Rheumatology Division, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Sao Paulo, Brazil.
Pediatric Rheumatology Division, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, Sao Paulo, Brazil.
Ann Rheum Dis. 2022 Jun;81(6):889-897. doi: 10.1136/annrheumdis-2021-221916. Epub 2022 Feb 22.
To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA).
This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice.
Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024).
We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.
评估在接种科兴新冠疫苗后每剂药物中停止使用 2 周甲氨蝶呤（MTX）与维持 MTX 治疗相比，对类风湿关节炎（RA）患者的免疫原性和安全性的影响。
这是一项单中心、前瞻性、随机、研究者设盲、干预研究（NCT04754698，CoronavRheum），纳入了稳定的临床疾病活动指数（CDAI）≤10、泼尼松≤7.5mg/天的成年 RA 患者，按 1:1 比例随机（MTX-hold）组在每剂疫苗后停止使用 MTX 2 周或维持 MTX（MTX-maintain）治疗，在第 0 天（D0）、D28 和 D69 进行评估。主要结局是在 D69 时抗 SARS-CoV-2 S1/S2 IgG 血清转化率（SC）和中和抗体（NAb）阳性。次要结局是几何平均滴度（GMT）和爆发率。对于免疫原性分析，我们排除了基线 IgG/NAb 阳性的患者，出于安全原因，排除了 D28 时爆发（CDAI>10）且两次未停止使用 MTX 的患者。
随机化纳入了 138 名患者，其中 9 名患者被排除（5 例 COVID-19，4 例违反方案）。安全性评估纳入了 MTX-hold 组的 60 名患者和 MTX-maintain 组的 69 名患者。进一步排除了 27 名患者（13 名（21.7%）与 14 名（20.3%），p=0.848）基线 IgG/NAb 阳性和 10 名 MTX-hold 患者 D28 时 CDAI>10。在 D69 时，MTX-hold 组（n=37）的 SC 率高于 MTX-maintain 组（n=55）（29（78.4%）与 30（54.5%），p=0.019），GMT 也相应增加（34.2（25.2-46.4）与 16.8（11.9-23.6），p=0.006）。NAb 阳性率无差异（23（62.2%）与 27（49.1%），p=0.217）。在 D28 时爆发，两组的发生率相似（CDAI，p=0.122；C 反应蛋白的 28 个关节疾病活动评分，p=0.576），而 MTX-hold 在 D69 时 CDAI>10 的发生率更高（p=0.024）。
我们提供了新的数据，即科兴新冠疫苗每剂药物后停止使用 2 周 MTX 可提高抗 SARS-CoV-2 IgG 反应。第二次 MTX 停药后爆发率增加可能与疫苗剂量之间的短期间隔有关。由于可能出现爆发，这种策略需要密切监测和共同决策。
