Questions and Answers on Remicade/FDA Action
May 19, 2006 (fda.gov)
Postmarketing Reviews (fda.gov 2008;1(2))
Humira - ny sikkerhetsinformasjon (legemiddelverket.no 31.7.2008)
FDA kräver skärpt varningstext på TNF-blockerare (lakemedelsvarlden.se 5.9.2008)
Pakningsvedlegg (fda.gov):
2-Deaths in Pfizer arthritis trial hurt shares
reuters.com 21.4.2011
* 4 patient deaths reported in Pfizer drug study
* Pfizer shares close down 3 percent
* Pfizer says one of four deaths found drug study-related (Adds Pfizer comment)
NEW YORK, April 21 (Reuters) - New data raising safety concerns for Pfizer Inc's (PFE.N) experimental arthritis drug sent its shares down 3 percent, while lifting shares of rival drugmaker Abbott Laboratories (ABT.N), analysts said.
Wells Fargo analyst Larry Biegelsen in a research report on Thursday said four deaths were seen in one late-stage study of tofacitinib, Pfizer's oral drug for rheumatoid arthritis, which has been considered a potential rival to Abbott's big-selling Humira.
It was not clear from a brief description of the study, called an abstract, that the drug caused the deaths, Biegelsen said. But the report of the fatalities spooked investors.
The abstract from a 792-patient study to be presented at a meeting of the European League against Rheumatism said four patients who had been taking the 10-milligram dose of the Pfizer drug had died, including one from heart failure.
Pfizer said in a statement late on Thursday that the investigator reported only one of the four deaths -- the case of respiratory failure -- as study-drug related.
The drugmaker also said that the mortality rate from all causes across its drug development program, including this study, is within the range of rates reported for all biologic therapies for rheumatoid arthritis. (...)
Clues to Why Rheumatoid Arthritis Drug Humira Fails Some Patients
health.yahoo.net 12.4.2011
TUESDAY, April 12 (HealthDay News) -- In a new study, close to a third of patients taking the arthritis drug Humira developed an immune system reaction to it that rendered it ineffective.
Researchers say the finding helps to explain why some people get relief from their rheumatoid arthritis symptoms while on Humira (adalimumab), which is made by Abbott Laboratories, while others gain little or no benefit. Humira belongs to a class of drugs known as biologics. (...)
Humira (adalimumab) injection
fda.gov/Safety/MedWatch 15.12.2009
BOXED WARNING
Malignancy
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member. (...)
Enbrel (etanercept)
fda.gov/Safety/MedWatch 15.12.2009
BOXED WARNING
Malignancy
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including Enbrel. (...)
Remicade (infliximab) for IV injection
BOXED WARNING
Malignancy
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including Remicade. (...)
Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi)
fda.gov/Safety/MedWatch 2009 (August 31)
FDA notified healthcare professionals that it has completed its analysis of tumor necrosis factor (TNF) blockers and has concluded that there is an increased risk of lymphoma and other cancers associated with the use of these drugs in children and adolescents. This new safety information is now being added to the Boxed Warning for these products. (...)
FDA: Arthritis Drugs Pose Cancer Risk to Children (FDA: Artritt-legemidler utgjør kreftrisiko for barn)
online.wsj.com 5.8.2009
WASHINGTON -- The Food and Drug Administration said Tuesday there's an increased risk of lymphoma and other cancers associated with the use of drugs like Remicade and Humira for children and adolescents.
The agency said a new cancer-related warning will be added to the boxed-warning that's already on the drugs, which are known as tumor necrosis factor, or TNF blockers.
The drugs, which also include Enbrel, Cimzia and Simponi, are approved to treat various immune system diseases including juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ankylosing spondylitis. (...)
Study Clears Gene Therapy in Death of Arthritis Patient
medpagetoday.com 8.7.2009
PRINCETON, N.J., July 8 -- The death of a young patient participating in a gene-therapy trial for a rheumatoid arthritis drug was most likely the result of another arthritis drug, adalimumab (Humira), and not the novel gene therapy agent, a new study found.
"The death of this young patient who was receiving multiple forms of TNF inhibitors highlights the risk of opportunistic infections in patients receiving such agents, and the importance of having a well-designed monitoring plan when a patient in a study becomes ill," Karen M. Frank, MD, of the University of Chicago Medical Center, and colleagues wrote in the July 9 issue of New England Journal of Medicine. (...)
(Anm: Investigation of the Cause of Death in a Gene-Therapy Trial. NEJM 2009;61:161-169 (July 9).)
Rheumatoid Arthritis Drugs Raise Shingles Risk (Legemidler mot revmatisk artritt øker risiko for helvetesild)
healthfinder.gov 18.2.2009
Older people and those also taking steroids are most vulnerable, study finds.
(SOURCES: Guy Fiocco, M.D., assistant professor, internal medicine, Texas A&M Health Science Center College of Medicine, and director, rheumatology, Scott & White, Temple, Texas; Anja Strangfeld, M.D., epidemiology unit, German Rheumatism Research Centre, Berlin; Feb. 18, 2009, Journal of the American Medical Association)
TUESDAY, Feb. 17 (HealthDay News) -- A class of medications used widely to treat rheumatoid arthritis and other autoimmune diseases might increase the risk of shingles, especially among older people and those who are also taking steroids.
But while the findings, appearing in the Feb. 18 issue of the Journal of the American Medical Association, might raise awareness of the potential complication among physicians and patients, some experts say it's unlikely to change how the drugs are used. (...)
FDA says ad for Abbott's Humira downplays risks
reuters.com 23.12.2008
WASHINGTON (Reuters) - An advertisement for Abbott Laboratories' Humira minimizes the arthritis drug's risks while suggesting it can treat a wider range of patients than it is approved to treat, the U.S. Food and Drug Administration said in a letter released on Tuesday.
The drug is cleared to treat certain patients with arthritis, psoriasis, Crohn's Disease or a form of arthritis called ankylosing spondylitis. (...)
Svårt hitta säkra testmodeller för biologiska läkemedel
lakemedelsvarlden.se 13.11.2008
De biologiska läkemedlen blir allt fler och utvecklingen går snabbt. Men det är svårt att hitta pålitliga metoder för att undersöka säkerheten med de nya preparaten. (...)
Som biologiska läkemedel räknas sådana vars aktiva substans har biologiskt ursprung. Många av dessa ingår i vanliga läkemedel som till exempel antikroppar, enzymer, interferoner och hormoner. Omkring 25 procent av alla läkemedel som 2006 godkändes av FDA och EMEA var biologiska.
Denna relativt nya läkemedelsgrupp har haft en enorm betydelse för flera behandlingar av bland annat autoimmuna sjukdomar och cancer. Monoklonala antikroppar registreras till exempel ett stort antal varje år. En utmaning med dessa är att det krävs andra metoder för att mäta renhet och mängd aktiv substans preparat.
- Vissa problem är förväntade, till exempel när man använder djurantikroppar i människa. Men även med adalimumab (Humira) som är en human antikropp drabbas upp till 16 procent av allergiska reaktioner, sade Nina Brenden från Astrazeneca. (...)
FDA kräver skärpt varningstext på TNF-blockerare
lakemedelsvarlden.se 5.9.2008
Det amerikanska Läkemedelsverket, FDA, gick på torsdagen ut med nya riktlinjer för fyra stycken läkemedel innehållande TNF-alfa-blockerare. Det är risken för allvarliga infektioner som nu måste finnas med i varningstext på produkterna.
Varning Produkterna det handlar om är Johnson & Johnson:s Remicade (infliximab), Wyeth:s Enbrel (etanercept), Abott:s Humira (adalimumab) och UCB:s Cimzia (cerolizumab). Alla fyra är så kallade TNF-alfa-blockerare som hämmar immunsystemet och används för behandling av bland annat reumatism, psoriasis och Crohn´s sjukdom. (...)
Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate
Ann Rheum Dis. 2008 Aug;67(8):1096-103. Epub 2007 Nov 29.
(...) CONCLUSIONS: In this study, abatacept and infliximab (3 mg/kg every 8 weeks) demonstrated similar efficacy. Overall, abatacept had a relatively more acceptable safety and tolerability profile, with fewer SAEs, serious infections, acute infusional events and discontinuations due to AEs than the infliximab group. Trial registration number: NCT00095147. (...)
Humira - ny sikkerhetsinformasjon
legemiddelverket.no 31.7.2008
Viktig informasjon til helsepersonell angående rapporter om hepatosplenisk T-cellelymfom (HSTCL) hos pasienter behandlet med Humira (adalimumab)
Legemiddelet Humira (adalimumab) er en TNF-alfa-hemmer godkjent til behandling av voksne pasienter med revmatoid artritt, psoriasisartritt, ankyloserende spondylitt, Crohns sykdom og psoriasis. Siden lanseringen i 2002, er det hos pasienter behandlet med Humira rapportert om tre tilfeller av hepatosplenisk T-cellelymfom (HSTCL). Dette er en sjelden form av non-Hodgkins lymfom med dårlig prognose. Produsenten Abbott sender nå ut brev med den nye informasjonen. Les den nye sikkerhetsinformasjonen her. (...)
Early Communication About an Ongoing Safety Review of
Tumor Necrosis Factor (TNF) Blockers
(marketed as Remicade, Enbrel, Humira, and Cimzia)
fda.gov 4.6.2008
FDA is investigating the possible association between the use of medicines known as tumor necrosis factor (TNF) blockers and the development of lymphoma and other cancers in children and young adults. These individuals were treated with TNF blockers for Juvenile Idiopathic Arthritis (JIA), Crohn’s disease or other diseases. JIA is the new name for what was called Juvenile Rheumatoid Arthritis (JRA). (...)
RA Drugs Linked to Slight Skin Cancer Risk
washingtonpost.com 29.8.2007
WEDNESDAY, Aug. 29 (HealthDay News) -- People taking rheumatoid arthritis drugs such as etanercept (Enbrel) or infliximab (Remicade) may be at a slightly increased risk for skin cancer, researchers report.
However, the risk is probably not significant enough to outweigh the benefits of these drugs, the researchers said.
These so-called biologic treatments work by blocking tumor necrosis factor alpha (TNF-alpha), which previous studies had found to be linked with increased risk of skin, lung and blood cancers.
"The risk of skin cancer is marginally increased among people with rheumatoid arthritis," said lead researcher Dr. Frederick Wolfe, a clinical professor of internal medicine at the University of Kansas School of Medicine. "But it's nothing that anybody should be worried about," he added. (...)
CORRECTED: Cancer risk from arthritis drugs overstated
reutershealth.com 11.8.2006
- Two biotech drugs used to treat rheumatoid arthritis -- Abbott Laboratories Inc.'s Humira and Johnson & Johnson's Remicade -- may raise the risk of cancer and infections but not as much as was feared, researchers said on Tuesday. (...)
Dr. Eric Matteson and colleagues at the Mayo Clinic in Rochester, Minnesota, who did the study published in May re-analyzed the data and added more data from other studies they had not considered before.
"We re-did the analysis completely," Matteson said in a telephone interview. The new analysis showed the cancer risk was 2.4 times greater among patients who used the drugs, and the risk of infectious disease was 1.8 times greater. (...)
Rheumatoid Arthritis Drug Linked to Cancers
ivanhoe.com 17.5.2006
-- A new analysis of previous studies shows rheumatoid arthritis drugs known as TNF- (tumor necrosis factor) blocking antibodies may increase the risk of cancer and infectious diseases.
"This study shows a strong association between treatment with TNF-blocking antibodies and the development of serious infections, such as pneumonia, and cancers," says Eric Matteson, M.D., from the Mayo Clinic in Rochester, Minn. "It's a very serious issue. TNF-blocking antibodies are effective for treatment for rheumatoid arthritis and related conditions, but patients and health care providers must know that there is an increased risk for these complications and be alert for them."
Investigators studied 3,493 patients who received TNF-blocking antibodies and 1,512 patients who received placebos. Researchers found those treated with TNF-blocking antibodies had about three-times the risk of developing cancer than those given a placebo and about two-times the risk of serious infection. Cancers were much more common in those patients treated with high doses of TNF-blocking antibodies. (...)
(Anm: Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275-85 (May 17).)
Rare Risks Tied to Anti-TNF Agents for RA
medpagetoday.com 16.5.2006
— Anti-tumor necrosis antibody factor therapy has been linked to a rare but increased risk of malignancy and serious infections in rheumatoid arthritis patients.
Seeking out the sparse harmful effects of anti-TNF antibody therapy, researchers at the Mayo Clinic here undertook a review and meta-analysis of nine "high-quality" controlled clinical trials, according to a report in the May 17 issue of the Journal of the American Medical Association.
Although meta-analysis is used as a powerful tool to assess drug efficacy, it is rarely used to assess harmful drug effects, wrote Tim Bongartz, M.D., of the Mayo Clinic, and colleagues.
The study database from EMBASE, MEDLINE, Cochrane Library, and electronic abstracts from major medical meetings, produced 3,493 RA patients treated with Remicade (infliximab) and Humira (adalimumab) for 12 weeks or more compared with 1,512 patients given a placebo.
Remicade is a partially humanized and Humira a fully humanized monoclonal antibody specific for TNF. The drugs neutralize both extracellular and membrane forms of TNF, a cytokine considered of major importance in the pathophysiology of rheumatoid arthritis, the researchers said.
The researchers used statistical methods designed for sparse data to calculate a pooled odds ratio (OR) for malignancies and for infections requiring antimicrobial therapy or hospitalization, or both, in the two groups of patients.
Effects for high and low drug doses were calculated separately, while published information was supplemented by direct contact with principal investigators and industry sponsors, Abbot and Centocor. The drug firms had no role in the study, the researchers said.
Combining the individual ORs of studies with at least one event in any group, the researchers found that the pooled OR for malignancy compared with placebo patients was 3.3 (95% confidence interval 1.2-9.1).
Malignancies were significantly more common in patients treated with higher doses compared with patients given lower doses of anti-TNF antibodies, the researchers said.
Subgroup analysis of malignancy in trials that used low- and high-dose treatment revealed a consistent and significant difference between the dose groups. (...)
(Anm: Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275-85 (May 17).)
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