Efficacy and tolerability of adalimumab (humira) in patients with active rheumatoid arthritis

Objective: to evaluate the efficacy and tolerability of adalimumab alone and in combination with basic anti-inflammatory drugs (BAIDs) in patients with rheumatoid arthritis (RA), by taking into account the specific features of the course of the disease. Subjects and methods. The study enrolled 30 patients with a verified diagnosis of RA, its high activity by DAS 28, and ineffective previous therapy with standard BAIDs. At the beginning of the study, 20 (66.7%) patients continued taking BAIDs. According to therapy, the patients were divided into 3 groups: 1) 10 (33.3%) patients received subcutaneous adalimumab injections only; 2) 12 (40%) took adalimumab+methotrexate (MT); 3) 8 (26.7%) had adalimumab+leflunomide. The patient groups were matched for age, the duration and activity of RA (by DAS 28), its X-ray stage and seropositivity. Nine (37.5%) patients took oral glucocorticoids (GCs) and 25 (83.3%) received non-steroidal anti-inflammatory drugs (NSAIDs). Two (8.3%) patients had previously been prescribed biological therapies. Adalimumab was subcutaneously injected every 2 weeks for 24 weeks. The quantitative parameters of articular syndrome and blood and urine biochemical and clinical analyses were used to evaluate therapeutic effectiveness. The effect of therapy was evaluated by the ACR and EULAR (DAS 28) criteria. The efficiency of therapy was evaluated 12 and 24 weeks after therapy. Results. The clinical and laboratory effect of adalimumab was noted in 29 (96.7%) of the 30 patients. All the assessed parameters of articular syndrome became significantly lower (p<0.001) by week 12 of therapy and to a greater extent by week 24. Evaluation of the efficiency of adalimumab therapy by the ACR criteria showed that following 12-week therapy, the parameters were decreased by 20% in 87% of the patients and 50% in 16.7%; after 24 weeks, 23.3, 70 and 96.7% achieved very good (ACR 70), good (ACR 50), and satisfactory (ACR 20) effects. Estimation of the time course of changes in the disease activity index (DAS 28) revealed that adalimumab significantly reduced disease activity. Therapeutic effectiveness was also shown as reduced needs for NSAIDs and GCs. Positive clinical and laboratory changes during adalimumab+ MT combination therapy were also demonstrated to be significantly higher than those during adalimumab monotherapy or adalimumab + leflunomide combination therapy. Conclusion. Adalimumab is an effective disease-modifying biological agent. Its benefits may include the rapid development (on days 4-5 on average) and long retention (for 6 months or more) of an effect, a good safety profile (adverse reactions occurred only in 16.7% of the patients), and easiness-to-use

Эффективность и переносимость адалимумаба (Хумира) у пациентов с активным ревматоидным артритом

Objective: to evaluate the efficacy and tolerability of adalimumab alone and in combination with basic anti-inflammatory drugs (BAIDs) in patients with rheumatoid arthritis (RA), by taking into account the specific features of the course of the disease. Subjects and methods. The study enrolled 30 patients with a verified diagnosis of RA, its high activity by DAS 28, and ineffective previous therapy with standard BAIDs. At the beginning of the study, 20 (66.7%) patients continued taking BAIDs. According to therapy, the patients were divided into 3 groups: 1) 10 (33.3%) patients received subcutaneous adalimumab injections only; 2) 12 (40%) took adalimumab+methotrexate (MT); 3) 8 (26.7%) had adalimumab+leflunomide. The patient groups were matched for age, the duration and activity of RA (by DAS 28), its X-ray stage and seropositivity. Nine (37.5%) patients took oral glucocorticoids (GCs) and 25 (83.3%) received non-steroidal anti-inflammatory drugs (NSAIDs). Two (8.3%) patients had previously been prescribed biological therapies. Adalimumab was subcutaneously injected every 2 weeks for 24 weeks. The quantitative parameters of articular syndrome and blood and urine biochemical and clinical analyses were used to evaluate therapeutic effectiveness. The effect of therapy was evaluated by the ACR and EULAR (DAS 28) criteria. The efficiency of therapy was evaluated 12 and 24 weeks after therapy. Results. The clinical and laboratory effect of adalimumab was noted in 29 (96.7%) of the 30 patients. All the assessed parameters of articular syndrome became significantly lower (p<0.001) by week 12 of therapy and to a greater extent by week 24. Evaluation of the efficiency of adalimumab therapy by the ACR criteria showed that following 12-week therapy, the parameters were decreased by 20% in 87% of the patients and 50% in 16.7%; after 24 weeks, 23.3, 70 and 96.7% achieved very good (ACR 70), good (ACR 50), and satisfactory (ACR 20) effects. Estimation of the time course of changes in the disease activity index (DAS 28) revealed that adalimumab significantly reduced disease activity. Therapeutic effectiveness was also shown as reduced needs for NSAIDs and GCs. Positive clinical and laboratory changes during adalimumab+ MT combination therapy were also demonstrated to be significantly higher than those during adalimumab monotherapy or adalimumab + leflunomide combination therapy. Conclusion. Adalimumab is an effective disease-modifying biological agent. Its benefits may include the rapid development (on days 4-5 on average) and long retention (for 6 months or more) of an effect, a good safety profile (adverse reactions occurred only in 16.7% of the patients), and easiness-to-use.Цель наблюдения - оценка эффективности и переносимости адалимумаба у больных РА как при монотерапии, так и в комбина- ции с базисными противовоспалительными препаратами (БПВП) с учетом особенностей течения заболевания. Материал и методы. В наблюдение было включено 30 больных с достоверным диагнозом РА и высокой активностью болезни по DAS 28 и неэффективностью предшествующей терапии стандартными БПВП. К моменту начала наблюдения продолжали принимать БПВП 20 (66,7%) пациентов. В соответствии с терапией пациенты были разделены на три группы: только подкожные инъекции адалимумаба по- лучали 10 (33,3%) больных, адалимумаб+метотрексат (МТ) - 12 (40%) и адалимумаб+лефлуномид - 8 (26,7%). Группы пациентов бы- ли сопоставимы по возрасту, длительности, активности РА (по DAS 28), его рентгенологической стадии и серопозитивности. Пероральные глюкокортикоиды (ГК) получали 9 (37,5%) больных, нестероидные противовоспалительные препараты (НПВП) - 25 (83,3%). Терапию биологическими агентами в прошлом назначали 2 (8,3%) пациентам. Адалимумаб вводили подкожно каждые 2 нед в течение 24 нед. Для оценки эффективности лечения использовали количественные параметры суставного синдрома, биохимические, клинические анализы крови и мочи. Эффект терапии оценивали по критериям ACR и EULAR (DAS 28). Оценку эффективности проводили через 12 и 24 нед терапии. Результаты. Клинико-лабораторный эффект адалимумаба отмечен у 29 (96,7%) из 30 больных. Все оцениваемые параметры сус- тавного синдрома достоверно (p<0,001) уменьшались к 12-й неделе и еще в большей степени - к 24-й неделе терапии. Оценка эф- фективности лечения адалимумабом по критериям ACR показала, что через 12 нед терапии уменьшение параметров на 20% от- мечалось у 87% больных, на 50% - у 16,7%; через 24 нед ответ на терапию зарегистрирован у 96,7% больных (ACR 20), 70% (ACR 50) и 23,3% (ACR 70). При оценке динамики индекса активности болезни (DAS 28) выявлено, что адалимумаб достоверно снижал активность заболева- ния. Эффективность терапии проявлялась также в снижении потребности в НПВП и ГК. Положительная динамика клинико-ла- бораторных показателей на фоне комбинированной терапии адалимумабом+МТ была достоверно выше, чем при монотерапии ада- лимумабом или использовании комбинации адалимумаб + лефлуномид. Заключение. Адалимумаб - эффективный болезнь-модифицирующий биологический препарат. К его преимуществам можно отне- сти быстрое развитие (в среднем на 4-5-й день) и длительное сохранение (6 мес и более) эффекта, хороший профиль безопасности (побочные явления возникли лишь у 16,7 больных), удобство введения

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome.Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.Transplantation and immunomodulatio