Potential OA Treatment - Chemokine CCL17 Inhibition Save

Patients with osteoarthritis (OA) of the knee receiving an investigational chemokine inhibitor showed some improvements in pain and disability, said researchers with the drug's developer.

In a phase I study that also included placebo-controlled efficacy testing, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for both knee pain and function were significantly lowered after 8 weeks among those assigned to the active agent relative to placebo, according to Riju Ray, MD, PhD, of GSK in Research Triangle Park, North Carolina, and colleagues.

No problems with safety or tolerability were identified, the group reported in Annals of the Rheumatic Diseases, leading them to conclude that "[t]hese promising data warrant further study of the efficacy and safety of GSK3858279 for treating chronic pain in adults with OA."

No disease-modifying therapy exists for OA -- only palliatives such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids that relieve pain but don't halt the joint deterioration. Positive results have been obtained from certain products used in rheumatic joint diseases in some initial studies, yet failures have been more numerous. OA's etiology, of course, differs markedly from autoimmune joint disorders, but inflammation is very often present and some immune dysregulation is clearly involved.

The GSK researchers noted that chemokines -- signalling molecules that serve to attract immune cells to infection and injury sites, and whose receptors are a target for the HIV drug maraviroc (Selzentry) -- are known to play a role in pain transmission. With support from animal models, they believed a drug to inhibit chemokine action would be worth exploring in OA. The company has developed GSK3858279, a monoclonal antibody targeting a chemokine molecule called CCL17 that has appeared to be particularly important in pain signalling. Indeed, another phase I clinical study with this agent reported last month showed some beneficial effects in a variety of pain states.

For the OA trial, Ray and colleagues first recruited 49 healthy individuals for the standard safety, tolerability, and pharmacokinetic analysis standard for a phase I study. More unusually, this was followed by a placebo-controlled phase with 48 knee OA patients who were treated with either GSK3858279 or placebo for 8 weeks, each given weekly by subcutaneous injection.

In the second part, median patient age was 59 and just over half were men. Most were overweight, with a median body mass index of 29.2. Median patient self-ratings of average knee pain and worst pain were 5.3 and 6.1, respectively, on a 10-point scale. Median WOMAC scores at baseline were 5.4 for pain and 5.4 for function.

After 8 weeks, improvements were seen in both the active-treatment and control groups, but they were greater in the former, with median differences as follows:

• Self-rated average pain: -1.18 (95% credible interval [CrI] -2.15 to -0.20)
• Worst pain: -1.09 (95% CrI -2.29 to 0.12)
• WOMAC pain: -1.41 (95% CrI -2.35 to -0.46)
• WOMAC function: -1.29 (95% CrI -2.28 to -0.29)

In most of the active-treatment group, improvements were "clinically meaningful," the researchers indicated.

WOMAC stiffness scores were assessed as well; these also showed a trend favoring the drug but it failed to reach significance.

Across both parts of the study, adverse events were common with the GSK agent and placebo, with no notable difference between them. Events were mostly mild. The most common were nasopharyngitis, headache, and contact dermatitis.

"Future studies will expand on these findings by enrolling a more diverse population, extending the GSK3858279 treatment duration, and evaluating different dose regimens," Ray and colleagues promised.