Early Therapy

About: Early Therapy is a research topic. Over the lifetime, 317 publications have been published within this topic receiving 8833 citations.

Diagnosis and Management of Rheumatoid Arthritis: A Review.

Abstract: Importance Rheumatoid arthritis (RA) occurs in about 5 per 1000 people and can lead to severe joint damage and disability. Significant progress has been made over the past 2 decades regarding understanding of disease pathophysiology, optimal outcome measures, and effective treatment strategies, including the recognition of the importance of diagnosing and treating RA early. Observations Early diagnosis and treatment of RA can avert or substantially slow progression of joint damage in up to 90% of patients, thereby preventing irreversible disability. The development of novel instruments to measure disease activity and identify the presence or absence of remission have facilitated new treatment strategies to arrest RA before joints are damaged irreversibly. Outcomes have been improved by recognizing the benefits of early diagnosis and early therapy with disease-modifying antirheumatic drugs (DMARDs). The treatment target is remission or a state of at least low disease activity, which should be attained within 6 months. Methotrexate is first-line therapy and should be prescribed at an optimal dose of 25 mg weekly and in combination with glucocorticoids; 40% to 50% of patients reach remission or at least low disease activity with this regimen. If this treatment fails, sequential application of targeted therapies, such as biologic agents (eg, tumor necrosis factor [TNF] inhibitors) or Janus kinase inhibitors in combination with methotrexate, have allowed up to 75% of these patients to reach the treatment target over time. New therapies have been developed in response to new pathogenetic findings. The costs of some therapies are considerable, but these costs are decreasing with the advent of biosimilar drugs (drugs essentially identical to the original biologic drugs but usually available at lower cost). Conclusions and relevance Scientific advances have improved therapies that prevent progression of irreversible joint damage in up to 90% of patients with RA. Early treatment with methotrexate plus glucocorticoids and subsequently with other DMARDs, such as inhibitors of TNF, IL-6, or Janus kinases, improves outcomes and prevents RA-related disability. A treat-to-target strategy aimed at reducing disease activity by at least 50% within 3 months and achieving remission or low disease activity within 6 months, with sequential drug treatment if needed, can prevent RA-related disability.

Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis

Abstract: Objective. Delay of disease-modifying anti-rheumatic drug (DMARD) therapy is a major contributing factor for poor outcome in rheumatoid arthritis (RA). Although early therapy has been shown to be particularly effective, there is still uncertainty about the optimal time point of DMARD introduction. We wanted to test if a therapeutic window of opportunity may exist within the first few months of the disease. Methods. In this case-control parallel-group study, 20 very early RA (VERA) patients with median disease duration of 3 months were age and gender matched to a group of 20 late early RA (LERA) patients with median disease duration of 12 months until first DMARD initiation. Follow-up time was 36 months. Primary outcome measures were the disease activity score (DAS28) and radiological joint destruction using the Larsen method. Results. Already after 3 months of DMARD therapy we found a significant difference of improvement in favour of the VERA patients in the DAS28. This trend continued over the study period. At study end the DAS28 showed an improvement of 2.8±1.5 in the VERA vs 1.7±1.2 in the LERA group (P c < 0.05). The Larsen scores showed a statistically significant retardation of progression in the VERA compared with the LERA. Conclusion. Our results indicate that there is a window of opportunity for highly successful treatment of RA in the first year, and especially within the first 3 months of therapy. Thus, early diagnosis and therapy may be the crucial step in achieving optimal control of disease progression and prognosis in RA.

Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders

Abstract: AIMS To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). METHODS Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. RESULTS Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 × 10 9 /l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. CONCLUSION MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential. Key messages MAS is a rare complication of childhood rheumatic disease It is a potentially fulminant disorder, which may occur as part of the initial presentation of the rheumatic disease An infective trigger may herald the onset of this complication in predisposed patients Differentiation from a disease flare may be difficult, but is critical to ensure optimal outcome An early and dramatic fall in platelet count is characteristic, with changes in WBC and haemoglobin being more variable early and common Elevation in transaminases and coagulation abnormalities may not be present at onset of MAS Bone marrow examination is supportive, but false negative reports occur as a result of sampling errors or the subtle nature of the disease Multisystem involvement is a poor prognostic sign

Neuromyelitis optica: Clinical predictors of a relapsing course and survival

Abstract: Background: The relapsing form of neuromyelitis optica (NMO) is characterized by recurrent optic neuritis and myelitis, usually leading to severe, permanent, relapse-related neurologic impairment (e.g., blindness, paraplegia) within 5 years. Aggressive therapy aimed at relapse prevention initiated soon after disease onset may be expected to have a relatively greater impact on early relapse-related disability in NMO than in typical MS. Early prediction of a relapsing course and subsequent disease severity would facilitate design and implementation of clinical trials of such therapies. Methods: A database of clinical and laboratory features of patients with NMO (n = 80) was used to develop potentially useful models predictive of a relapsing disease course and of subsequent disease severity as measured by survival. Results: Predictors of a relapsing course were longer interattack interval between the first two clinical events (rate ratio [RR] = 2.16; per month increase), older age at onset (RR = 1.08; per year increase), female sex (RR = 10.0, female vs male), and less severe motor impairment with the sentinel myelitis event (RR = 0.48; per severity scale point increase). A history of other autoimmune disease (RR = 4.15; presence vs absence), higher attack frequency during the first 2 years of disease (RR = 1.21; per attack), and better motor recovery following the index myelitis event (RR = 1.84; per point increase) were associated with mortality due to relapsing NMO. Conclusions: These predictive models identify several clinical features, each available at diagnosis or early in the disease course, that predict relapsing disease and survival. These results may be useful to identify patients at high risk for severe, relapsing neuromyelitis optica in order to initiate early therapy for relapse prevention and to design clinical trials to study such interventions.

Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer : A new noninvasive predictive assay

Abstract: Purpose: This study investigated sequential changes in tumor blood supply using magnetic resonance (MR) perfusion imaging and assessed their significance in the prediction of outcome of patients with advanced cervical cancer The purpose of this project was to devise a simple, noninvasive method to predict early signs of treatment failure in advanced cervical cancer treated with conventional radiation therapy Methods and Materials: Sixty-eight MR perfusion studies were performed prospectively in 17 patients with squamous carcinomas (14) and adenocarcinomas (3) of the cervix, Stages bulky IB (1), IIB (5), IIIA (1), IIIB (8), and IVA (1), and recurrent (1) Four sequential studies were obtained in each patient: immediately before radiation therapy (pretherapy), after a dose of 20–22 Gy/∼2 weeks (early therapy), after a dose of 40–45 Gy/∼4–5 weeks (midtherapy), and 4–6 weeks after completion of therapy (follow-up) Perfusion imaging of the tumor was obtained at 3-s intervals in the sagittal plane A bolus of 01 mmol/kg of MR contrast material (gadoteridol) was injected intravenously 30 s after beginning image acquisition at a rate of 9 ml/s using a power injector Time/signal-intensity curves to reflect the onset, slope, and relative signal intensity (rSI) of contrast enhancement in the tumor region were generated Median follow-up was 8 months (range 3–18 months) Results: Tumors with a higher tissue perfusion (rSI ≥ 28) in the pretherapy and early therapy (20–22 Gy) studies had a lower incidence of local recurrence than those with a rSI of p = 005) An increase in tumor perfusion early during therapy (20–22 Gy), particularly to an rSI of ≥ 28, was the strongest predictor of local recurrence (0% vs 78%; p = 0002) However, pelvic examination during early therapy (20–22 Gy) commonly showed no appreciable tumor regression The slope of the time/signal-intensity curve obtained before and during radiation therapy also correlated with local recurrence Follow-up perfusion studies did not provide information to predict recurrence Conclusion: These preliminary results suggest that two simple MR perfusion studies before and early in therapy can offer important information on treatment outcome within the first 2 weeks of radiation therapy before response is evident by clinical examination Highg tumor perfusion before therapy and increasing or persistent high perfusion early during the course of therapy appear to be favorable signs High perfusion suggests a high blood and oxygen supply to the tumor The increase in tumor perfusion seen in some patients early during radiation therapy suggests improved oxygenation of previously hypoxic cells following early cell kill Radiation tehrapy is more effective in eradicating these tumors, resulting in improved local control Our technique may be helpful in identifying early —while more aggressive therapy can still be implemented—those patients who respond poorly to conventional radiation therapy