Comparable efficacy of denosumab and romosozumab in patients with rheumatoid arthritis receiving glucocorticoid administration.

OBJECTIVES: Romosozumab is a newly released and widely known molecular-targeted drug for severe osteoporosis treatment with comparable effectiveness to denosumab. However, there have been no reports discussing the efficacy of those treatments for rheumatoid arthritis (RA) patients, especially those receiving glucocorticoids. This retrospective observational registry study compared the efficacy of 12-month treatment of denosumab and romosozumab in RA patients under the influence of glucocorticoid intake. METHODS: Following propensity score matching, 36 patients each in the denosumab and romosozumab groups were analysed in this study. Drug effectiveness was evaluated by measuring bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at baseline, 6 and 12 months as well as alterations in P1NP, TRACP-5b, and simplified disease activity index (SDAI). The occurrence of adverse events and new fractures was also assessed. RESULTS: At 12 months of treatment, BMD at the lumbar spine was increased by 7.5% in the denosumab group and 8.7% in the romosozumab group, which were both significantly and comparably elevated over baseline. At the total hip and femoral neck, romosozumab tended to exhibit favourable efficacy to increase BMD versus denosumab. Both P1NP and TRACP-5b were significantly lower in the denosumab group as compared with the baseline. Conversely in the romosozumab group, P1NP was increased over baseline, while TRACP-5b was decreased. Regarding SDAI alterations, both the romosozumab and denosumab groups exhibited comparable improvements in RA disease activity over time during treatment. Recorded adverse events and new fractures during treatment were few and minor in both groups. CONCLUSIONS: Romosozumab exhibited comparable efficacy to denosumab for increasing BMD even under the influence of glucocorticoids for treating RA. Both drugs may be therefore suitable for managing osteoporosis in patients with RA and glucocorticoid intake.

Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab: An interventional study.

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX.Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36.Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1-18.4%; p= .025).Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.

Mechanical stress loading induces CD44 cleavage in human chondrocytic HCS-2/8 cells.

Although excessive mechanical stress loading is known to induce articular cartilage degradation, the mechanism underlying this process is unclear. The interaction between hyaluronan (HA) and its primary receptor CD44 maintains the homeostasis of articular chondrocytes. CD44 cleavage and the generation of CD44-intracellular domain (ICD) can lead to the loss of extracellular matrices in chondrocytes. Here we studied the effects of cyclic tensile strain (CTS) loading, a representative mechanical stress, on CD44 cleavage. CTS loading (1 Hz and 20% elongation for 48 h) increased ADAM10 expression and CD44 cleavage in HCS-2/8 cells, a human chondrocytic cell line. Co-treatment with a chemical ADAM10 inhibitor significantly suppressed CTS loading-induced CD44 cleavage. Chemical inhibition of transient receptor potential vanilloid 4 (TRPV4) significantly suppressed CTS loading-induced ADAM10 expression and CD44 cleavage. Conversely, chemical activation of TRPV4 increased ADAM10 expression and enhanced CD44 cleavage. Our findings suggest that CTS loading significantly increases the expression of ADAM10, which in turn enhances CD44 cleavage in HCS-2/8 cells. The primary mechanoreceptor mediating this process is TRPV4. This signature event could provide an avenue for intervention in the prevention of cartilage degradation leading to OA.

Drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors for rheumatoid arthritis in Japanese patients on low-dose methotrexate or without methotrexate.

OBJECTIVES: The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX. METHODS: A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents. RESULTS: Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model. CONCLUSIONS: Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.

A review of tocilizumab treatment in 122 rheumatoid arthritis patients included in the Tsurumai Biologics Communication Registry (TBCR) Study.

OBJECTIVES: Biologics have transformed the treatment of rheumatoid arthritis. Clinical remission is now the goal. We sought to verify whether the administration of tocilizumab-a biologic-can help to achieve current treatment goals. METHODS: Using data from the Tsurumai Biologics Communication Registry for 122 patients treated with tocilizumab, we evaluated changes in DAS28-ESR at 12 months after initiation, and also evaluated remission rates defined using conventional and new Boolean-based remission criteria. We divided 50 patients who had received tocilizumab as a first-line treatment into two groups [disease duration at baseline of 12 months or less (≤12 M) and more than 12 months (>12 M)]. RESULTS: At 12 months after initiation, there was no difference in DAS28-ESR, and remission rates based on the conventional criterion were also comparable (50 % in both groups). However, under the new criterion, remission was 50.0 % in the ≤12 M group against 12.5 % in the >12 M group (p = 0.0181). Among the individual components of the new remission criterion, the small proportion of patients in the >12 M group with a patient global assessment (PtGA) of ≤1 had a particularly strong influence on the remission rate for that group, but this component was not as important for the ≤12 M group. CONCLUSIONS: When used as a first-line biological drug for patients with early-stage RA (≤12 M), tocilizumab appears to provide high rates of remission under the Boolean-based remission criterion, which were strongly affected by the PtGA.

Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study.

Romosozumab is a potent drug for treating postmenopausal osteoporosis but has a limited dosing period of 12 months. Bone mineral density (BMD) decreases soon after romosozumab discontinuation, thus emphasizing the importance of appropriate sequential treatment. The present VICTOR randomized controlled study compared the efficacy of ibandronate and denosumab as sequential therapy options following 12-month romosozumab treatment. Subjects completing 12 months of romosozumab administration for severe postmenopausal osteoporosis were randomly assigned to receive either ibandronate or denosumab for an additional 12 months. The primary outcome of interest was the percentage changes in BMD at the lumbar spine, total hip, and femoral neck from 12 months (completion of romosozumab) to 18 and 24 months of total treatment (6 and 12 months, respectively, after the conversion to sequential therapy). Secondary outcomes included alterations in serum bone turnover markers and the incidence of adverse events. Sixty-two subjects each in the ibandronate and denosumab groups completed the sequential therapy. The respective percentage changes in BMD at the lumbar spine from 12 months to 24 months were 2.5 % in the ibandronate group and 5.4 % in the denosumab group. At 24 months, we observed significant differences versus 12 months for both groups as well as between the groups (all P < 0.01), showing a superior ability to increase BMD at the lumbar spine for denosumab over ibandronate. BMD gains at the total hip and femoral neck exhibited comparably favorable trends. P1NP and TRACP-5b were significantly decreased from 12 to 24 months (-64.9 % and - 26.8 % in the ibandronate group and - 67.4 % and - 36.3 % in the denosumab group, respectively; all P < 0.001 versus 12 months). Several minor adverse events were recorded in both groups, none of which led to the discontinuation of the trial. The VICTOR study revealed that denosumab could be considered more effective than ibandronate, with few severe adverse events, for the enhancement of BMD as a sequential agent after romosozumab in postmenopausal osteoporosis patients.

Effects of romosozumab with and without active vitamin D analog supplementation for postmenopausal osteoporosis.

BACKGROUND & AIMS: Although romosozumab is attracting attentions as one of favorably used drugs in today's osteoporosis treatment, there has been no report discussing the differences in the efficacy of romosozumab in the presence or absence of combined use of active vitamin D analog yet. This prospective cohort investigation compared the effects of 12-month romosozumab treatment to increase bone mineral density (BMD) for postmenopausal osteoporosis to observe the influence of combined vitamin D supplementation. METHODS: During 12-month romosozumab treatment, 175 patients were divided into the VD group (with vitamin D analog: N = 88) and the NVD group (without vitamin D analog: N = 87), and the change in BMD from baseline was measured at 6 and 12 months as well as alterations in bone turnover markers, serum calcium, and the incidence of adverse events during the administration period. RESULTS: The average 12-month percentage change from baseline level for lumbar spine BMD was comparable at 12.3% in the VD group and 12.1% in the NVD group. The changes in BMD at the total hip and femoral neck showed no significant differences between the groups. The VD group exhibited a significantly smaller increase in procollagen type 1 N-terminal propeptide 1 (P1NP) and larger decrease in tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) versus the NVD group. The reduction rate of serum-corrected calcium was significantly less in the VD group than in the NVD group. Adverse events were minor in both groups, with no significant difference in the frequency of new fractures. CONCLUSION: Romosozumab may significantly increase BMD regardless of the addition of an active vitamin D analog.

Real-world effects and adverse events of romosozumab in Japanese osteoporotic patients: A prospective cohort study.

Real-world data on the new anti-sclerostin antibody drug, romosozumab, remain scarce. There is a strong need to accumulate and analyze data on romosozumab treatment for such conditions as osteoporosis. The purpose of this study was to investigate the therapeutic and adverse effects of romosozumab for osteoporosis treatment in clinical practice. Of the 230 osteoporosis patients prescribed romosozumab from September 2019 in this prospective multicenter cohort study, 204 patients completed 12 months of treatment. The primary outcome of interest was the rate of change in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck as measured by dual-energy X-ray absorptiometry. Secondary outcomes included changes in bone turnover markers and serum-corrected calcium level as well as the incidence of adverse events. At 6 and 12 months of romosozumab treatment, the respective percentage change in BMD from baseline was 7.4% and 12.2% for the lumbar spine, 1.8% and 5.8% for the total hip, and 2.9% and 6.0% for the femoral neck, all of which were significantly higher (P < 0.001) than baseline values. Patients who switched from another osteoporosis regimen exhibited significantly lower lumbar spine BMD gains versus treatment-naïve patients, especially for cases switching from denosumab. P1NP was significantly increased at 6 months (58.9%; P < 0.01), while TRACP-5b was significantly decreased at 6 months (-14.7%; P < 0.001) and 12 months (-18.8%; P < 0.001) versus baseline values. The largest rate of decrease in serum-corrected calcium was 3.7% at 12 months. Sixty-four (27.8%) of 230 patients experienced an adverse event, and 7 (3.0%) new fractures were recorded. In sum, romosozumab treatment for 12 months significantly improved lumbar spine, total hip, and femoral neck BMD according to real-world data.

Denosumab versus romosozumab for postmenopausal osteoporosis treatment.

Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable difference in the incidence of new vertebral fractures. Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.

Comparison of the effects of baricitinib and tocilizumab on disease activity in patients with rheumatoid arthritis: a propensity score matching analysis.

OBJECTIVE: This study aimed to compare the effects of baricitinib, a Janus kinase inhibitor, and tocilizumab, a monoclonal anti-interleukin-6 receptor antibody, on disease activity in patients with rheumatoid arthritis (RA), and to investigate the influence of inflammation on improvement in patient global assessment (PGA) of disease activity. METHODS: This study was performed based on data from a multicenter registry, and included 284 and 113 patients treated with tocilizumab and baricitinib, respectively, who were observed for longer than 24 weeks. Propensity score matching was performed to address potential treatment-selection bias. To assess the influence of inflammation on PGA, patients were divided into two groups based on whether or not they achieved improvement in C-reactive protein (CRP, an objective marker of inflammation) at 24 weeks. RESULTS: A total of 48 matched pairs of patients were identified. Compared to treatment with tocilizumab, baricitinib showed a similar improvement in tender and swollen joint count and serum CRP levels, and a significantly greater improvement in PGA at 24 weeks. As a result, the baricitinib group had a significantly higher proportion of patients who achieved Boolean remission at 24 weeks. In subgroups of patients who did not achieve 50% or 70% CRP improvement, significant decreases from baseline to 24 weeks were observed in PGA in patients treated with baricitinib, but not in those treated with tocilizumab. CONCLUSION: Compared to tocilizumab, baricitinib significantly improved PGA despite similar effects on inflammation in patients with RA. Moreover, the influence of inflammation on PGA improvement differed between baricitinib and tocilizumab. Key-points • Baricitinib and tocilizumab had similar effects on inflammation in RA patients. • Baricitinib improved patient global assessment (PGA) more than tocilizumab. • Baricitinib had a higher Boolean remission rate than tocilizumab at 24 weeks. • Influence of inflammation on PGA improvement differed between the two drugs.

Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry.

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan-Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab.

OBJECTIVE: To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. METHODS: Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI]≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models. RESULTS: Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6-81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72-83.80) were independent predictors of disease flare. CONCLUSION: Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. TRIAL REGISTRATION NUMBER: jRCTs041180071, UMIN000021247.

Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading.

CD44 fragmentation is enhanced in chondrocytes of osteoarthritis (OA) patients. We hypothesized that mechanical stress-induced enhancement of CD44-intracellular domain (CD44-ICD) production plays an important role in the de-differentiation of chondrocytes and OA. This study aimed to assess the relationship between CD44-ICD and chondrocyte gene expression. Monolayer cultured primary bovine articular chondrocytes (BACs) were subjected to cyclic tensile strain (CTS) loading. ADAM10 inhibitor (GI254023X) and γ-secretase inhibitor (DAPT) were used to inhibit CD44 cleavage. In overexpression experiments, BACs were electroporated with a plasmid encoding CD44-ICD. CTS loading increased the expression of ADAM10 and subsequent CD44 cleavage, while decreasing the expression of SOX9, aggrecan, and type 2 collagen (COL2). Overexpression of CD44-ICD also resulted in decreased expression of these chondrocyte genes. Both GI254023X and DAPT reduced the production of CD44-ICD upon CTS loading, and significantly rescued the reduction of SOX9 expression by CTS loading. Chemical inhibition of CD44-ICD production also rescued aggrecan and COL2 expression following CTS loading. Our findings suggest that CD44-ICD is closely associated with the de-differentiation of chondrocytes. Excessive mechanical stress loading promoted the de-differentiation of BACs by enhancing CD44 cleavage and CD44-ICD production. Suppression of CD44 cleavage has potential as a novel treatment strategy for OA.

＜Editors' Choice＞ Ultrasound measurement of thigh muscle thickness for assessment of sarcopenia.

Our aim of this study is to compare the thigh muscle thickness measurements obtained using ultrasound and bioelectrical impedance analysis (BIA) methods, and to investigate the validity and cutoff value of the ultrasonography. We analyzed a total of 201 participants (99 male and 102 female participants, mean age, 66.2 years) participated in the annual health checkup in the Yakumo Study, 2014. Thigh muscle thickness (TMT, sum of the rectus femoris and vastus intermedius muscle thickness) was measured using ultrasound at mid-thigh in the sitting position. Appendicular skeletal muscle mass (aSMI) was measured using BIA. Cutoff value of TMT was determined through the receiver operating characteristic analysis. We defined sarcopenia with the diagnostic algorithm of Asian Working Group for Sarcopenia. TMT was significantly reduced in subject with sarcopenia than in those without sarcopenia in both gender. Muscle measurements obtained using the BIA methods (aSMI) and ultrasound methods (TMT) showed a significant correlation, with a correlation coefficient of 0.38 (P < 0.001). Cutoff value, sensitivity, and specificity of TMT in diagnosis of muscle loss were 36 mm, 72.0%, and 73.9%, respectively, for the male participants, and 34 mm, 72.2%, and 72.4%, respectively, for the female participants. In conclusion, the ultrasonography for thigh muscle might be a simple diagnostic method for sarcopenia.

Golimumab reduces disease activity of rheumatoid arthritis for 1 year and strongly inhibits radiographic progression in Japanese patients: partial but detailed results of the GO-FORTH and GO-MONO studies.

The objective of this study is to evaluate the efficacy of golimumab (GLM) in Japanese patients with active rheumatoid arthritis (RA) for 1 year. Nineteen patients were enrolled; 9 were randomized to the placebo (PBO) + methotrexate (MTX), GLM 50 mg + MTX, or GLM 100 mg + MTX therapy group; and 10 were randomized to the PBO, GLM 50 mg, or GLM 100 mg therapy group. One patient in the GLM 100 mg + MTX therapy group with median values from the GO-FORTH study was added. Data were evaluated by assessing the changes in DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI), and total Sharp score (TSS) at week 52. Mean changes in DAS28-ESR in the MTX monotherapy, GLM 50 mg + MTX, GLM 100 mg + MTX, PBO, GLM 50 mg, and GLM 100 mg therapy groups were -2.70, -2.57, -2.27, -0.60, -2.53, and -2.53, respectively; the mean improvements in HAQ-DI were 0.188, 0.708, 0.377, 0.188, 1.042, and 0.625, respectively. The mean changes in TSS were 1.63, -0.33, -1.17, 4.25, 1.00, and 1.67, respectively. A significant difference was only observed in the mean TSS change between the PBO + MTX and the GLM 100 mg + MTX groups. However, in terms of mean changes in DAS28-ESR in the combination therapy groups, PBO + MTX therapy seemed to elicit similar results as the GLM 50 mg + MTX and GLM 100 mg + MTX therapies (no significant difference) because all four patients in the PBO + MTX therapy group may have received GLM from week 24 as a crossover. Combined GLM + MTX therapy reduced disease activity and strongly inhibited radiographic disease progression in patients with active RA at week 52.

A Fatal Case of Relapsing Pneumonia Caused by Legionella pneumophila in a Patient with Rheumatoid Arthritis After Two Injections of Adalimumab.

We present a rare fatal case of relapsing pneumonia caused by Legionella pneumophila in a patient with rheumatoid arthritis after only two injections of adalimumab. A 78-year-old Japanese woman with a 14-year history of rheumatoid arthritis was prescribed adalimumab because her disease activity remained high. However, 8 days after her second injection of adalimumab, she was admitted to our hospital and diagnosed with pneumonia caused by L. pneumophila. Following intravenous antibiotic therapy, she recovered completely from pneumonia and was discharged on day 10, but pneumonia relapsed, resulting in death 79 days after the first episode of pneumonia. L. pneumophila can lead to recurrence of pneumonia that can ultimately prove fatal, similar to the present case. A review of the pertinent literature is also presented.