Clinical Trials

Concurrent Session 11

Date/Time: Sunday, May 3, 2020 - 8:45 AM to 10:15 AM
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Description:

Biological Agents in OA - Hopes and Disappointments

The use of biologics in a chronic disease such osteoarthritis has raised a lot of hopes.

This presentation will focus on the more recent data of biologics in OA.

Biologics can be classified in 3 subgroups. The one which targets pain and only pain. The one which targets the destruction of the cartilage and finally the third one which targets the stimulation of cartilage repair. The two latest could be considered as DMARDs with or without a symptomatic effect.

News biologics agents against pain in OA are centered on anti NGF strategy. While the analgesic effect was dramatic using high dose and intravenous route of administration, emerging severe arthropathies have dampen down this enthusiasm. Anti-NGF is nowadays used by subcutaneous injections. The effect on pain is still superior to placebo but less important. The safety profile is reassuring, though warning is still required when drugs will be distributed on a large open market.

Biologics agents against main cytokines in OA (IL1, TNFa, IL6) have been tested in knee and in hand OA. The results are really disappointing and this review will try to answer to the question. Why such a failure of biologics in OA? News biologics targeting WNT, bradykinin are under development but so far, the preliminary results needs to be confirmed in larger trials in humans.

Finally, after several pilot studies with different growth factors and mitigated results, the real hope has emerged with the use of intra-articular administration of FGF-18, every 6 or every 12 months, during 2 years. We have now encouraging results at year 2 with high dose of FGF-18 in terms of structural evolution evaluated by MRI.

If results of this long term trial (FORWARD) (5 years) are confirmed in others trials, FGF-18 may constitute the first real DMARDs in OA.

HOT-SHOTS

  • Biologics in osteoarthritis may target pain, structural evolution or both.
  • The use of anti NGF biotherapy demonstrated significant reduction of pain without structural effect. After worrying of severe articular side effects with high dose and i.v administration, the latest studies are more reassuring, using subcutaneous injections and lower doses. Nevertheless, caution is still required when large diffuse administration will occur.
  • Strategy using anti IL1, anti TNFa have failed both on the evolution of pain and on the structural evolution in knee OA and in hand OA.
  • It is time rethink the opportunity of such strategy and to look for news targets such as WNT and chemokines.
  • FGF-18,an anabolic growth factor, ¬†administered by intra articular injections with long interval, has demonstrated a DMARD effect in knee OA. However others trials are necessary to confirm with very encouraging results.

Speaker(s):