14, 2011.7
The complaint claims that Abbott failed to adequately warn consumers in a timely manner that the arthritis drug could cause fungal infections. According to an FDA warning, people living in the Mississippi and Ohio River Valleys were at greater risk than average for the fungal infections. At the time, the regulatory agency also warned that taking other drugs like immune suppressants could also increase the risk. Both of those factors applied to Delano. The lawsuit claims that the infection almost killed Delano. He is seeking compensatory and punitive damages against the company. This lawsuit is pending.
Adalimumab and Histoplasmosis
A Chicago jury ordered Abbott to pay $2.24 million in damages for a fungal infection from adalimumab; the verdict was published on May 14, 2013.8 This is the first case over the TNF-α inhibitor to go to trial in the United States. Milton Tietz filed the suit on behalf of his wife, Delores Tietz, who was diagnosed with histoplasmosis fungal infection in May 2010.
In the suit, Tietz alleged the fungal infection diagnosis did not come for months because Abbott did not warn doctors about the risk of problem. His wife died in 2012 of an unrelated heart attack. Following trial in Cook County Circuit Court, the jury found that Abbott was negligent and ruled that the drugmaker was to pay $2,244,063.20 in damages. However, the jury did not agree that the drug was a defective product.
Article continues on page 2
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Infliximab and Lupus
A jury in Texas ruled Centocor Inc. negligently and fraudulently failed to warn doctors and consumers about potential side effects of infliximab and must pay almost $20 million to Patricia Hamilton who claims she developed lupus as a result of using infliximab.9 In a 5-1 vote on December 13, 2006, the Nueces County Court at Law No. 4 jury found that Centocor committed fraud against Hamilton and that she and her husband were harmed as a result. The trial lasted 2½ weeks. The jury awarded Hamilton $3,365,908 in actual damages and $15 million in punitive damages. Thomas Hamilton was awarded $50,000 for loss of consortium and $1 million in punitive damages. The verdict was the first involving infliximab. Patricia was shown a videotape that she alleged overemphasized the benefits of infliximab, but intentionally omitted warnings about the adverse side effects she suffered. The case is pending on appeal.
Centocor argued to no avail in the trial court numerous defenses that included:
- The “learned intermediary” doctrine precludes the Hamiltons’ claims because Centocor adequately warned Patricia’s physicians
- The Hamiltons failed to present legally and factually sufficient evidence of causation
- The evidence of fraud by omission is legally and factually insufficient
- The Hamiltons cannot maintain a cause of action for implied misrepresentation, and their implied misrepresentation claims fail individually
- The Hamiltons failed to present expert testimony on the standard of care
- There is no cause of action for negligent misbranding
- The distribution of the videotape did not constitute negligent undertaking
- The evidence of future damages is legally and factually insufficient
- Thomas cannot recover on his derivative claims
- The judgment should be remitted as the trial court misapplied the punitive damages cap
Infliximab and Liver Failure
Although I have been unable to identify any cases involving liver failure and infliximab, the following data should lead dermatologists to do liver function tests while giving infliximab, which should be administered with low-dose methotrexate to prevent the development of antibodies to infliximab — a mouse protein.
Throughout 2011, there were at least 159 reports of severe liver injury with infliximab use, including 10 cases of liver failure.10 Use of medications containing acetaminophen were linked to 139 cases of liver injury, but 69 cases of liver failure, making acetaminophen the most frequently cited cause of acute liver failure among medications monitored by the group.
Conclusion
All patients should be offered phototherapy as a first-line treatment for psoriasis before prescribing a biologic. The offer of phototherapy and or other system drugs makes sense in view of black box warnings regarding these medications.
Biologics have been a boon for patients who have psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and juvenile rheumatoid arthritis, among others. However, TNF-α inhibitors have risks as well as benefits. It behooves the dermatologist to have a patient sign a form that outlines the risks of TNF-α inhibitors, to test for evidence of the infections included in the black box warnings and to closely follow patients who use these medications.
For example, I had a patient on etanercept who developed Mycobacterium avium complex pneumonia — the type of pneumonia more commonly associated with HIV before highly active retroviral agents were available. I saw the patient every month. When he told me he had a cough, I sent him to the hospital for a chest X-ray and sputum sample, which is how the diagnosis was made.
As I have demonstrated in the cases highlighted, side effects happen and sometimes side effects lead to litigation. Therefore, it is important for dermatologists to monitor their patients on biologics to ensure they are tolerating the drug.
The Right to Etanercept for a Prisoner
While this case is not a malpractice case, it is interesting to ponder who is entitled to a biologic. The Supreme Court has ruled that patients have a right to healthcare. It has not ruled that they are entitled to specific healthcare. In a number of states, Trustees have been appointed to ensure that patients with HIV get antiretroviral medications (eg, New York, California, among others).
Kevin Arnett,11 a former prisoner at the Bureau of Prisons Federal Correctional Complex in Terre Haute, Indiana, brought this Bivens action12 for cruel and unusual punishment under the Eighth Amendment against a number of prison officials for violations he alleged occurred during his 10-month stay. When Arnett arrived at the Terre Haute facility in November 2006, he was seen by Thomas Webster, MD, the prison’s clinical director. Arnett informed Dr. Webster that he had rheumatoid arthritis (RA) and asked for etanercept, the medication Arnett was taking before arriving at the prison and that had been successfully controlling his RA.
When Arnett entered prison, the doctors said they needed special permission to prescribe the medication because it was not on the prison’s formulary. Despite his numerous requests and a recommendation from his former physician, the proper medication was never prescribed, which he said caused escalating pain, severely swollen joints and possibly further joint damage. Among other rulings, the appellate court held that plaintiff had stated a claim against medical defendants for Eighth Amendment violations. He had a serious medical condition and his pleas for treatment and medication were ignored for 10 months. The medication request was made, but then languished. Even if the prison could not obtain the medication because it was not on the formulary, medical personnel had to explore alternative treatments that were available. The district court dismissed plaintiff’s claims against the prison’s doctors as they had no control over the formulary.
The case was taken up on appeal and the appeal court ruled that the district court was too hasty in dismissing plaintiff’s claims against the medical defendants, especially given its duty to construe pro se complaints liberally. However, a supervisory doctor could not be held liable in a Bivens action under respondeat superior (ie, he did what his superiors told him; etanercept was not on the formulary). The appellate court affirmed dismissal of the non-medical defendants on the pleadings, but found that plaintiff properly stated a claim against the medical defendants. However, the appellate court affirmed the district court’s grant of summary judgment in favor of a supervisory doctor. While this case is different from a malpractice case, it is important for dermatologists who practice in prisons to be aware of this case.
Dr. Scheinfeld graduated from Harvard Law School in 1989 and Yale Medical School in 1997. He is an assistant clinical professor in the Department of Dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: Dr. Scheinfeld has no conflicts of interest with any material in this column.
References
1. Lebwohl M, Bagel J, Gelfand JM, et al. From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis. J Am Acad Dermatol. 2008;58(1):94-105.
2. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2013.
3. Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.
4. Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.
5. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2012.
6. Dibartolo v Abbott Laboratories, 914 F. Supp. 2d 601(Southern District NY 2012).
7. Humira lawsuit filed by man with fungal infection. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-law suit-18807/. Accessed January 28, 2014.
8. Jackson I. Humira fungal infection lawsuit results in $2.2M jury verdict in first trial. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-lawsuit-verdict-46791/. Accessed January 28, 2014.
9. Hamilton, et al. v Centocor Inc., et al, No. 03-60526-4 (Texas Ct. at Law No. 4, Nueces Cty.). https://www.supreme.courts.state.tx.us/historical/2012/jun/100223.pdf Accessed January 31, 2014.
10. Kirk A. Remicade, acetaminophen linked to most reports of liver injury in 2011. AboutLawsuits.com website. https://www.aboutlawsuits.com/remicade-acetaminophen-liver-injury-re ports-28341/. Accessed January 28, 2014.
11. Arnett v Webster, No. 09-3280, United States Court of Appeals for the Seventh Circuit, 658 F.3d 742; 2011.
12. Bivens v. Six Unknown Named Agents of Fed. Bureau of Narcotics, 403 U.S. 388, 91 S. Ct. 1999, 29 L. Ed. 2d 619 (1971).
Biologic drugs have changed the face of psoriasis treatment but with each passing year the warnings labels have expanded to include more possible infections that can be linked to tumor necrosis factor-alpha (TNF-α) blocker use. Few people realize that the biologics approved for the treatment of psoriasis are indicated for people with psoriasis who are candidates for phototherapy. Litigation has ensued over the biologics adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), known as TNF-α inhibitors, because of cases of lupus, squamous cell cancer (SCC), histoplasmosis and coccidioidomycosis. While the biologic ustekinumab (Stelara), an interleukin (IL)12/IL23 inhibitor, has not engendered litigation, it seems prudent to test for potential serious infections before starting patients on the medication.
Monitoring of psoriasis patients on biologics has been discussed comprehensively.1 Nevertheless, dermatologists should be on guard for sources of litigation that involve biologics. This article will review cases that I have been able to identify in Lexis and a Google search to provide dermatologists with a sense of the litigation climate for the use of these therapies.
For the treatment of psoriasis, the package inserts indicate that the biologics are for patients who are candidates for other systemic agents (eg, methotrexate) or phototherapy. Adalimumab is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate.2 Adalmumab’s package insert states it should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician. Etanercept is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.3 Infliximab is indicated for the treatment of adult patients with chronic severe (ie, extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. Infliximab should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.4 Ustekinumab is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.5
Black box warnings are included on the labeling for adalimumab, etanercept and infliximab. Ustekinumab5 does not have any black box warning; nevertheless, I check patients taking ustekinumab for the presence of tuberculosis (TB) either with a purified protein derivative or a QuantiFERON-TB Gold test and an IgG and IgM test for histoplasmosis, coccidioidomycosis, Listeria and Legionella. The only test required is a TB test and that is often requested on prior authorization of biologics. I test all patients who I put on TNF-α inhibitors for TB. I check liver function tests and do a complete blood cell count before starting therapy. I repeat these tests annually. I also do not put patients on TNF-α inhibitors who have a family or personal history of lupus, lymphoma or multiple sclerosis.
Because there is increase risk of SCC with TNF-α inhibitors, they should be used with caution in patients who might be predisposed to the development of SCC. These include patients with a history of SCC, actinic keratosis and smokers who are already at an increase risk for oral cancers.
Adalimumab and SCC
Usually the litigation is brought against the drugmaker rather than the dermatologist as (1) many dermatologists have patients sign a form listing the risks of TNF-α inhibitors; and (2) the drugmaker is a much deeper pocket than the dermatologist.
Plaintiff Cynthia DiBartolo (“DiBartolo” or “plaintiff”)6 brought an action against defendant Abbott Laboratories (“Abbott” or “defendant”) to recover for injuries she allegedly suffered as a result of her use of defendant’s drug adalimumab to treat her psoriasis. After treatment with adalimumab for approximately 6 months, plaintiff was diagnosed with non-melanoma skin cancer, specifically SCC of the tongue and underwent 2 surgeries that have allegedly left her with permanent disabilities.
In her First Amended Complaint (the “amended complaint”), filed on May 8, 2012, DiBartolo asserted causes of action sounding in strict liability, negligence and breach of warranty based on theories of design defect, failure to warn and misrepresentation. This means she claimed adalimumab as an inherently defective product. Such causes of action are common when a defendant sues regarding what they think is a defective product that has caused them harm.
Abbott filed a motion to dismiss plaintiff’s amended complaint on May 25, 2012. DiBartolo filed her response to Abbott’s motion to dismiss on June 15, 2012, and Abbott filed its reply in support of its motion to dismiss plaintiff’s amended complaint on June 29, 2012. Abbott’s motion was granted to the extent that plaintiff alleges strict liability design defect, negligent design defect, strict liability misrepresentation, negligent misrepresentation and breach of express warranty as the FDA had approved the product and had been used in millions of people without incident.
Because DiBartolo has already filed one amended complaint and has not demonstrated good cause why the Court should grant DiBartolo leave to file a second amended complaint, DiBartolo’s claims were dismissed with prejudice to the extent stated above. Abbott’s motion was denied to the extent that DiBartolo alleges causes of action based on strict liability failure to warn, negligent failure to warn and breach of implied warranty. The case is ongoing.
Adalimumab and Coccidioidomycosis
A 69-year-old Tennessee man, Frederick Delano, filed a product liability lawsuit alleging he developed coccidioidomycosis as a result of side effects of adalimumab. The adalimumab infection lawsuit was filed in US District Court for the Western District of Tennessee against Abbott according to a report published on June 14, 2011.7
The complaint claims that Abbott failed to adequately warn consumers in a timely manner that the arthritis drug could cause fungal infections. According to an FDA warning, people living in the Mississippi and Ohio River Valleys were at greater risk than average for the fungal infections. At the time, the regulatory agency also warned that taking other drugs like immune suppressants could also increase the risk. Both of those factors applied to Delano. The lawsuit claims that the infection almost killed Delano. He is seeking compensatory and punitive damages against the company. This lawsuit is pending.
Adalimumab and Histoplasmosis
A Chicago jury ordered Abbott to pay $2.24 million in damages for a fungal infection from adalimumab; the verdict was published on May 14, 2013.8 This is the first case over the TNF-α inhibitor to go to trial in the United States. Milton Tietz filed the suit on behalf of his wife, Delores Tietz, who was diagnosed with histoplasmosis fungal infection in May 2010.
In the suit, Tietz alleged the fungal infection diagnosis did not come for months because Abbott did not warn doctors about the risk of problem. His wife died in 2012 of an unrelated heart attack. Following trial in Cook County Circuit Court, the jury found that Abbott was negligent and ruled that the drugmaker was to pay $2,244,063.20 in damages. However, the jury did not agree that the drug was a defective product.
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Infliximab and Lupus
A jury in Texas ruled Centocor Inc. negligently and fraudulently failed to warn doctors and consumers about potential side effects of infliximab and must pay almost $20 million to Patricia Hamilton who claims she developed lupus as a result of using infliximab.9 In a 5-1 vote on December 13, 2006, the Nueces County Court at Law No. 4 jury found that Centocor committed fraud against Hamilton and that she and her husband were harmed as a result. The trial lasted 2½ weeks. The jury awarded Hamilton $3,365,908 in actual damages and $15 million in punitive damages. Thomas Hamilton was awarded $50,000 for loss of consortium and $1 million in punitive damages. The verdict was the first involving infliximab. Patricia was shown a videotape that she alleged overemphasized the benefits of infliximab, but intentionally omitted warnings about the adverse side effects she suffered. The case is pending on appeal.
Centocor argued to no avail in the trial court numerous defenses that included:
- The “learned intermediary” doctrine precludes the Hamiltons’ claims because Centocor adequately warned Patricia’s physicians
- The Hamiltons failed to present legally and factually sufficient evidence of causation
- The evidence of fraud by omission is legally and factually insufficient
- The Hamiltons cannot maintain a cause of action for implied misrepresentation, and their implied misrepresentation claims fail individually
- The Hamiltons failed to present expert testimony on the standard of care
- There is no cause of action for negligent misbranding
- The distribution of the videotape did not constitute negligent undertaking
- The evidence of future damages is legally and factually insufficient
- Thomas cannot recover on his derivative claims
- The judgment should be remitted as the trial court misapplied the punitive damages cap
Infliximab and Liver Failure
Although I have been unable to identify any cases involving liver failure and infliximab, the following data should lead dermatologists to do liver function tests while giving infliximab, which should be administered with low-dose methotrexate to prevent the development of antibodies to infliximab — a mouse protein.
Throughout 2011, there were at least 159 reports of severe liver injury with infliximab use, including 10 cases of liver failure.10 Use of medications containing acetaminophen were linked to 139 cases of liver injury, but 69 cases of liver failure, making acetaminophen the most frequently cited cause of acute liver failure among medications monitored by the group.
Conclusion
All patients should be offered phototherapy as a first-line treatment for psoriasis before prescribing a biologic. The offer of phototherapy and or other system drugs makes sense in view of black box warnings regarding these medications.
Biologics have been a boon for patients who have psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis and juvenile rheumatoid arthritis, among others. However, TNF-α inhibitors have risks as well as benefits. It behooves the dermatologist to have a patient sign a form that outlines the risks of TNF-α inhibitors, to test for evidence of the infections included in the black box warnings and to closely follow patients who use these medications.
For example, I had a patient on etanercept who developed Mycobacterium avium complex pneumonia — the type of pneumonia more commonly associated with HIV before highly active retroviral agents were available. I saw the patient every month. When he told me he had a cough, I sent him to the hospital for a chest X-ray and sputum sample, which is how the diagnosis was made.
As I have demonstrated in the cases highlighted, side effects happen and sometimes side effects lead to litigation. Therefore, it is important for dermatologists to monitor their patients on biologics to ensure they are tolerating the drug.
The Right to Etanercept for a Prisoner
While this case is not a malpractice case, it is interesting to ponder who is entitled to a biologic. The Supreme Court has ruled that patients have a right to healthcare. It has not ruled that they are entitled to specific healthcare. In a number of states, Trustees have been appointed to ensure that patients with HIV get antiretroviral medications (eg, New York, California, among others).
Kevin Arnett,11 a former prisoner at the Bureau of Prisons Federal Correctional Complex in Terre Haute, Indiana, brought this Bivens action12 for cruel and unusual punishment under the Eighth Amendment against a number of prison officials for violations he alleged occurred during his 10-month stay. When Arnett arrived at the Terre Haute facility in November 2006, he was seen by Thomas Webster, MD, the prison’s clinical director. Arnett informed Dr. Webster that he had rheumatoid arthritis (RA) and asked for etanercept, the medication Arnett was taking before arriving at the prison and that had been successfully controlling his RA.
When Arnett entered prison, the doctors said they needed special permission to prescribe the medication because it was not on the prison’s formulary. Despite his numerous requests and a recommendation from his former physician, the proper medication was never prescribed, which he said caused escalating pain, severely swollen joints and possibly further joint damage. Among other rulings, the appellate court held that plaintiff had stated a claim against medical defendants for Eighth Amendment violations. He had a serious medical condition and his pleas for treatment and medication were ignored for 10 months. The medication request was made, but then languished. Even if the prison could not obtain the medication because it was not on the formulary, medical personnel had to explore alternative treatments that were available. The district court dismissed plaintiff’s claims against the prison’s doctors as they had no control over the formulary.
The case was taken up on appeal and the appeal court ruled that the district court was too hasty in dismissing plaintiff’s claims against the medical defendants, especially given its duty to construe pro se complaints liberally. However, a supervisory doctor could not be held liable in a Bivens action under respondeat superior (ie, he did what his superiors told him; etanercept was not on the formulary). The appellate court affirmed dismissal of the non-medical defendants on the pleadings, but found that plaintiff properly stated a claim against the medical defendants. However, the appellate court affirmed the district court’s grant of summary judgment in favor of a supervisory doctor. While this case is different from a malpractice case, it is important for dermatologists who practice in prisons to be aware of this case.
Dr. Scheinfeld graduated from Harvard Law School in 1989 and Yale Medical School in 1997. He is an assistant clinical professor in the Department of Dermatology at Weill Cornell Medical College in New York, NY.
Disclosure: Dr. Scheinfeld has no conflicts of interest with any material in this column.
References
1. Lebwohl M, Bagel J, Gelfand JM, et al. From the Medical Board of the National Psoriasis Foundation: monitoring and vaccinations in patients treated with biologics for psoriasis. J Am Acad Dermatol. 2008;58(1):94-105.
2. Humira [package insert]. North Chicago, IL: AbbVie Inc; 2013.
3. Enbrel [package insert]. Thousand Oaks, CA: Amgen Inc; 2013.
4. Remicade [package insert]. Horsham, PA: Janssen Biotech, Inc; 2013.
5. Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; 2012.
6. Dibartolo v Abbott Laboratories, 914 F. Supp. 2d 601(Southern District NY 2012).
7. Humira lawsuit filed by man with fungal infection. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-law suit-18807/. Accessed January 28, 2014.
8. Jackson I. Humira fungal infection lawsuit results in $2.2M jury verdict in first trial. AboutLawsuits.com website. https://www.aboutlawsuits.com/humira-fungal-infection-lawsuit-verdict-46791/. Accessed January 28, 2014.
9. Hamilton, et al. v Centocor Inc., et al, No. 03-60526-4 (Texas Ct. at Law No. 4, Nueces Cty.). https://www.supreme.courts.state.tx.us/historical/2012/jun/100223.pdf Accessed January 31, 2014.
10. Kirk A. Remicade, acetaminophen linked to most reports of liver injury in 2011. AboutLawsuits.com website. https://www.aboutlawsuits.com/remicade-acetaminophen-liver-injury-re ports-28341/. Accessed January 28, 2014.
11. Arnett v Webster, No. 09-3280, United States Court of Appeals for the Seventh Circuit, 658 F.3d 742; 2011.
12. Bivens v. Six Unknown Named Agents of Fed. Bureau of Narcotics, 403 U.S. 388, 91 S. Ct. 1999, 29 L. Ed. 2d 619 (1971).
