Access to the PPM Journal and newsletters is FREE for clinicians.
19 Articles in Volume 19, Issue #6
Arthrofibrosis: Targeting Hormones after Childbirth to Relieve Frozen Shoulder, Inflamed Joints
Can CGRP Help Clarify Why Migraine Is More Common in Women?
Case Report: Managing Chronic Pelvic Pain in Men
CGRP Monoclonal Antibodies for Chronic Migraine: Year 1 of Clinical Use
Chronic Pelvic Pain as a Form of Complex Regional Pain Syndrome
Correspondence: Continuing the “Pain Specialist” Dialogue
Endometriosis and its Misunderstood Etiology
Evolving Management Strategies for Osteoarthritic Pain
Gamma PEMF Therapy: A Pilot Study For Its Use in Managing Opioid Addiction
Guest Editorial: Sex Differences in Pain
How to Provide Effective Pain Management to LGBTQ Individuals
Interscalene Peripheral Nerve Stimulation for Post-Operative Chronic Shoulder Pain
New ICD-11 Codes Set to Improve Pain Care in the Primary Setting
Perspective: Could NGF Antagonists Be the Safest, Most Efficacious Class of Drug We Have to Treat Pain?
Rheumatoid Arthritis and Cognition: Is There a Genetic Link?
Targeting Nerves Provides Alternative to Opioids for Joint Arthroplasty
The Sex Question in Primary and Pain Care
What is capsaicin’s role in treating osteoarthritis?
When Pain Clinicians Have to Be the Villain: Communication Strategies to Bridge the Divide

Perspective: Could NGF Antagonists Be the Safest, Most Efficacious Class of Drug We Have to Treat Pain?

A reader offers another opinion in the discussion around the potential of NGF antagonists.
Pages 36-37

I would like to commend Drs. Ramos and Oltman for their recent overview of the nerve growth factor class of drug in this journal, which included a discussion and rating by Editors-at-Large Jeff Gudin, MD, and Jeffrey Fudin, PharmD.1 It was an excellent review but I vehemently disagree with the 3.5-star rating out of 5 for this class (see here).

I am the chief medical physician at the Arizona Research Center and a board-certified orthopedic surgeon. Founded in 1997, this center has participated in an estimated 1,000 clinical trials and our team, including Louise Taber, MD, have authored close to 100 articles, a large percentage of which have related to narcotic and non-narcotic pain medications, in peer-reviewed clinical journals.

My experience with anti-nerve growth factor (NGF) drugs started with Rinat Neuroscience Corporation clinical trials. Pfizer purchased Rinat in 2006. Our research center has since participated in almost every Pfizer, Regeneron, and Janssen NGF trial for patients who have osteoarthritis of the hip, knee, and spine with at least moderate pain.

In 2010, the FDA put on hold all anti-NGF trials because of the concern that this class of drug caused rapidly progressive osteoarthritis (RPOA). The incidence at that time of RPOA in the Pfizer trials was about 2% (the range has since been between 2 and 6%).

Anti-NGF drugs may be too good, claims the author, noting that when patients feel their pain has been eliminated, they may become more active and thus inadvertently re-injure themselves or cause a flare-up. (Image: 123RF)

At the time these trials were put on hold, I received more than 100 letters from patients around the country. Every patient essentially wrote the same thing: “This drug made my life. Now stopping this drug has ruined my life.” I, in turn, sent copies of these letters (I still have the originals) to Pfizer and the FDA but never heard a response.

The main problem with this class of drug, in my view, is that anti-NGF drugs are too good. Pain is protective and by eliminating pain, which is a common result with this class of drug, patients return to activities they have not participated in for years. Some patients, despite being cautioned, are hiking and running, which, in patients with KL3 to KL4 x-ray joint findings, is unwise and may lead to increased joint problems.

I have met with physicians working at companies developing these products and have had the opportunity to participate on advisory panels. The following are several questions that I have asked but never received a response:

  • What is the incidence of x-ray progression of osteoarthritis from KL3 to KL4 in the general population? How does this differ from patients on the study drug?
  • Is there data from clinical trials related to increased activity comparing patients on placebo versus study drug? Similarly, is there data comparing the reduction of pain in patients on the study drug and increased activity?
  • Is there any information relating to increased activity leading to RPOA?
  • How many deaths, if any, have occurred on the study drug compared to narcotics or biologics during the same time period?
  • What percentage of patients on the study drug progressed to total joint replacement compared to the general population?

I realize that the data, when a study drug is compared to a placebo, show an increased incidence of RPOA. However, I question: How much of this is truly related to the study drug versus being related to the patient’s increased activity? It is obvious that patients on the study drug are more active compared to those on placebo. Why has this never been taken into consideration when discussing increased joint findings?

My clinical experience with the anti-NGF class is that there is nothing better or safer to treat pain. Pharma may be concerned that, if this drug is approved, then there may be a requirement that patients need an MRI prior to taking the medication. This would represent a death note for this drug.

I feel strongly that the safety of this class of drugs should be a 4.9 out of 5.0 (Editor’s Note: Drs. Gudin and Fudin’s 3.5 out of 5.0 review was based on novelty, risk-benefit ratio, clinical utility, scientific rigor of studies, and market potential). I have never been involved with a drug where I have received so many hugs from patients as a result of the reduction in their pain. In my view, this class of drug is a game-changer and I feel it may be criminal not to see this class approved.

To conclude, I am not aware of any reported deaths since 2006 related to anti-NGF medications. Yet how many tens of thousands of patients have died from biologics and/or narcotics in the same time period? There is a concern that 6% of anti-NGF patients experience rapid progression of their osteoarthritis. However, as noted, there are no data available to prove this change is the result of study drug itself or of increased activity due to the patient’s pain reduction. How many of these patients would have normally progressed to end-stage disease? With the emphasis today on narcotic abuse and related deaths, it is difficult to understand how this class of drug could not be approved.


*Dr. Gimbel discloses that he has been on Pfizer tanezumab advisory panels and, as stated in the text, has been involved in clinical trials for the anti-NGF drugs mentioned herein. 

Last updated on: November 13, 2019
Continue Reading:
Analgesics of the Future: Inside the Potential of Nerve Growth Factor Antagonists
close X