Efficacy of adjunct tacrolimus treatment in patients with rheumatoid arthritis with inadequate responses to methotrexate.

OBJECTIVES: We aimed to assess the efficacy of tacrolimus (TAC) as an add-on therapy in patients with rheumatoid arthritis (RA) who were previously treated with methotrexate (MTX) but not with biologics. METHODS: The study group (MTX + TAC group) consisted of 157 patients (selected from among the patients in the Institute of Rheumatology, Rheumatoid Arthritis [IORRA] RA cohort from April 2005 to October 2009) who received add-on therapy with TAC in addition to MTX, but without biologics. A propensity score (PS) for the use of TAC was derived, and 471 PS-matched patients who received MTX alone or MTX with other non-biologic disease-modifying antirheumatic drugs (except for TAC), but not with biologics, were selected and served as the control group. Changes in disease activity in the two groups during three consecutive IORRA phases were analyzed by adjusting for confounding factors. RESULTS: The median 28-joint disease activity score (DAS28) decreased from 4.58 to 3.70 in the MTX + TAC group and from 4.12 to 3.61 in the control group. After adjusting for confounding factors, the decrease in the DAS28 score in the MTX + TAC group was significantly larger (by 0.273 points) than that in the control group (P < 0.05). CONCLUSION: This study demonstrated the efficacy of add-on therapy with TAC to MTX in patients with RA in daily practice.

Incidence of serious respiratory infections in patients with rheumatoid arthritis treated with tocilizumab.

We aimed to demonstrate the incidence of serious respiratory infections in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ) monotherapy. We analyzed the incidence of serious respiratory infections in 601 RA patients enrolled in TCZ clinical trials and their extension studies (TCZ cohort) and in 601 age- and sex-standardized RA patients treated in daily clinical practice at Tokyo Women's Medical University (IORRA subsample cohort). The rates of serious respiratory infections were 1.77 per 100 patient-years from 1999 to 2008 in the TCZ cohort and 0.53 per 100 patient-years from 2000 to 2009 in the IORRA subsample cohort. With the IORRA subsample cohort regarded as a standard population, the standardized incidence ratio (SIR) of serious respiratory infection in the TCZ cohort was 3.64 [95% confidence interval (CI) 2.56-5.01], standardized for age and sex; 2.35 (95% CI 1.66-3.24), standardized for age sex, and corticosteroid use; 1.85 (95% CI 1.30-2.55), standardized for age sex, and pre-existing pulmonary involvement; and 2.41 (95% CI 1.68-3.34) standardized for age sex, and disease activity. The risk of serious respiratory infection in the TCZ cohort was approximately double that in the IORRA subsample cohort after standardizing for corticosteroid use, pre-existing pulmonary involvement, or disease activity. This is comparable to the risk reported when tumor necrosis factor (TNF) inhibitors are used.

Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis.

The objective of this study was to assess the usefulness of tacrolimus (TAC) for rheumatoid arthritis (RA) patients. The first 101 consecutive RA patients in whom TAC treatment was initiated were prospectively registered and their data analyzed. Clinical variables were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The 101 patients included 85 females and 16 males. Average doses of TAC were 1.62 mg/day at entry and 2.13 mg/day at month 12. The average doses of concomitantly prescribed prednisolone (6.92 mg/day) and methotrexate (MTX; 8.59 mg/week) were higher than those in all RA patients in the IORRA cohort. At month 12, 57 patients remained on TAC therapy; 18 patients had discontinued TAC due to side effects, and 16 patients had discontinued due to inefficacy. Adverse reactions responsible for discontinuation included gastrointestinal symptoms, renal dysfunction, and infection. According to the European League Against Rheumatism (EULAR) response criteria, 56.5% of the patients who continued TAC at 12 months experienced "good" or "moderate" responses. Through the use of last observation carried forward (LOCF) methodology, the average Disease Activity Score (DAS) 28 significantly improved. We confirmed the usefulness of TAC for the treatment of RA and found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.

Evaluation of Pneumocystis pneumonia infection risk factors in patients with connective tissue disease.

We conducted a retrospective, clinical evaluation of connective tissue disease (CTD) patients who were tested for either sputum or bronchoalveolar lavage fluid Pneumocystis polymerase chain reaction (PC-PCR) and analyzed the risk factors that cause Pneumocystis pneumonia (PCP) susceptibility and fatality. PC-PCR was performed on 66 CTD patients who presented with symptoms, data, or radiological findings strongly suggesting respiratory infection. Patients with higher oral corticosteroid doses, use of oral methotrexate (MTX), bilateral lung findings, positive beta-D-glucan, and no prophylaxis use were more susceptible to PCP. They had significantly low immunoglobulin G and significantly high beta-D-glucan and lactate dehydrogenase. Survivors and nonsurvivors of PCP were also evaluated. Poor prognoses were observed with older age, elevated beta-D-glucan, rheumatoid arthritis (RA) patients using MTX, hypoxemia, bilateral lung findings, and mechanical ventilation use. Nonsurvivors had significantly lower lymphocytes, oxygen saturation, and significantly higher beta-D-glucan. In RA, poor prognoses were seen with those taking MTX. Disease duration, underlying pulmonary complications, and oral corticosteroid doses did not lead to poor prognoses in RA. Because PCP in CTD leads to abrupt onset of symptoms with poor survival rates, early diagnosis and initiation of treatment are critical, and it is essential for clinicians to recognize risk factors that predispose patients to PCP and its mortality.