Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

被引：41

作者：

Utsunomiya, Masako ^{[1
,2
,3
]}

Dobashi, Hiroaki ^{[4
]}

Odani, Toshio ^{[5
,18
]}

Saito, Kazuyoshi ^{[6
]}

Yokogawa, Naoto ^{[7
]}

Nagasaka, Kenji ^{[1
,2
,8
]}

Takenaka, Kenchi ^{[2
,8
]}

Soejima, Makoto ^{[8
,19
]}

Sugihara, Takahiko ^{[9
]}

Hagiyama, Hiroyuki ^{[10
]}

Hirata, Shinya ^{[11
]}

Matsui, Kazuo ^{[12
,20
]}

Nonomura, Yoshinori ^{[13
]}

Kondo, Masahiro ^{[14
]}

Suzuki, Fumihito ^{[15
,21
]}

Tomita, Makoto ^{[16
]}

Kihara, Mari ^{[12
]}

Yokoyama, Waka ^{[1
,2
]}

Hirano, Fumio ^{[1
,2
]}

Yamazaki, Hayato ^{[1
,2
]}

Sakai, Ryoko ^{[1
,2
,17
]}

Nanki, Toshihiro ^{[1
,2
,22
]}

Koike, Ryuji ^{[1
,2
]}

Kohsaka, Hitoshi ^{[2
]}

Miyasaka, Nobuyuki ^{[2
]}

Harigai, Masayoshi ^{[1
,2
,17
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pharmacovigilance, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Rheumatol, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan

[3] Musashino Red Cross Hosp, Dept Rheumatol, 1-26-1 Kyonancho, Tokyo 1800023, Japan

[4] Kagawa Univ, Div Hematol Rheumatol & Resp Med, Dept Internal Med, Fac Med, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan

[5] Obihiro Kosei Gen Hosp, Dept Internal Med 3, West 6,South 8, Obihiro, Hokkaido 0800016, Japan

[6] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 1, Yahata Nishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan

[7] Tokyo Metropolitan Tama Med Ctr, Dept Rheumat Dis, 2-8-29 Musashidai, Fuchu, Tokyo 1838524, Japan

[8] Ome Municipal Gen Hosp, Dept Rheumatol, 4-16-5 Higashi Ome, Tokyo 1980042, Japan

[9] Tokyo Metropolitan Geriatr Hosp, Dept Med & Rheumatol, Itabashi Ku, 35-2 Sakaecho, Tokyo 1730015, Japan

[10] Yokohama City Minato Red Cross Hosp, Dept Rheumatol, Naka Ku, 3-12-1 Shinyamashita, Yokohama, Kanagawa 2318682, Japan

[11] Kumamoto Univ, Grad Sch Med, Dept Hematol Rheumatol & Infect Dis, 1-1-1 Honjo, Kumamoto, Kumamoto 8608556, Japan

[12] Kameda Med Ctr, Dept Rheumatol, 929 Higashi Cho, Chiba 2968602, Japan

[13] Tokyo Kyosai Hosp, Dept Rheumatol, Meguro Ku, 2-3-8 Nakameguro, Tokyo 1538934, Japan

[14] Shimane Univ, Dept Rheumatol, Fac Med, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan

[15] Soka Municipal Hosp, Dept Rheumatol, 2-21-1 Soka, Soka, Saitama 3400043, Japan

[16] Tokyo Med & Dent Univ, Clin Res Ctr, Hosp Med, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138549, Japan

[17] Tokyo Womens Med Univ, Inst Rheumatol, Div Epidemiol & Pharmacoepidemiol Rheumat Dis, Shinjuku Ku, 10-22 Kawada Cho, Tokyo 1620054, Japan

[18] Hokusei Hosp, Dept Internal Med, 5-1-1 Seiryu, Chitose, Hokkaido 0660081, Japan

[19] Soka Municipal Hosp, Dept Rheumatol, 2-21-1 Soka, Soka, Saitama 3408560, Japan

[20] Takikawa Municipal Hosp, Dept Internal Med, 2-2-34 Oh Machi, Takikawa, Hokkaido 0730022, Japan

[21] JA Toride Med Ctr, Dept Rheumatol, 2-1-1 Hongo, Toride, Ibaraki 3020022, Japan

[22] Toho Univ, Dept Internal Med, Div Rheumatol, Ota Ku, 6-11-1 Omori Nishi, Tokyo 1438541, Japan

来源：

ARTHRITIS RESEARCH & THERAPY | 2017年 / 19卷

关键词：

Pneumocystis pneumonia; Sulfamethoxazole-trimethoprim; Prophylaxis; Efficacy; Safety; Drug discontinuation rate; Rheumatic disease; Randomized controlled trial; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CARINII-PNEUMONIA; JIROVECII PNEUMONIA; PRIMARY PROPHYLAXIS; AEROSOLIZED PENTAMIDINE; JAPANESE PATIENTS; ARTHRITIS; INFLIXIMAB; EFFICACY; SAFETY;

D O I：

10.1186/s13075-016-1206-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported. Methods: Adult patients with systemic rheumatic diseases who started prednisolone >= 0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24. Results: Of 183 patients randomly allocated at a 1: 1: 1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8-100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS (p = 0.007). The discontinuation rates due to AEs were significantly lower with HS (p = 0.006) and ES (p= 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP (p = 0.009) and AEs of special interest (p = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES. Conclusions: Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases.

引用

页数：10

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