Exploring New Osteoarthritis Treatment Options | ACR Convergence

Arthritis is one of the leading causes of limitations of daily activities, disability, and chronic pain in the US. Arthritis diagnoses are also associated with high rates of dispensed opioid prescriptions, potentially contributing to the substance use disorder public health crisis.¹

A number of new, nonopioid osteoarthritis treatment options are either available for patients or in the development pipeline.| Image Credit: crevis - stock.adobe.com

Osteoarthritis is the most common form of arthritis, affecting 32.5 million US adults. Pain from and/or hip osteoarthritis can affect sleep quality and mood and is associated with $17 billion in indirect and $65 billion in direct costs.²

Access to nonopioid pain management options for osteoarthritis are crucial. Research presented at ACR Convergence 2024 examined a number of potential treatments for osteoarthritis, along with patient outcomes and potential adverse effects.

Fasinumab

The newly developed anti-nerve growth factor monoclonal antibody fasinumab is being evaluated for its potential in alleviating osteoarthritis symptoms. However, some doses of this medication may be associated with increased adverse effects, including increased risk of adjudicated arthropathy and all-cause joint replacement.³

In a meta-analysis, researchers evaluated the safety and efficacy of fasinumab vs placebo therapy in osteoarthritis. Primary outcomes were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and function scores and Patient Global Assessment (PGA) scores.

A total of 6 randomized controlled trials of 9429 patients were included in the meta-analysis. Investigators found that at 16 weeks of treatment, doses of 1 mg subcutaneous fasinumab every 4 weeks, 1 mg subcutaneous fasinumab every 8 weeks, and 3 mg subcutaneous fasinumab every 4 weeks demonstrated a greater statistically significant reduction in WOMAC pain and function scores vs placebo. Notably, however, per minimal clinically important differences, only 1 mg and 3 mg every 4-week dosing may provide clinically meaningful reduction in WOMAC pain and function scores. The favored dosing regimen for increasing PGA scores at 16 weeks is 1 mg subcutaneous every 4 weeks.

RTX-GRT7039

Results of an early-phase clinical trial indicate that resiniferatoxin (RTX-GRT7039), a transient receptor potential vanilloid 1 (TRPV1) agonist, may provide meaningful and sustained analgesia for patients with knee osteoarthritis pain.4 TRPV1 has been identified as a critical driver of pain in osteoarthritis.

In a phase 2 study of 40 patients (25 women, mean age, 65.5 years), researchers evaluated the safety and efficacy of a single intra-articular injection of RTX-GRT7039. Patients were randomly assigned to receive either 2 mg or 4 mg RTX-GRT7039 (n=11 and 10, respectively) administered consecutively with intra-articular local anesthetic ropivacaine, or 4 mg or 8 mg RTX-GRT7039 or placebo, administered within 15 minutes following intra-articular ropivacaine. Primary endpoint for the study was VAS pain score on motion, and was documented at 3 and 6 months post-injection.

In all treatment groups, mean absolute VAS pain scores for pain on motion decreased rapidly from baseline; at months 3 and 6, mean percentage changes from baseline in VAS scores were higher in the RTX-GRT7039 group vs placebo. Analyses identified a higher percentage of participants with 50% or greater or 70% or greater reduction in VAS scores for pain on motion in all RTX-GRT7039 treatment groups vs placebo. Treatment groups also demonstrated a greater reduction in WOMAC total score, with consistent changes across WOMAC pain, function, and stiffness subscales.

Treatment emergent adverse events were comparable, and all were mild or moderate intensity. Two serious adverse events—lumbar spinal stenosis and knee arthroplasty—were reported in the 2 mg group, but neither were related to RTX-GRT7039 therapy.

READ MORE: Outcomes Vary When Using Cannabis for Pain Management in Rheumatic Disease

Analgesic Antidepressants

Patients using analgesic antidepressants—tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids—for osteoarthritis have worse pain severity and pain sensitization measures compared with those who use selective serotonin reuptake inhibitors (SSRIs), researchers found.⁴

Investigators evaluated data from 224 participants (mean age, 67.6 years; 75.5% women; mean BMI, 31.6) in the Multicenter Osteoarthritis (MOST) Study, a longitudinal cohort of older adults with, or at risk of, knee osteoarthritis who used either analgesic antidepressants or SSRIs to manage osteoarthritis pain.

There was no identified association between drug classes and either WOMAC pain or quantitative sensory testing measures. When evaluated longitudinally, patients taking analgesic antidepressants had marginally greater pain after 2 years compared with those taking SSRIs (β, 0.71; 95% CI, -0.02 to 1.44). Those taking analgesic antidepressants also had lower pressure pain threshold and were more likely to have insufficient conditioned pain modulation (β, 0.51; 95% CI, 0.05-0.97 and OR, 2.17; 95% CI, 1.08-4.37) vs SSRI patients.

“These results may suggest that managing depressive symptoms is important for pain management in [osteoarthritis],” the researchers concluded. “Our results highlight the important and complex interplay between depression, pain severity, and pain sensitization.”

In another study of analgesic antidepressants,⁵ researchers found that initiation of analgesic antidepressants was associated with a higher risk of knee or hip replacement vs the use of SSRIs.

In order to evaluate the relationship between these two classes of medications, researchers conducted a propensity score-matched, new-user design, active comparator, population-based cohort study using data from the IQVIA Medical Record Database from 2002 to 2021.

A total of 13,320 patients (mean age, 67 years; 63% women) initiated analgesic antidepressants and 13,320 patients (mean age, 67 years; 64% women), intiatiaed SSRIs. Within these groups, a total of 7.6% and 4.5%, respectively, had a knee or hip replacement with a median respective follow-up time of 8.6 and 8.1 years.

When adjusted for confounders and accounting for the competing risk of death, effect estimate hazard ratios were 1.61 and 1.67 for each group (95% CI, 1.46-1.78 and 1.51-1.85).

READ MORE: Nonopioid Options to Manage Chronic Pain in Veterans

Diclofenac Sodium 1% Gel

Diclofenac sodium 1% gel demonstrated significant improvements at 6 and 12 weeks of treatment in hand and knee osteoarthritis, according to researchers, based on mean scores of responses to individual physical function-specific questions on the WOMAC and Australian/Canadian Osteoarthritis Hand Index (AUSCAN).⁶

In a post-hoc analysis of two pooled, 12-week, randomized, double-blind, placebo-controlled trials of diclofenac sodium 1% gel vs vehicle, investigators found that treatment with diclofenac gel was associated with reductions in AUSCAN scores between 39% and 45% at week 6 and WOMAC scores between 46% and 60% at week 12. Statistically significant differences in favor of diclofenac gel were seen in all AUSCAN questions and in 14 of 17 WOMAC scores.

“The results highlight the effectiveness of these endpoints in evaluating the impact of treatment on daily activities relevant to [patients with osteoarthritis],” researchers concluded. “They may provide meaningful new ways for healthcare providers to communicate the benefits of using [diclofenac sodium 1% gel] as a treatment for both hand and knee [osteoarthritis].”

READ MORE: Nonopioid Pain Management Resource Center

References

1. Fallon EA, Boring MA, Foster AL, et al. Prevalence of diagnosed arthritis – United States, 2019-2021. MMWR Morb Mortal Wkly Rep. 2023;72(41):1101-1107. Doi:10.15585/mmwr.mm7241a1

2. OA prevalence and burden. Osteoarthritis Action Alliance. Accessed November 22, 2024. https://oaaction.unc.edu/oa-module/oa-prevalence-and-burden/

3. Khan MS, Moeen W, Banatwala UESS, et al. Certain dosages of fasinumab provides superior benefits over placebo in mitigating osteoarthritis symptoms albeit at increased health detriments: A systematic review and meta-analysis. Presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC. Abstract 1189.

4. Ostenfeld T, Ivanicius S, Stancik R, et al. An evaluation of the efficacy, pharmacokinetics and safety, of the transient receptor potential vanilloid 1 (TRPV1) agonist RTX-GRT7039 – a placebo-controlled study in patients with osteoarthritis knee pain. Presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC. Abstract 1211.

5. Wang Z, Mcginley B, LaValley M, et al. Relation of different types of antidepressants use to pain severity and measures of pain sensitization in knee osteoarthritis. Presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC. Abstract 1196.

6. Wang Z, Westerland M, Peloquin C, et al. The relations of analgesic antidepressants use to knee or hip replacement among osteoarthritis patients compared to selective serotonin reuptake inhibitors in a large prospective cohort. Presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC. Abstract 1195.

7. Nicholson K, Sanchez E, Maybaum N, Petruschke R. Diclofenac sodium 1% gel improves physical function in the performance of important activities of daily living in patients with hand or knee osteoarthritis. Presented at: ACR Convergence 2024; November 14-19, 2024; Washington, DC. Abstract 1199.