Decimation of the Indian vulture population in the 1990’s triggered an ecological catastrophe - Read

Cyclo-oxygenase inhibitors: A review of anti-inflammatory effects and side-effects - Read

Six weeks of low-dose prednisolone was safe and effective for people with a painful flare of hand osteoarthritis - Read

A 2021 review article about the selective EP4 antagonist Galliprant - Read

Antarctic krill fisheries may be harming penguins - Read

Rats with surgically damaged knee cartilage suffered accelerated arthritis after receiving an anti-NGF antibody - Read

The authors of a 2018 review article seemed unconcerned about the severe side-effects of anti-NGF drugs reported in humans - Read [Competing interest statement on page 11]

COAST is a set of guidelines about how to treat canine arthritis. While six out of nine experts recommended Librela as a suitable initial treatment for dogs with mild osteoarthritis [page 10], it's important to note that six experts received payments from Zoetis, the manufacturer of Librela [page 22] - Read

Dr George Yancopoulos, Chief Scientific Officer at Regeneron Pharmaceuticals, discusses the neurotrophin family's complex connection to serious side-effects - Read [pages 299-301]

In 2015, the anti-NGF drug market was forecast to achieve $11 billion sales by 2023 - Read [page 298]

Dr. Marek Honczarenko, a senior executive at GlaxoSmithKline, proposed studying genetic variations related to nerve growth factor (NGF) to predict side-effects of anti-NGF drugs - Read [page 187]

Researchers identified a link between maintenance methadone doses and NGF genotype in recovering heroin addicts - Read

New NGF analogues have the potential to balance the benefits and drawbacks of anti-NGF antibodies - Read

Three pharmaceutical companies stopped developing anti-NGF drugs in the same class as Librela. Johnson & Johnson dropped fulranumab in 2016 - Read - Pfizer dropped tanezumab in 2021 - Read - and Regeneron dropped fasinumab in 2022 - Read

The science behind the Covid-19 vaccines - Read

A 2013 UK survey found cancer (16.5%) and musculoskeletal disorders (11.3%) were the leading causes of death in pet dogs - Read

Elbow arthritis was cited as a factor in euthanising 4/10 dogs with elbow dysplasia - Read

The South African government's decision to promote natural alternatives over prescription drugs for AIDS is estimated to have led to 343,000 preventable deaths - Read

Dr Ben Goldacre, a physician, academic, activist, and author, is famous for his work on the application and misuse of science. In this excerpt from his book, Bad Science, Dr Goldacre tells the controversial story of Matthias Rath, a German doctor and vitamin salesman, and his involvement in the AIDS epidemic - Read

Fifty-eight caregivers of dogs with painful arthritis were randomly assigned to receive either a potent painkiller (deracoxib) or a placebo. Neither the caregivers nor their veterinarians knew which treatment was being administered. To assess the placebo effect, caregiver and veterinary evaluations were compared to objective gait analysis. The results were sobering: In 57% of cases, caregivers reported improvement or no change even though their dog's lameness had either remained the same or worsened based on objective data - Read

University of Minnesota researchers concluded that Dasuquin, a popular supplement for arthritic dogs, did not alleviate pain, reduce treatment failures, or improve activity levels compared to an inactive placebo - Read

A 2022 systematic review found limited benefits for collagen and no benefit of chondroitin-glucosamine supplements for painful arthritic dogs - Read

Dr Stephen Novella, a clinical neurologist at Yale, promotes critical thinking and evidence-based medicine. In this article, he provides evidence-based insights into the supplement industry - Read

Zoetis reported a 0.18% adverse event rate for Librela in an email to the global financial media group, Investopedia - Read - A team of mathematicians question Zoetis’ estimate - Read

Two weeks of carprofen (Rimadyl, Zoetis) resulted in clinical improvement in 62% of dogs, with a 3.8% adverse event rate. After two months of treatment, 91% of dogs were improved, and the adverse event rate dropped to 3.6% - Read

Of the 805 dogs enrolled in a long-term carprofen trial, 12% discontinued treatment due to limited improvement, and 3% discontinued treatment due to side-effects. The most common side-effects were vomiting and/or diarrhoea (2.7%), and/or reduced appetite (0.9%). Three-quarters of side-effects occurred within the first 3-weeks of treatment. Two dogs (0.3%) developed liver toxicity; one required intensive treatment but both recovered - Read

According to the Veterinary Medicines Directorate (VMD), carprofen was associated with liver toxicity and mortality in approximately 1 in 20,000 doses - Read

Carprofen reduced the structural damage and abnormal bone metabolism associated with experimental osteoarthritis - Read

Dr. Sheldon Sommers, a pre-eminent professor of clinical pathology, asserted that a statistical correlation between smoking and lung cancer did not prove causation. His core argument was that not all smokers develop lung cancer, and not all lung cancer patients are smokers - Read

Anti-NGF drugs produced better short-term pain relief compared to NSAIDs in arthritic people enrolled in six randomized controlled trials. However, severe adverse events were 30% more likely with anti-NGF drugs, and 0.7-6.3% of patients suffered accelerated arthritis progression. Twice as many patients treated with anti-NGF drugs needed a joint replacement - Read

Stanley, a 2-year-old Labrador treated with 6-doses of Librela, developed rapidly progressive elbow osteoarthritis and a pathological humeral fracture. His report was submitted via Zoetis to the VMD (reference GBR-ZOETISPV-2024-UK-00209). Tragically, Stanley did not recover and was euthanised on 3rd April 2023. Zoetis acknowledged this outcome on 4th June 2024 - Read

A June 4, 2024 search of EudraVigilance for Librela-related musculoskeletal disorders found 29 reports of fractures - Read

An expert panel overwhelmingly rejected tanezumab, Librela's human equivalent, with a 19-to-1 vote. Several experts described tanezumab's average benefit as 'modest' - Read

On 20th November 2023, the Center of Veterinary Medicine (CVM) of the U.S. Food and Drug Administration (FDA) cited Zoetis for making "false or misleading claims and representations about the efficacy of Librela" on their website. The FDA's letter is available here, and the revised page can be found here

A University of Rochester professor suggested halting treatment for patients who didn't show significant improvement after one injection of an anti-NGF drug - Read [page 377]

A study of 3021 osteoarthritis patients found that tanezumab, the human equivalent of Librela, improved hip and knee pain significantly more than NSAIDs, but only in the first 4-months of treatment - Read

A course of three epidural injections resulted in sustained improvement for 8/10 dogs, with 5/10 achieving a full recovery - Read

Day 28 was the pre-specified primary effectiveness end point for Librela’s two field trials. The European study met statistical significance (28% difference versus a saline injection) but the U.S. study did not (12% difference) - Read

Oxycontin is a powerful painkiller but suffers the serious limitation of addiction. It’s manufacturer, Purdue Pharma reaped $31 billion dollars from Oxycontin based on misinterpretation of published data - Read

The first human clinical trial of an anti-NGF painkiller was published in 2010 - Read

Accelerated arthritis must be studied radiographically. Only 1-in-3 human patients with rapidly progressive osteoarthritis (RPOA) caused by the human equivalent of Librela showed pain or swelling - Read [page 171]

Risk of accelerated arthritis increased with higher doses and when the anti-NGF drug was combined with NSAIDs - Read [page 57]

The FDA rejected a biological license application for tanezumab, the human equivalent of Librela, after reviewing data from 41 studies conducted over 15 years, involving 17,000 patients. A team of 250 independent experts read 50,000 x-rays - Read - In Zoetis' field trials, only 276 dogs received Librela, and follow-up x-rays were not performed to check for accelerated arthritis.

A review article describing the risk evaluation and mitigation strategy employed in human clinical trials - Read

Among the 3031 patients enrolled in post-2015 trials using a risk evaluation and mitigation strategy (REMS), 3.2% who received tanezumab without concurrent NSAIDs suffered adverse joint events - Read

A three-year clinical hold on human anti-NGF drug trials was triggered by research showing a reduction in nerve cell count in adult mice, which was thought to be caused by cell death - Read - These findings were not replicated in monkeys, and the FDA hold was lifted in 2015 - Read

Knee meniscal injury has been proposed as a predisposition for rapidly progressive osteoarthritis (RPOA) in humans - Read

There was no correlation between pain relief and serious adverse joint events for Librela's human equivalent, tanezumab - Read

Dr Maria Suarez-Almazor, chairperson of the FDA panel which rejected a biological license application for tanezumab (Librela’s human equivalent) said, “it is counter-intuitive to use a drug for osteoarthritis that actually makes osteoarthritis worse.” - Read [page 142]

Zoetis assert that dogs don't suffer the accelerated joint damage seen in humans and lab animals treated with anti-NGF drugs. Their claim is based on data collected from eight healthy young beagles - Read

Zoetis declined an invitation to provide annotated images and explain why they described cartilage erosion in two healthy young beagles treated with Librela as mild pathology - Read

Rabbits treated with anti-NGF monoclonal antibodies developed severe joint degeneration - Read

Thousands of musculoskeletal side-effects were reported by caregivers of dogs receiving Librela - Read - yet Zoetis claimed their database contained not a single report of joint-related adverse events - Read

Eight healthy beagles were successfully treated with Librela and the NSAID carprofen for two weeks without adverse reactions - Read - In human trials, concurrent use of NSAIDs for less than 10-days within each 2-month cycle of anti-NGF drug dosing was safe. However, prolonged combined use was associated with a significantly increased risk of accelerated joint degeneration - Read [page 229]

It is estimated that over 10,000 children suffered birth defects caused by their mothers taking thalidomide during pregnancy - Read

Merck voluntarily withdrew their painkiller rofecoxib (Vioxx) after clinical trials revealed a significantly increased risk of heart attack and stroke in patients taking it for at least 18 months - Read

Fen-phen combined the weight loss drugs fenfluramine and phentermine. It was very effective for short-term weight loss, but caused serious heart valve problems and pulmonary hypertension - Read