Fluge Øystein, Rekeland Ingrid Gurvin, Sørland Kari, Alme Kine, Risa Kristin, Bruland Ove, Tronstad Karl Johan, Mella Olav
The Cancer Clinic, Haukeland University Hospital, Bergen, Norway.
Institute of Clinical Sciences, University of Bergen, Bergen, Norway.
Front Med (Lausanne). 2025 Jul 9;12:1607353. doi: 10.3389/fmed.2025.1607353. eCollection 2025.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on patients' symptoms.
To evaluate feasibility and toxicity of plasma-cell targeting treatment using the subcutaneous anti-CD38 antibody daratumumab (Darzalex) in moderate to severe ME/CFS, and to assess the clinical course through 12-24 months follow-up after daratumumab intervention.
We performed a prospective, open-label pilot trial (EudraCT 2022-000281-18). Ten female patients were enrolled. Following 12 weeks run-in, six patients received four daratumumab injections. The next four patients received four, followed by three additional injections from week 14.
All planned treatments were administered, and there were no serious adverse events. Four patients had no significant clinical changes. Six patients experienced marked improvement. For all 10 patients, mean SF-36 Physical Function (SF-36 PF) increased from 25.9 to 55.0 at 8-9 months ( = 0.002). DePaul Questionnaire-Short Form (DSQ-SF) symptom scores decreased from 72.3 to 43.1 ( = 0.002). In six responders, mean SF-36 PF increased from 32.2 to 78.3, and DSQ-SF score decreased from 71.1 to 24.3. Five of these six patients had major and sustained improvement with a mean SF-36 PF of 88 (range 80-95) toward end of follow-up. Mean steps per 24 h was 3,359 (range 1,493-6,277) at baseline. At 8-9 months, the mean number of steps was 5,862, and 7,392 in the six responders. All five patients with sustained improvement reached a mean step count above 10,000/24 h for some weeks, and above 15,000 on individual days. Relative reduction of serum IgG levels was 54% in six patients with clinical improvement, and 40% among four with no benefit. Low baseline NK-cell count in blood was significantly associated with lack of clinical response.
Subcutaneous daratumumab in 10 ME/CFS patients was well tolerated. In six patients, treatment was associated with clinical improvement and concurrent transient reduction of serum IgG levels, indicating important pathomechanistic roles for long-lived plasma cells and functional autoantibodies. No definite conclusions should be drawn before a randomized study has been performed.
https://euclinicaltrials.eu, Identifier: 2022-000281-18.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）给患者带来了较低的生活质量，并造成了巨大的社会成本。迫切需要阐明疾病机制并进行合理治疗。我们的工作假设是，一部分患者的ME/CFS与感染后出现的功能性自身抗体有关，并且浆细胞耗竭导致血清免疫球蛋白短暂减少将对患者症状产生有益影响。
评估皮下注射抗CD38抗体达雷妥尤单抗（兆珂）治疗中度至重度ME/CFS的可行性和毒性，并在达雷妥尤单抗干预后通过12 - 24个月的随访评估临床病程。
我们进行了一项前瞻性、开放标签的试点试验（欧盟临床试验注册号：2022 - 000281 - 18）。招募了10名女性患者。在12周的导入期后，6名患者接受了4次达雷妥尤单抗注射。接下来的4名患者先接受4次注射，然后从第14周开始再额外接受3次注射。
所有计划的治疗均已实施，且未发生严重不良事件。4名患者无明显临床变化。6名患者有显著改善。对于所有10名患者，8 - 9个月时，简明健康调查量表（SF - 36）身体功能（SF - 36 PF）评分从25.9提高到55.0（P = 0.002）。德保罗简短问卷（DSQ - SF）症状评分从72.3降至43.1（P = 0.002）。在6名有反应的患者中，SF - 36 PF评分从32.2提高到78.3，DSQ - SF评分从71.1降至24.3。这6名患者中有5名有显著且持续的改善，随访结束时SF - 36 PF评分平均为88（范围80 - 95）。基线时每24小时平均步数为3359步（范围1493 - 6277步）。在8 - 9个月时，平均步数为5862步，6名有反应的患者为7392步。所有5名持续改善的患者在几周内平均步数达到10000步/24小时以上，个别日子超过15000步。6名临床改善患者的血清IgG水平相对降低了54%，4名无改善患者降低了40%。血液中基线自然杀伤细胞（NK）计数低与无临床反应显著相关。
10名ME/CFS患者皮下注射达雷妥尤单抗耐受性良好。在6名患者中，治疗与临床改善以及血清IgG水平的同时短暂降低相关，表明长寿浆细胞和功能性自身抗体具有重要的病理机制作用。在进行随机研究之前不应得出明确结论。
https://euclinicaltrials.eu，标识符：2022 - 000281 - 18。
