It is indeed tempting to compare IVD degeneration to OA because the profile of cytokine production in human IVDs looks like the one observed in OA and because resident cells from discs behave like chondrocyte cells. Some evidence suggests that IL-1β is not only involved in the structural damage process of OA but also plays an important role in pain transmission. Results from in vitro studies and animal models of OA support the dominant role of IL-1β early in the disease process. Moreover, intra-articular delivery of anakinra (recombinant methionyl human receptor antagonist (r-met HuIL-1ra)) may have beneficial effects on symptoms and structural modifications in animal models of OA [5–7]. Treated animals in these studies showed less severe cartilage lesions, less synovitis, significant reduction in the size of osteophytes, and significant improvement in clinical indicators of pain and disease activity.
A first randomized controlled trial in patients with knee OA demonstrated a good safety profile for one intra-articular injection of IL-1ra (150 mg, the maximum tolerated dose) [8]. We performed a multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical response, safety, and tolerability of a single intra-articular injection of anakinra (50 or 150 mg) in 170 patients with symptomatic OA of the knee [9]. There was no improvement in knee pain, function, or measures of cartilage turnover with anakinra treatment compared to placebo at the main endpoint (month 1). A tendency for improvement was noticed in the 150 mg group at day 4 (in keeping with the short half-life of IL-1ra), suggesting that IL-1 inhibition may be therapeutically relevant.
In the context of LBP, the use of IL-1 blockers is very attractive, although many questions need to be addressed before starting to use such therapy: what is the best route of administration, how many injections should be given, what types of IL-1 blockers should be used, and at what stage of the disease should therapy be given?