BackgroundSulfamethoxazole-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.MethodsAdult 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.ResultsOf 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.ConclusionsAlthough 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 registrationThe University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727, registered 10 April 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1206-8) contains supplementary material, which is available to authorized users.

A 47-year-old Japanese woman developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) complicated by a rare combination of aortitis and hypertrophic pachymeningitis. Despite the therapy with prednisolone and cyclophosphamide, the aortitis was not ameliorated. However, after cyclophosphamide was replaced with intravenous tocilizumab, the aortitis was improved, and the prednisolone dose was successfully tapered to 4 mg/day without elevation in C-reactive protein and myeloperoxidase ANCA (MPO-ANCA) levels. Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis. On the other hand, we succeeded to improve the aortitis in AAV with monthly administration of tocilizumab. Moreover, we successfully controlled disease activity and enabled the tapering of prednisolone to 4 mg/day without relapses of AAV symptoms and elevated MPO-ANCA levels. It indicates that tocilizumab may be therapeutically beneficial for not only aortitis but also AAV itself. In conclusion, tocilizumab was effective in treating glucocorticoid- and cyclophosphamide-resistant AAV-associated aortitis. This is the first report demonstrating the successful treatment of AAV-associated aortitis using tocilizumab.

Abstract Objectives To investigate long-term prophylactic efficacy, drug retention, and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) prophylaxis against Pneumocystis pneumonia (PCP). Methods Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily), and escalation group (ES; starting at 40/8 mg and increased incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, was reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate, and adverse events (AEs). Results Fifty-eight, 59, and 55 patients in the SS, HS, and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8–100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7% vs 47.2%, p = 0.004). The discontinuation rates due to AEs were significantly lower in HS (19.1%, p = 0.007) and ES (20.3%, p = 0.007) than in SS (41.8%). The IRs of AEs requiring SMX/TMP dose reduction through week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES (p = 0.007). Conclusion SMX/TMP 200/40 mg had a high PCP prevention rate and is superior to SMX/TMP 400/80 mg in terms of drug retention and safety.

summaryA 35-year-old woman was admitted to a hospital because of fever, sore throat, cervical lymph node swelling, and skin rashes. Laboratory data revealed leukocytosis and elevated C-reactive protein (CRP), aspartate aminotransferase, alanine aminotransferase, and ferritin levels. No antinuclear antibody or rheumatoid factor was found. She was diagnosed as having adult-onset Still's disease (AOSD). Although treatment with high-dose glucocorticoid (GC) and cyclosporine (CsA) was started, her condition did not improve because of complication with severe hemophagocytic syndrome (HPS). Therefore, she was transferred to our hospital. Immediately after admission, GC pulse therapy was started again, and treatment with CsA was replaced with tacrolimus (TAC), in addition, plasma exchange therapy was initiated. After treatment, her condition improved. However, 1 week after plasma exchange was discontinued, her condition deteriorated slightly with a slight fever and elevation of CRP level. This indicated that her condition could not be managed with GC and TAC, therefore, tocilizumab (TCZ) was added to her treatment, which improved her symptoms and enabled reduction in GC and TAC doses. Although many reports have indicated that biological agents are eŠective for refractory AOSD, their safety and e‹cacy in cases of AOSD complicated with HPS are controversial as these agents may exacerbate HPS. Our present case indicates that TCZ can be used after control of the disease activity by plasma exchange against refractory AOSD complicated with HPS.