Pilot Study of Low-dose Naltrexone for the Treatment of Chronic Pain Due to Arthritis: A Randomized, Double-blind, Placebo-controlled, Crossover Clinical Trial.

PURPOSE: Low-dose naltrexone (LDN) is commonly used to control pain and other symptoms, especially in patients with autoimmune diseases, but with limited evidence. This study tests the efficacy of LDN in reducing chronic pain in patients with osteoarthritis (OA) and inflammatory arthritis (IA), where existing approaches often fail to adequately control pain. METHODS: In this randomized, double-blind, placebo-controlled, crossover clinical trial, each patient received 4.5 mg LDN for 8 weeks and placebo for 8 weeks. Outcome measures were patient reported, using validated questionnaires. The primary outcome was differences in pain interference during the LDN and placebo periods, using the Brief Pain Inventory (scale, 0-70). Secondary outcomes included changes in mean pain severity, fatigue, depression, and multiple domains of health-related quality of life. The painDETECT questionnaire classified pain as nociceptive, neuropathic, or mixed. Data were analyzed using mixed-effects models. FINDINGS: Seventeen patients with OA and 6 with IA completed the pilot study. Most patients described their pain as nociceptive (n = 9) or mixed (n = 8) rather than neuropathic (n = 3). There was no difference in change in pain interference after treatment with LDN (mean [SD], -23 [19.4]) versus placebo (mean [SD], -22 [19.2]; P = 0.90). No significant differences were seen in pain severity, fatigue, depression, or health-related quality of life. IMPLICATIONS: In this small pilot study, findings do not support LDN being efficacious in reducing nociceptive pain due to arthritis. Too few patients were enrolled to rule out modest benefit or to assess inflammatory or neuropathic pain. CLINICALTRIALS: gov identifier: NCT03008590.

Stiff-person syndrome: persistent elevation of glutamic acid decarboxylase antibodies despite successful treatment with rituximab.

Stiff-person syndrome is a rare neurologic disorder characterized by fluctuating and progressive stiffness of axial and limb musculature. The high prevalence of autoantibodies and associated autoimmune diseases in patients with stiff person syndrome suggests that it may have an autoimmune etiology. We report a case of a 62-year-old man with diabetes who developed progressive stiffness of the hips and legs and elevated levels of antibody to glutamic acid decarboxylase. He had a partial response to both baclofen and diazepam, but could not tolerate the treatment because of somnolence. He eventually received 2 infusions of rituximab 1000 mg a week apart. The baclofen was discontinued and the diazepam was tapered. However, 6 months after the rituximab treatment, despite continued clinical improvement the patient had persistently elevated titers of antibody to glutamic acid decarboxylase. We postulate that rituximab was associated with clinical improvement through mechanisms other than antibody depletion.