Case law on ulcerative colitis, IBD, suicide and RoAccutane

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Summary :

It seems very likely that a major part of the side effects, including "depressions"
and other "psychological disorders" post Isotretinoin (roaccutane), are only a consequence
strongly correlated with tangible, iatrogenic, physical and organic disorders, with late
diagnosis, because they develop silently without initial symptoms, with a latency period, of
a primary physiological need, essential for survival, nutrition and digestion: Chronic
Inflammatory Bowel Diseases (IBD).
Knowing that once a psychiatric diagnosis has been made, the medical profession
(which is the primary source of stigmatization), among other institutions, will take somatic
complaints less into account, this also explaining the gap between the number of postroaccutane patients and their current non-recognition, despite the controversy
surrounding this "medication".
Nearly 4 decades have been devoted by the scientific community and drug safety regulatory agencies around the
world to studying the link between roaccutane and psychiatric disorders, and very recently the link between
roaccutane and sexual disorders.

This is contrary to the proportions of the major categories of the global
pharmacovigilance signal, and particularly to the US FDA pharmacovigilance
phase 4 data from: https://www-ehealthme-com.translate.goog/drug/
accutane/side-effects/?
_x_tr_sl=auto&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp , which clearly shows that IBDs are
more common than "depressions", and that this trend increases the more time passes
after taking roaccutane (latency period of their onset). This
IBD onset latency also corroborates delayed onset toxicity which
could also be observed for all other side effects of roaccutane.
Furthermore, the case law of the wave of lawsuits won by the pharmaceutical
laboratory due to procedural defects, or shifting the blame to the prescribing doctors, or
proposals to pay the exact amount of the damage, according to the legislation, to the
plaintiff, at the initiative of the laboratory, in return for the legal non-recognition of said
damage;
These case laws therefore also contain elements which demonstrate that no clinical
epidemiological study on the link between MICI and Isotretinoin has ever been conducted.
large scale, despite their higher reporting than “psychiatric disorders” in pharmacovigilance.
These case laws refer to internal laboratory studies stipulating such an association,
including challenge-rechallenge studies, which irrefutably demonstrate this link,
because this type of study constitutes unequivocal proof of a cause-and-effect link between
Isotretinoin and IBD, with an observed trigger latency time.
It seems that these challenge-dechallenge-rechallenge studies have never been
replicated either.
Added to this is the fact that IBD progresses in flare-ups and is often diagnosed late in
relation to its onset.
The causes and explanations of lifelong disabilities due to roaccutane being multifactorial,
there is now a pressing need to focus on the main factor of its iatrogenesis, and to
study epidemiologically the occurrence of the disabling side effect.
more widespread and declared, IBD, and more particularly at the level of polymorphisms

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genetics encoding the regulation of the microbiota and the intestinal wall, as well as the point mutagenesis
that occur during and after taking isotretinoin (roaccutane). Epidemiological studies of correlations on the
proportion of "depressions" underpinned by these iatrogenic IBDs should also be conducted, in order
to discriminate from "depressions" produced by iatrogenic brain lesions.

Monitoring when prescribing the occurrence of gastrointestinal disorders would be
just as relevant as the monitoring of the occurrence of depressive disorders obtained recently in the United
Kingdom, given the equivalent proportions of these 2 subgroups in the pharmacovigilance signal (approximately
1/3 for each, or 2/3 for “depressions” and IBD).

Summary :
1) chronic inflammatory bowel disease (IBD), Roaccutane, “depression”
and “side effects”
2) Roaccutane trial history
2.1) jurisprudence of a roaccutane and IBD trial
2.2) jurisprudence of a roaccutane and “depression” trial

1) chronic inflammatory bowel diseases (IBD),
Roaccutane, “depression” and “side effects”:
“Inflammatory bowel disease (IBD): what is it?
IBD is characterized by areas of chronic inflammation of the digestive wall.
These pathologies manifest themselves through phases of activity of varying intensity, called flare-ups, which
alternate with periods of pause called “remission”.
The origin of these conditions is poorly understood. From a physiological point of view, one hypothesis
states that these pathologies could be due to an abnormal response of the intestinal immune defenses to the
bacterial flora in genetically predisposed individuals.[…]

Studies have uncovered many IBD susceptibility genes. These genes promote the onset of the disease but it
is not hereditary.
The role of environmental factors (diet, pollution, infection during childhood, excess hygiene, etc.) remains
somewhat unclear for the moment. The composition of the intestinal microbiota could influence these
diseases.
Excerpt from: https://www.frm.org/recherches-maladies-rares/maladies-inflammatorys-chroniques-de-lintestin/focus-mici-crohn

“Symptoms/Complications
Rectal bleeding is common and can be present in varying amounts. Blood is usually evident in and on the surface
of the stool. The second most common symptom is diarrhea, accompanied by cramping and abdominal pain.
Symptoms range in intensity from mild to severe. This may result in impaired

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red blood cells (anemia) if diarrhea and blood loss are severe. Constipation may also develop as the body struggles
to maintain normal bowel function.

Because ulcerative colitis is a systemic disease, it can affect other parts of the body and therefore cause extraintestinal
manifestations in some people, which include fever, eye or joint inflammation, mouth ulcers, or tender, inflamed
nodules on the shins.

If you have had ulcerative colitis for 10 to 15 years, you have a slightly higher risk of developing colorectal
cancer. Your doctor may recommend earlier screening for this condition than is typically recommended for the
general population.

Excerpt from: https://badgut.org/centre-information/sujets-de-aaz/colite-ulcereuse/?lang=fr

"The origin of depression and anxiety in patients with Inflammatory Bowel Disease (IBD) is not
adequately explained. People with IBD are at increased risk of developing anxiety or depression.
These emotional factors affect the way a person experiences, perceives and copes with the disease."

Excerpt from: https://crohnetcolite.ca/About-these-diseases/The-Journey-of-IBD/Mental-Health-and-Well-being/
MIIandmentalhealth
"As previously stated, fatigue is an integral part of the symptoms of depression. It is known that patients with IBD
frequently suffer from depression
and anxiety disorders. In the recent French BIRD study, we even found depressive signs in almost 50% and
pathological anxiety in 30% of them"
Excerpt from: https://www.afa.asso.fr/wp-content/uploads/2020/03/FATIGUE-ET-DEPRESSION.pdf

"Impaired sexual function is significantly more common in patients with IBD than in the general population in both
sexes. Associated factors in women are depression and in men lack of physical exercise and impaired
emotional functioning."
https://www.fmcgastro.org/breves-congres/jfhod-2017/les-entreprises-inflammatory-du-digestif-tube-sont-elles-alorigine-de-troubles-de-la-sexuxalite/

2) Roaccutane trial history:
"Thousands of people who have suffered from the side effects of Accutane have filed
lawsuits, claiming that the drug's manufacturer, Roche, failed to warn them of the drug's dangers. Most of
the litigation involved Crohn's disease and ulcerative colitis.

Historically, Accutane litigation has favored the manufacturer. Judges have dismissed the majority of lawsuits
and overturned jury verdicts that awarded millions of dollars to plaintiffs.

Excerpt from: https://www-drugwatch-com.translate.goog/accutane/lawsuits/?
_x_tr_sl=auto&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp
With the various appeals, the procedures generally lasted more than 10 years.

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"Roche Pharmaceuticals, also known as Hoffman La-Roche, was aware even before it launched the acne drug
Accutane that the acne drug could cause harmful side effects. Initially, birth defects were known to be caused by
Accutane, but soon many more injuries became evident, with Roche finally – and very belatedly – issuing an
Accutane recall in 2009. Of course, that was 27 years too late, since the drug was first introduced in 1982.

Indeed, when Roche invented Accutane to treat severe acne in 1972, it set it apart from the market because of
awareness of its risk of birth defects.
congenital defects. But Roche's own interests prevailed a decade later when it marketed and sold Accutane
as a "miracle" acne cure. Yes, it worked. But then the birth defects, predictably, started happening.

In 1984, the Food and Drug Administration made Roche put warnings about birth defects on the drug
label, and a year later, Roche also included warnings about seizures, nervousness, dizziness, depression,
insomnia, malaise, emotional lability, lethargy, drowsiness, and weakness. Could it get worse?

YES. And that’s what it did. It was wrong. Soon, Americans learned that Accutane caused not only
depression, but suicidal impulses—and even suicide itself. So in 1998, the FDA required more warnings for depression
and suicide, before adding violent behavior and aggression to the list.
years later.
But knowledge of some of Accutane's horrendous side effects was yet to come, when it was revealed that
Accutane could inflict lifelong gastrointestinal and digestive disorders such as inflammatory bowel
diseases (IBD) called ulcerative colitis and Crohn's disease. Both have hurt thousands of those who have
taken Accutane, and sometimes even led to colon removal surgery. Furthermore, these diseases have no
cure.
known.

Finally, Roche withdrew Accutane in 2009, but the damage had been done - and continues
to be felt by many patients."
Retrieved
from: https://web.archive.org/web/20130101053247/http://www.accutaneaction.com/Press/11032
4_more%20side%20effects.html

2.1) Case law of a roaccutane and IBD trial:
Excerpts from the translation of the case law of the victory of the appeal of the laboratory manufacturing
roaccutane, which was ordered to pay 9 million dollars to each of the two plaintiffs (KATHLEEN ROSSITTO v.
HOFFMAN-LA ROCHE INC
and RILEY DEAN WILKINSON v. HOFFMAN-LA ROCHE INC. And ROCHE LABORATORIES INC.)
Date: July 22, 2016
DOCKET NO. A-1236-13T1
A-1237-13T1 ) :
https://law-justia-com.translate.goog/cases/new-jersey/appellate-division-

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unpublished/2016/a1236-13.html?_x_tr_sl=en&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp
https://law.justia.com/cases/new-jersey/appellate-division-unpublished/2016/a1236-13.html
https://business.cch.com/plsd/RossittovHoffman-LaRoche.pdf
"Studies prior to the drug's FDA approval revealed dose-related cases of gastrointestinal bleeding in dogs treated
with the drug. (In an internal document from 1978, Roche noted a call from Dr.
FDA pharmacologist Manfred Hein, in which he expressed concern about gastrointestinal bleeding
observed in canine studies.)
Similarly, in a clinical study of Accutane conducted by Roche on 523 patients, 21.6%
of these (113 patients) suffered gastrointestinal side effects, mainly effects on the mucous membranes,
including effects such as increased thirst and appetite, nausea and anorexia, as well as more serious
gastrointestinal bleeding.

Five patients withdrew from the study because of undisclosed gastrointestinal effects, but no cases of IBD were
reported. Gastrointestinal symptoms, but not inflammatory bowel disease (IBD), were also reported in 34%
of patients in clinical trials taking a chemically similar drug (Vesanoid, the brand name for tretinoin), made
by Roche to treat leukemia.

[…] IBD refers to “several chronic, incurable diseases characterized by inflammation of the intestine. […] The
disease occurs when a trigger triggers an abnormal or exaggerated immune response, that is, an ongoing
inflammatory reaction.
IBD is primarily manifested by one of two diseases: ulcerative colitis and Crohn's disease. Ulcerative colitis, the
disease with which the plaintiffs were diagnosed, is "a chronic disease characterized by ulceration of the colon and
of the rectum.” Crohn’s disease is similar to ulcerative colitis in that it causes inflammation and ulcers, but it can
occur anywhere in the digestive tract, from the mouth to the anus. People with IBD typically experience
abdominal pain and frequent, often bloody stools, leading to fatigue, dehydration, anemia, fever, cramps,
and bloating.
Symptoms often wax and wane, but the disease is lifelong and there is no known cure. […]

There have been no post-marketing clinical trials to study whether Accutane use causes IBD. Such a
study is considered the “gold standard” for assessing causality, but would require a very large clinical
trial. […]

As part of the monitoring process, Roche collected data on adverse drug experiences or events through
its call center and through MedWatch, the FDA's voluntary reporting system. As required by 21 CFR 314.80(f),
Roche recorded the reports on an FDA form, listing among other information, a description of the event and
whether it improved after the patient stopped using Accutane and returned after restarting the drug
(called a "challenge"/"dechallenge"/"rechallenge").

From 1992 to 1998, Roche recorded several positive reports of IBD recurrence. Dr. Bess admitted that in some
cases, a single positive re-challenge may be

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important enough to warrant inclusion of the event on the label. […]
Roche reported that from 1982 to 1994, 104 cases of IBD and related syndromes were reported in
Accutane users, thirty-three of which were given a causality rating of "possibly" or "probably" related to
administration of the drug. […]

Based on this information, Dr. Henry Lefrancq, a physician at Roche, stated in an internal memo dated February
24, 1994: " It is reasonable to conclude from these
data that, in rare cases, ROACCUTANE may induce or worsen pre-existing colitis. Dr. Lefrancq explained
that it was reasonable to assume that Accutane has
"the same effect on the intestinal mucosa as [was observed] on other mucosa
of the body such as the oral or nasal mucosa." He added: "Since these reactions have always been reversible, the
colitis that can develop in a relatively small number of patients can just as well be considered reversible."

In another internal report from May 2003, Roche said that 159 reports of adverse events related to Accutane
exposure had been received from sources worldwide.
Sixty-four of these patients had Crohn's disease, the causality of which Roche assessed as "related" in twenty-seven
cases. The remainder were designated as unrelated or unknown, and twenty-nine had IBD (not otherwise
specified), the causality of which was assessed as related in thirteen cases and unknown in the remaining
sixteen cases. […] between 1 January and 30 June 1988 and concluded that "since introduction, ROCHE

Drug Safety has received 38 case reports of colitis [IBD] and proctitis in association with ROACCUTAN
treatment. » Twenty-two patients “recovered” after stopping the
Accutane treatment, but nine patients had persistent colitis or proctitis and one patient underwent "total
colectomy ." In another report dated November 16, 2000, Roche stated that "[i]sotretinoin has been shown to be
associated with
causally related to inflammatory bowel disease, including colitis." Later, in a January 2003 report, Dr. Daniel Reshef,
Roche's director of drug safety, said there was "a mean latency of events from the start of treatment"
to the onset of IBD symptoms "ranging from 23 to 1,219 days. […]

In May 2000, after all plaintiffs in this lawsuit had completed treatment, Roche amended the warnings section on
Accutane. It removed the word "temporarily" and added the following language about persistent IBD
symptoms.
Inflammatory bowel disease: Accutane has been associated with inflammatory bowel disease in patients without a
Accutane

history of bowel disorders. In some cases, symptoms have been reported to persist after stopping

treatment. Patients with abdominal pain, rectal bleeding, or severe diarrhea should
immediately stop Accutane (see ADVERSE REACTIONS: Gastrointestinal).
Despite the label's acknowledgement of an association, Roche's position at trial was that Accutane does not
cause IBD.
[…] although Accutane has a half-life of only about ten to twenty hours, it acts as a trigger, setting off an
inflammatory effect that leads to the latent development of Accutane-induced IBD. […] he
had become symptomatic about six to twelve months after stopping the drug, which was well
within the latency period […] he had been diagnosed with ulcerative colitis about fourteen months
after stopping

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taking Accutane, which was also fine in the drug's lag period . […]

According to Dr. Blume, given the generally accepted rates of underreporting by the
FDA, these reports may represent only one to ten percent of the true incidence of IBD in
Accutane patients. […]
The jury awarded Rossitto and Wilkinson an identical $9 million in compensatory
damages. Roche's appeal followed.
[…]Roche further argues that the plaintiffs have not presented sufficient evidence of a proximate
causal link. It argues that Rossitto's and Wilkinson's claims should be dismissed because their
respective doctors would have prescribed Accutane to them anyway, even if the 1984 label
had contained a stronger warning.
See Strumph v. Schering Corp., 256 N.J. Super. 309, 323-28 (App. Div. 1992) (Skillman, J.,
dissenting), revised in dissent, 133 N.J. 33 (1993).
[…]Under New Jersey law, failure to provide adequate warning cannot be the proximate cause
of an injury when there is an intervening cause, i.e., the physician failed to read the warning or
lacked independent knowledge of the risks. Perez, supra, 161 N.J., at p. 28. For dismissal of
the suit to be justified on this basis, the evidence must be clear and unequivocal. "Where the
plaintiffs' prescribing physicians testify unequivocally that they had full knowledge of the
dangers
associated with a drug and that neither that knowledge nor anything in the heightened
post-injury warnings provided by the manufacturer would have changed their decision to
prescribe it, the plaintiff has failed to demonstrate that inadequate warnings are a proximate
cause of injury and that there should be a verdict for the defendant." See Dreier, Keefe &
Katz, supra, 8:3-2, at 200 (emphasis added).
"Where such a statement is not unequivocal, the question is for the jury."
Ibid. ; see also Strumph, supra, 256 N.J. Super. at 328 (per Skillman J., dissenting)
(concluding that "a defendant drug manufacturer cannot be held liable for an alleged inadequate
warning where the only evidence on the issue of causation is the prescribing physician's
unequivocal testimony that his decision to prescribe the drug was unaffected by the
warning") (us
(let us emphasize).

[…]we therefore set aside the verdict on the basis of these two critical and
cumulative errors and remand for a new trial. […]
Roche further argues that the plaintiffs have not presented sufficient evidence of a proximate
causal link. It argues that Rossitto's and Wilkinson's claims should be dismissed because
their respective doctors would have prescribed Accutane to them anyway, even if the 1984
label had contained a stronger warning.
"Where such a statement is not unequivocal, the question is for the jury."
Ibid. ; see also Strumph, supra, 256 N.J. Super. at 328 (per Skillman J., dissenting)
(concluding that " a defendant drug manufacturer cannot be held liable for an
alleged inadequate warning where the only evidence on the issue of causation is the
prescribing physician's unequivocal testimony that his decision to prescribe the
drug was unaffected by the warning ")

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2.2) jurisprudence of a roaccutane and “depression” trial:
https://www-independent-ie.translate.goog/irish-news/13-years-after-my-son-died-its-great-toget-my-day-in-court/26663138.html?
_x_tr_sl=auto&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp
https://www-irishobserver-com.translate.goog/news/arid-20232556.html?
_x_tr_sl=auto&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp
"An Irish father fighting to prove that an acne drug led to his son's suicide has spearheaded
a real cultural shift in the EU towards transparency, the European Ombudsman has said."
"It took the tragedy of an Irish father whose son committed suicide after taking an antiacne medication, which led to depression and suicide. He spent about €1 million over 10
years trying to access the documentation, and he couldn't.
The London-based European Medicines Agency, which approves and monitors medicines in
the EU, receives information about suspected side effects of medicines from national
authorities and pharmaceutical companies.
Initially, they refused to give Mr Grant access to information about Roaccutane,
an accountant, arguing that it was necessary to protect business interests, but ultimately
followed the ombudsman's advice and disclosed the information."
"He described the MEPs running for the post as "tricky" and added that he hoped that
"whoever is elected will be able to provide convincing evidence of their
independence and impartiality in this role."

Judgment Liam Grant versus Roche product, May 7, 2008, Supreme Court of Ireland:
https://www.casemine.com/judgement/uk/5da029714653d058440f96c4#
https://www-casemine-com.translate.goog/judgement/uk/5da029714653d058440f96c4?
_x_tr_sl=auto&_x_tr_tl=fr&_x_tr_hl=fr&_x_tr_pto=wapp#

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