RESUMEN
Since its approval for the management of systemic lupus erythematosus (SLE), belimumab has been widely used. However, its pregnancy safety profile has been underinvestigated. We present the pregnancy outcomes of two cases of early placental exposure to belimumab and summarise the pregnancy outcomes in previous reports regarding placental exposure to belimumab. Case 1 describes a 27-year-old woman with an 18-year history of SLE and lupus nephritis class III. We introduced belimumab 19 months prior to conception to control her proteinuria and discontinued its use at 5 weeks and 5 days of gestation. Her lupus activity was stable throughout pregnancy, and at 37 weeks and 1 day of gestation, she delivered a healthy girl with no anomaly. At delivery, the girl was small for gestational age, but at the 1-year follow-up, there was no delay in her growth or any serious infection. Case 2 describes a 32-year-old woman with a 15-year history of SLE. We introduced belimumab 9 months prior to conception and discontinued its use at 7 weeks and 1 day of gestation. Although her lupus was well controlled without belimumab, a missed abortion occurred, which was possibly due to foetal factors. Although there is accumulating data on the safety of belimumab use during pregnancy, it seems necessary to cautiously use this medication in pregnant women, until further analyses are conducted.
Asunto(s)
Inmunosupresores , Lupus Eritematoso Sistémico , Femenino , Humanos , Embarazo , Adulto , Inmunosupresores/efectos adversos , Placenta , Resultado del Tratamiento , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Resultado del EmbarazoRESUMEN
Alternate-day glucocorticoid (GC) therapy is a treatment option that can reduce GC-associated adverse events. We investigated the safety and efficacy of alternate-day GC therapy in patients with immunoglobulin G4-related disease (IgG4-RD). Medical records of patients with IgG4-RD who were followed for at least one year at St. Luke's International Hospital, Tokyo, Japan, from 2004 to 2020 were reviewed. Patients who fulfilled comprehensive IgG4-RD diagnostic criteria were divided into alternate-day or daily GC treatment groups based on their treatment protocol. The effect of alternate-day GC therapy on glucocorticoid toxicity index (GTI) score was evaluated using multilinear analysis with adjustments for cumulative GC doses until each assessment point and propensity scores (PS) for alternate-day GC therapy. Kaplan-Meier curves and Cox proportional hazard models were used to assess the efficacy of alternate-day GC therapy for disease control. Among the 67 patients with IgG4-RD, patients with alternate-day (nâ =â 13) and daily (nâ =â 31) GC treatments were analyzed after excluding 23 ineligible patients. The median (interquartile range) age was 64 (60-70) years, 29 (65.9%) were male patients, 26 (59.1%) patients had positive biopsy results, and the median follow-up period was 1643 days. Significantly more patients with alternate-day GC treatment used concomitant immunosuppressants (11 [84.6%] vs 11 [35.5%]; Pâ =â .007). The alternate-day strategy significantly lowered the GTI score after adjusting for cumulative GC dose until the assessment and PS (adjusted coefficient: -29.5 [-54.3, -4.8], Pâ =â .021 at 12 months; -20.0 [-39.8, -0.1], Pâ =â .049 at 24 months). Serious infections were numerically less frequent in the alternate-day group (incidence ratio [95% confidence interval [CI]: 0.45 [0.05, 3.63], Pâ =â .45). Most patients (92.3%) in the alternate-day GC treatment group and all patients in the daily GC treatment group showed treatment responses in the remission induction therapy. The PS-adjusted hazard ratio of alternate-day GC treatment for disease flares was not significant (1.55 [0.53, 4.51]; Pâ =â .43). The alternate-day treatment strategy significantly reduced GC-related adverse events regardless of the cumulative GC dose. Alternate-day GC treatment is a feasible option for patients with IgG4-RD, without a significant increase in disease flares particularly when combined with immunosuppressants.
Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4 , Anciano , Femenino , Glucocorticoides , Humanos , Inmunoglobulina G/uso terapéutico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION/OBJECTIVES: Belimumab combined with mycophenolate mofetil has been proven to be effective for treating systemic lupus erythematosus (SLE) in several randomized controlled trials. Calcineurin inhibitors are also useful in controlling the activity of SLE. However, the safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. Therefore, the current single-center retrospective study aimed to analyze the safety/efficacy profile of belimumab-tacrolimus (B-T) combination therapy in patients with SLE. METHOD: Patients with SLE administered tacrolimus and belimumab during treatment were included in the study. Samples were analyzed for the drug retention rate, SLE flare rate, infection incidence rate, and glucocorticoid-sparing effect of the B-T combination therapy. RESULTS: Thirty-three patients with SLE were treated with B-T combination therapy at our institution. Four patients discontinued treatment due to insufficient response or adverse events. The drug retention rate was over 90% at week 52 and approximately 80% at day 1000. Only one patient developed serious infection. The lupus low disease activity state (LLDAS) achievement ratio was 9.1% on the day of initiation and improved to 64.0% at 52 weeks after initiation. SLE flares were observed in three patients (9.1%) in the first 52 weeks after initiation, and in five patients (15.2%) throughout the study period. A glucocorticoid-reducing effect was also observed in patients treated with B-T combination therapy. CONCLUSIONS: In most patients with SLE, B-T combination therapy is well tolerated with a good efficacy profile and glucocorticoid-reducing effect. Thus, B-T combination therapy represents a feasible option for patients with refractory lupus. Key Points ⢠The safety and effectiveness of belimumab-calcineurin inhibitor combination therapy have not been addressed. ⢠The drug retention rate of belimumab-tacrolimus combination therapy was over 90% at week 52 and around 80% on day 1000 ⢠Almost none of the patients suffered from severe infection after the initiation of belimumab-tacrolimus combination therapy. ⢠Belimumab-tacrolimus combination therapy is efficacious in suppressing lupus activity and achieving LLDAS.
Asunto(s)
Lupus Eritematoso Sistémico , Tacrolimus , Humanos , Tacrolimus/uso terapéutico , Glucocorticoides/uso terapéutico , Inhibidores de la Calcineurina/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inducido químicamente , Inmunosupresores/efectos adversosRESUMEN
OBJECTIVE: Long-term glucocorticoid use in SLE may have significant side effects; however, glucocorticoid discontinuation is occasionally associated with disease flare-ups. Therefore, we evaluated the risk factors for disease flares and the flare rate on glucocorticoid tapering in patients with prior severe organ involvement. METHODS: Data of patients with SLE with glucocorticoid tapering at our institution were retrospectively analysed. We divided the patients by the presence of prior severe organ involvement and compared flare rates after glucocorticoid discontinuation. Furthermore, we determined risk factors for flares after glucocorticoid discontinuation. RESULTS: In total, 309 patients with SLE were screened, 73 of whom met the inclusion criteria; 49 were classified as SLE with prior severe organ involvement. No significant differences were noted in the 52-week flare rate after glucocorticoid discontinuation between patients with and without prior severe organ involvement (16.7% vs 18.2%, p=1.0). Hypocomplementaemia, elevated anti-dsDNA antibody titres more than twice the upper limit of the laboratory reference range, positive anti-Smith/anti-ribonucleoprotein antibody, and use of any immunosuppressant on the day of glucocorticoid discontinuation were negatively associated with flare-free remission. CONCLUSIONS: Glucocorticoid discontinuation after gradual tapering can often be achieved in patients with SLE, even with prior severe organ involvement, especially when the disease is clinically and serologically stable.
Asunto(s)
Glucocorticoides , Lupus Eritematoso Sistémico , Anticuerpos Antinucleares , Glucocorticoides/efectos adversos , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
We evaluated whether thyroid function test (TFT) screening is warranted for patients with autoimmune rheumatic diseases (ARD) by comparing the incidence of hypothyroidism requiring treatment (HRT) in ARD patients and healthy controls (HCs). Medical records of 2307 ARD patients and 78,251 HCs for whom thyroid-stimulating hormone (TSH) levels were measured between 2004 and 2018 were retrospectively reviewed. Cumulative incidence of HRT in ARD patients and HCs was compared. HRT development was evaluated with age- and sex-adjusted Kaplan-Meier curve. Risk factors were identified with Cox proportional hazard models. HRT was significantly more common in ARD patients than in HCs (6.3% vs. 1.9%, P < 0.001). After adjusting for age, sex, and baseline TSH level, hazard ratios for HRT were significantly higher in overall ARD patients (hazard ratio [95% confidence interval] 3.99 [3.27-4.87]; P < 0.001), particularly with rheumatoid arthritis and antinuclear antibody-associated diseases in female, and antinuclear antibody-associated diseases, spondyloarthritis, and vasculitis in male patients. Baseline high TSH level, thyroid-related autoantibody positivity, high IgG, and renal impairment were significant risk factors for hypothyroidism development in ARD patients; 20% of high-risk patients developed HRT during follow-up. HRT was significantly more frequent in ARD patients. Careful TFT screening and follow-up could help detecting clinically important hypothyroidism.
Asunto(s)
Artritis Reumatoide/sangre , Enfermedades Autoinmunes/sangre , Hipotiroidismo/sangre , Enfermedades Reumáticas/sangre , Tirotropina/sangre , Artritis Reumatoide/complicaciones , Artritis Reumatoide/patología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/patología , Estudios de Casos y Controles , Femenino , Humanos , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico , Hipotiroidismo/patología , Inmunoglobulina G/sangre , Riñón/metabolismo , Riñón/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/patología , Factores de Riesgo , Pruebas de Función de la TiroidesRESUMEN
AIM: Pre-administration screening of active infections is imperative for the safe use of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). However, a standardized screening method is lacking. We therefore implemented a novel systematic screening method with a simple predetermined questionnaire on infections and assessed its effectiveness. METHODS: We retrospectively reviewed medical records of individuals for whom intravenous bDMARDs were administered for RA from January 2016 to April 2019. We evaluated the performance of the new screening method based on physicians' assessments. In addition, a survey was administered to nurses, regarding their assessment of the usefulness of this new screening. The incidence of infections was also assessed. RESULTS: A total of 1636 cases underwent this new screening. The new screening method showed high sensitivity (0.97) and specificity (0.89) with a negative predictive value of 99.9%, as determined based on the physician's decision. Administration of bDMARDs was postponed in 37 (2.5%) patients, and there was only one case in which the screening failed to note an active infection. The nurses' survey demonstrated high agreement (87.5%) about the usefulness of this screening on the grounds of clarity, simplicity, ease, and time-saving effects. There was no significant increase in infections after implementation of this method. CONCLUSIONS: Systematic screening with a predetermined simple questionnaire is effective as an infection screening method, with a high negative predictive value. This approach contributes to high satisfaction of nurses and a time-efficient practice by focusing on screen-positive cases without increasing infections.
Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Productos Biológicos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/epidemiología , Infecciones Bacterianas/diagnóstico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVE: Patients with IgG4-related disease (IgG4RD) usually require steroid-sparing agents due to relapse with tapering glucocorticoids (GC). We aimed to determine the efficacy and safety of mizoribine (MZR) among IgG4RD patients. METHODS: We retrospectively reviewed records of IgG4RD patients at Immuno-Rheumatology Center in St. Luke's International Hospital, Tokyo, Japan. Patients treated with MZR were classified into the MZR group, and those treated with GC alone or with other immunosuppressants were included in the control group. Disease exacerbation, GC dose, IgG-IgG4 titre and adverse events were evaluated using univariate analyses, including the Kaplan-Meier method. The Cox proportional hazard model was used to evaluate risk factors for disease exacerbation. RESULTS: A total of 14 and 29 cases were included in the MZR and control group. Multiple organ involvement (three or more organs) was significantly more frequent in the MZR group [10 (71.4%) vs 9 (31.0%), P= 0.021]. Kaplan-Meier analysis revealed a significant reduction inexacerbation in patients with multiple organ involvement (P< 0.001) but not in total (P= 0.42). The adjusted hazard ratios of MZR use and multiple organ involvement for exacerbation were 0.34 (95%CI 0.12-1.01; P = 0.052) and 3.51 (95%CI 1.29-9.51; P= 0.014). The cumulative GC dose (mg per year, interquartile range) tended to be lower in the MZR group [1448 (1003-1642) vs 2179 (1264-3425); P= 0.09]. CONCLUSION: MZR decreased disease exacerbation among IgG4RD patients with multi-organ involvement and showed a steroid-sparing effect. MZR could be a treatment option for IgG4RD.
Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Ribonucleósidos/uso terapéutico , Biomarcadores/sangre , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulina G/sangre , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Belimumab is an effective and safe treatment option for systemic lupus erythematosus (SLE). However, data on treatment cessation are lacking. Thus, we investigated belimumab-free remission in SLE patients. SLE patients receiving belimumab in our institute (May 1, 2013-May 31, 2019) were retrospectively identified using electronic health records. Eligibility criteria included receiving belimumab for > 180 days and discontinuation for any reason. BILAG category A or B in at least one organ system indicated a disease flare. Follow-up monitoring during post-treatment at week 52 identified relapse-free and relapse patients. Thirty-one patients received belimumab, and 8 patients were included. Of the 8 patients, 4 relapsed within 52 weeks. At belimumab discontinuation, relapse-free patients achieved lower SELENA-SLEDAI (1 [IQR, 0-2] vs. 7 [IQR, 5.5-8] (p = 0.03)), received significantly less steroid (prednisolone equivalent, 3.0 mg/day [IQR, 2.8-3.2] vs. 9.5 mg/day [IQR, 7.3-13.3], p = 0.02) than relapse patients, and significantly more relapse-free patients achieved SELENA-SLEDAI less than 4 and received prednisolone less than 5 mg/day than relapse patients. Furthermore, on discontinuation day, relapse-free patients tended to have higher C3 (91.0 mg/dL [IQR, 78.8-102.3] vs. 56.0 mg/dL [IQR, 39.8-73.0], p = 0.15) and C4 levels (22.0 mg/dL [IQR, 19.00-26.00] vs. 11.0 mg/dL [IQR, 6.00-16.00], p = 0.08) and less anti-dsDNA antibody (5.2 IU/mL [IQR, 3.8-7.8] vs. 48.0 IU/mL [IQR, 11.5-137.3], p = 0.08) than relapse patients. Belimumab discontinuation can be considered for patients who achieved good responses. Normalization of complement, anti-dsDNA antibody, SELENA-SLEDAI less than 4, and steroid dosage less than 5 mg/day might be prognostic markers for belimumab-free remission.