Anti-NGF Pain Drugs in People: What Side Effects Were Seen?

Scientists have been studying a new type of pain medicine called anti-NGF monoclonal antibodies. These drugs were made to help people with long-lasting pain, especially from arthritis.

NGF stands for nerve growth factor. It is a natural chemical in the body that helps pain signals travel from injured joints to the brain. Anti-NGF drugs work by blocking NGF, which can lower pain.

Some of the best-known anti-NGF drugs studied in people include tanezumab, fasinumab, and fulranumab.

Even though these drugs helped reduce pain, researchers found important side effects that limited their use.

How often did side effects happen?

In large clinical studies, people taking anti-NGF drugs had side effects more often than people taking a placebo (a fake treatment) or other pain medicines.

A large review of many studies found that about 10–15% more people had at least one side effect when taking anti-NGF drugs compared to people who did not take them.
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00817/full

Most side effects were mild to moderate, but some were serious and affected the joints.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9047886/

Common, mild side effects

The most common side effects were not life-threatening and often went away after treatment stopped. These included:

• Swelling in the legs or feet
• Joint or limb pain
• Tingling, numbness, or “pins and needles” feelings in the hands or feet
• Changes in skin sensation

In many studies, nerve-related symptoms like tingling or numbness happened in fewer than 10% of patients.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9047886/

Serious joint problems

The most important safety concern with anti-NGF drugs involved the joints.

Some patients developed very fast joint damage called rapidly progressive osteoarthritis (RPOA). This means the joint wore down much faster than expected.

Doctors also reported:

• Severe joint damage
• Bone fractures near joints
• Bone death (osteonecrosis)
• Need for total joint replacement surgery

In studies of tanezumab for arthritis pain, about 1–2% of patients developed these serious joint problems. These events were more common at higher doses and when anti-NGF drugs were used together with NSAIDs like ibuprofen or naproxen.
https://www.fiercebiotech.com/biotech/pfizer-lilly-ngf-pain-drug-wins-again-but-safety-concern-won-t-go-away

People taking placebo usually had little to no risk of these joint problems.

Because of these findings, the U.S. FDA placed a temporary hold on these drugs in 2010 while safety was reviewed.
https://www.medcentral.com/meds/nerve-growth-factor

What about other serious side effects?

Outside of joint damage, serious side effects like heart, kidney, or life-threatening events were usually similar between anti-NGF drugs and placebo or NSAIDs.

Some people stopped treatment early because of side effects, but this was not very different from people stopping NSAIDs due to stomach, kidney, or heart problems.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9047886/

An example from a large study

In a phase III study of tanezumab for cancer-related pain:

About 74% of people taking tanezumab had at least one side effect.
About 69% of people taking placebo had at least one side effect.

Joint-related serious side effects only occurred in the tanezumab group.
https://pubmed.ncbi.nlm.nih.gov/37343145/

Why these drugs were not approved

Anti-NGF drugs clearly reduced pain for many people. However, the risk of sudden and severe joint damage was considered too serious.

Later studies tried lower doses and closer joint monitoring, but safety concerns remained. Because of this, anti-NGF monoclonal antibodies were not approved for routine use in people.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8253925/

Take-home message

Anti-NGF pain drugs showed strong pain-relief benefits, but they also caused unique joint-related risks not seen with many other pain medicines. Most side effects were mild, but a small number of patients developed serious and permanent joint damage. These safety concerns ultimately limited their use in human medicine.