PMID- 28100282
OWN - NLM
STAT- MEDLINE
DCOM- 20171121
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Jan 18
TI  - Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of 
      Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from 
      a non-blinded, randomized controlled trial.
PG  - 7
LID - 10.1186/s13075-016-1206-8 [doi]
LID - 7
AB  - 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. TRIAL REGISTRATION: The University 
      Hospital Medical Information Network Clinical Trials Registry number is 
      UMIN000007727 , registered 10 April 2012.
FAU - Utsunomiya, Masako
AU  - Utsunomiya M
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
AD  - Department of Rheumatology, Musashino Red Cross Hospital, 1-26-1 Kyonancho, 
      Musashino, Tokyo, 180-0023, Japan.
FAU - Dobashi, Hiroaki
AU  - Dobashi H
AD  - Department of Internal Medicine, Division of Hematology, Rheumatology and 
      Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, 
      Miki-cho, Kida-gun, Kagawa, 761-0793, Japan.
FAU - Odani, Toshio
AU  - Odani T
AD  - Third Department of Internal Medicine, Obihiro-Kosei General Hospital, West-6, 
      South-8, Obihiro, Hokkaido, 080-0016, Japan.
AD  - Department of Internal Medicine, Hokusei Hospital, 5-1-1 Seiryu, Chitose, 
      Hokkaido, 066-0081, Japan.
FAU - Saito, Kazuyoshi
AU  - Saito K
AD  - First Department of Internal Medicine, School of Medicine, University of 
      Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, 
      Kitakyushu, Fukuoka, 807-8555, Japan.
FAU - Yokogawa, Naoto
AU  - Yokogawa N
AD  - Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29 
      Musashidai, Fuchu, Tokyo, 183-8524, Japan.
FAU - Nagasaka, Kenji
AU  - Nagasaka K
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
AD  - Department of Rheumatology, Ome Municipal General Hospital, 4-16-5 Higashi-Ome, 
      Ome, Tokyo, 198-0042, Japan.
FAU - Takenaka, Kenchi
AU  - Takenaka K
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
AD  - Department of Rheumatology, Ome Municipal General Hospital, 4-16-5 Higashi-Ome, 
      Ome, Tokyo, 198-0042, Japan.
FAU - Soejima, Makoto
AU  - Soejima M
AD  - Department of Rheumatology, Ome Municipal General Hospital, 4-16-5 Higashi-Ome, 
      Ome, Tokyo, 198-0042, Japan.
AD  - Department of Rheumatology, Soka Municipal Hospital, 2-21-1 Soka, Soka, Saitama, 
      340-8560, Japan.
FAU - Sugihara, Takahiko
AU  - Sugihara T
AD  - Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, 
      35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Hagiyama, Hiroyuki
AU  - Hagiyama H
AD  - Department of Rheumatology, Yokohama City Minato Red Cross Hospital, 3-12-1, 
      Shinyamashita, Naka-ku, Yokohama, Kanagawa, 231-8682, Japan.
FAU - Hirata, Shinya
AU  - Hirata S
AD  - Department of Hematology, Rheumatology, and Infectious Disease, Kumamoto 
      University Graduate School of Medicine, 1-1-1 Honjo, Kumamoto, Kumamoto, 
      860-8556, Japan.
FAU - Matsui, Kazuo
AU  - Matsui K
AD  - Department of Rheumatology, Kameda Medical Center, 929 Higashi-cho, Kamogawa, 
      Chiba, 296-8602, Japan.
AD  - Department of Internal Medicine, Takikawa Municipal Hospital, 2-2-34 Oh-machi, 
      Takikawa, Hokkaido, 073-0022, Japan.
FAU - Nonomura, Yoshinori
AU  - Nonomura Y
AD  - Department of Rheumatology, Tokyo Kyosai Hospital, 2-3-8 Nakameguro, Meguro-ku, 
      Tokyo, 153-8934, Japan.
FAU - Kondo, Masahiro
AU  - Kondo M
AD  - Department of Rheumatology, Faculty of Medicine, Shimane University, 89-1 
      Enya-cho, Izumo, Shimane, 693-8501, Japan.
FAU - Suzuki, Fumihito
AU  - Suzuki F
AD  - Department of Rheumatology, Soka Municipal Hospital, 2-21-1 Soka, Soka, Saitama, 
      340-0043, Japan.
AD  - Department of Rheumatology, JA Toride Medical Center, 2-1-1 Hongo, Toride, 
      Ibaraki, 302-0022, Japan.
FAU - Tomita, Makoto
AU  - Tomita M
AD  - Clinical Research Center, Medical Hospital of Tokyo Medical and Dental 
      University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8549, Japan.
FAU - Kihara, Mari
AU  - Kihara M
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Yokoyama, Waka
AU  - Yokoyama W
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Hirano, Fumio
AU  - Hirano F
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Yamazaki, Hayato
AU  - Yamazaki H
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Sakai, Ryoko
AU  - Sakai R
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
AD  - Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, 
      Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, 
      Shinjuku-ku, Tokyo, 162-0054, Japan.
FAU - Nanki, Toshihiro
AU  - Nanki T
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
AD  - Division of Rheumatology, Department of Internal Medicine, Toho University School 
      of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.
FAU - Koike, Ryuji
AU  - Koike R
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Kohsaka, Hitoshi
AU  - Kohsaka H
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Miyasaka, Nobuyuki
AU  - Miyasaka N
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan.
FAU - Harigai, Masayoshi
AU  - Harigai M
AD  - Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, 
      Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 
      113-8519, Japan. harigai.masayoshi@twmu.ac.jp.
AD  - Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo 
      Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, 
      Japan. harigai.masayoshi@twmu.ac.jp.
AD  - Division of Epidemiology and Pharmacoepidemiology of Rheumatic Diseases, 
      Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, 
      Shinjuku-ku, Tokyo, 162-0054, Japan. harigai.masayoshi@twmu.ac.jp.
LA  - eng
SI  - UMIN CTR/UMIN000007727
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170118
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Anti-Bacterial Agents)
RN  - 8064-90-2 (Trimethoprim, Sulfamethoxazole Drug Combination)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-Bacterial Agents/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunocompromised Host
MH  - Male
MH  - Middle Aged
MH  - Pneumonia, Pneumocystis/*immunology/*prevention & control
MH  - Rheumatic Diseases/*immunology
MH  - Trimethoprim, Sulfamethoxazole Drug Combination/*administration & dosage/adverse 
      effects
PMC - PMC5241919
OTO - NOTNLM
OT  - Drug discontinuation rate
OT  - Efficacy
OT  - Pneumocystis pneumonia
OT  - Prophylaxis
OT  - Randomized controlled trial
OT  - Rheumatic disease
OT  - Safety
OT  - Sulfamethoxazole-trimethoprim
EDAT- 2017/01/20 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/01/18
CRDT- 2017/01/20 06:00
PHST- 2016/08/26 00:00 [received]
PHST- 2016/12/08 00:00 [accepted]
PHST- 2017/01/20 06:00 [entrez]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/01/18 00:00 [pmc-release]
AID - 10.1186/s13075-016-1206-8 [pii]
AID - 1206 [pii]
AID - 10.1186/s13075-016-1206-8 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2017 Jan 18;19(1):7. doi: 10.1186/s13075-016-1206-8.