Anti-Nerve Growth Factor Antibodies Reduce OA Pain, Association With Long-Term Adverse Events Remain

Although anti-nerve growth factor (NGF) antibody therapy can reduce pain and improve function in symptomatic knee and/or hip osteoarthritis, these treatments are associated with therapy discontinuation over time due to adverse events (AEs), according to research published in Pain Medicine.

Through a systematic review, researchers aimed to synthesize the currently available literature on anti-NGF antibodies in osteoarthritis pain and further determine whether these antibodies are associated with more change in Western Ontario and McMaster Universities (WOMAC) scores for pain and physical function, patient global assessment scores, and AE incidence. Thirteen studies were included in the review, for a patient cohort of 8145 study participants diagnosed with hip and/or knee osteoarthritis.

WOMAC pain, physical function, and stiffness scores were evaluated using 6, 7, and 5 studies (n=2016, n=2251, and n=1640, respectively) with 23, 21, and 17 pairwise comparison groups. For each measure, a significant difference between the treatment and placebo groups was noted (standardized mean difference [SMD], -0.50, -0.82, and -0.88; 95% CI, -0.71 to -0.28, -1.09 to -0.55, and -1.22 to -0.54; I²=88%, 94%, and 95%, respectively; P <.00001 for all).

Five studies with 1509 participants in 19 pairwise comparison groups were used to determine the effect of anti-nerve growth factor agents on patient global assessment score. Investigators found no statistically significant difference in mean patient global assessment score change between treatment and placebo groups (SMD, -0.14; 95% CI, -0.42 to 0.09; Z=1.24; P =.22). When subset analysis was performed, however, the improvement was significant only in patients treated with fulranumab compared with those treated with tanezumab.

All studies reported AEs. The most common included arthralgia, hypoesthesia, paraesthesia, and peripheral edema. A total of 148 cases of treatment discontinuation due to serious AEs were reported from a total of 2422 participants who received treatment. AE and serious AE incidences were higher in patients who received higher doses of the study drugs.

In total, 9 studies reported treatment discontinuation due to adverse events. Treatment was associated with a significant increase in therapy discontinuation resulting from AEs compared with placebo (relative risk, 2.11; 95% CI, 1.57-2.84; P <.0001; I²=0%).

Study limitations include the potential risk of publication bias, the use of only a small number of studies for some scoring systems, an inability to further stratify the effect that body mass index or comorbidity might have on the analysis, and limited follow-up of included participants.

“Our meta-analysis demonstrates that anti-[nerve growth factor] antibody treatment alleviates pain and improves function in patients with symptomatic [osteoarthritis],” the researchers concluded. “Further clinical randomized controlled trials are needed to characterize the efficacy and safety of these agents for the management of [osteoarthritis] pain.”

Reference

Seah KTM, Rammanohar J, Sutton J, To K, Khan WS. The effectiveness of anti-nerve growth factor monoclonal antibodies in the management of pain in osteoarthritis of the hip and knee: a PRISMA systematic review and meta-analysis. Pain Med. Published online February 22, 2021. doi:10.1093/pm/pnaa441