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[Clinical relapse of rheumatoid arthritis (escape phenomenon) during low-dose methotrexate therapy].

OBJECTIVE: To clarify the incidence and background of clinical relapse (escape phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis. METHODS: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30, 1995. Among them, 60 patients showed clinical improvement within 6 months after the start of the therapy and were subjected to the analysis for clinical relapse (escape phenomenon). RESULTS: Twelve patients showed an initial improvement followed by a relapse with increased serum CRP and number of painful joints despite the MTX therapy was continued. Two types of the relapses were seen; (1) early, escape (relapse after an initial brief improvement) in 7 patients, and (2) late escape (relapse after a long-term improvement with MTX therapy) in 5 patients. The early escape was seen at 9.0 +/- 0.7 months after the start of therapy while the late escape was seen at 23.3 +/- 4.8 months. Patients with both types of escape phenomenon had the longer duration of the disease and more advanced stage. There was no relationship between clinical relapse and age, baseline RA activity, MTX dose, or concurrent use of corticosteroids and other disease modifying anti-rheumatic drugs. The efficacy of MTX for RA was restored by increasing dose of MTX in 11 patients. CONCLUSION: These results suggest that clinical relapse is not rare in RA patients during low-dose methotrexate therapy, but could be improved by increasing dose.

Antirheumatic Agents↗

Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis.

Immunization of (PL/J x SJL/J)F1 mice with myelin basic protein (MBP) induces relapsing experimental autoimmune encephalomyelitis (EAE). Relapses occur 7 to 10 days after recovery from the initial paralysis. Staphylococcal enterotoxins (SE) A or B, administered after recovery from the initial paralysis, induce immediate relapses. IL-12 is involved in the induction of EAE. Here, we show that SEA and SEB induce IL-12 in splenocytes from (PL/J x SJL/J)F1 mice in vitro and increase the level of IL-12 in the sera of mice treated with these superantigens. IL-12 administration mimics SE in inducing spontaneous relapses and in enhancing the severity and frequency of spontaneous relapses. IL-12 neutralization blocks SE-induced and subsequent relapses of EAE, and, when instituted after recovery from the initial attack, prevents spontaneous relapse. This is the first report of prevention of relapses of EAE with anti-IL-12 Ab, an approach which may prove useful in the prevention of exacerbations in multiple sclerosis.

Animals↗

The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients-- twenty-four months follow-up.

The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN beta therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti-inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN beta therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN beta and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to 2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).

Adjuvants, Immunologic↗

Detection of relapsing fever in human blood samples from Israel using PCR targeting the glycerophosphodiester phosphodiesterase (GlpQ) gene.

Relapsing fever caused by Borrelia persica is an acute tick-borne disease infecting people in the Middle East. A PCR test targeting the glycerophosphodiester phosphodiesterase (GlpQ) gene was used to detect infection in the blood of suspected relapsing fever patients. The assay detected infection in all 19 patients from Israel who were spirochetemic by blood smear examination and in two additional patients with clinical relapsing fever who were negative by smear examination. Patients were positive by PCR of blood only at the febrile stage and not during the incubation period prior to the appearance of clinical symptoms. Of 52 tick-bitten subjects who were tested and followed-up after being bitten by ticks, 10 developed symptoms of relapsing fever and all became positive by PCR following an earlier negative test. Partial sequencing of the 16S rRNA gene supported by phylogenetic analysis indicated that infection was caused by B. persica or a closely related species. A phylogenetic analysis of the GlpQ sequence showed that it was different yet closely related to other relapsing fever Borrelia spp. present in the Old World. The GlpQ PCR was positive also with the relapsing fever spirochetes B. recurrentis and B. crocidure but not with the Lyme disease agent B. burgdorferi DNA. A second modified GlpQ PCR was able to discriminate between probable B. persica and B. recurrentis and B. crocidurae infection. This study describes the first molecular assay for the diagnosis of relapsing fever caused by B. persica.

Borrelia↗

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis.

Intravenous immunoglobulin (IVIG) has several effects on the immune system that could have a beneficial influence on disease processes in multiple sclerosis (MS). Four double-blind trials in relapsing-remitting MS have demonstrated that IVIG may reduce the relapse rate, progression and the number of gadolinium-enhancing lesions. However, these trials were smaller than the pivotal trials of interferon-beta and glatiramer acetate, and therefore, we performed a meta-analysis of the four trials in order to provide an overall assessment of the benefits of IVIG in relapsing-remitting multiple sclerosis in comparison with other drugs currently available for treatment of disease activity in MS. The meta-analysis showed a significant beneficial effect on the annual relapse rate (effect size -0.5; P = 0.00003), on the proportion of relapse-free patients (0.29 difference; P = 2.1 x 10(-8)), change in Expanded Disability Status Scale (EDSS) score (effect size: 0.25; P = 0.04), and a trend towards a reduction in the proportion of patients who deteriorated (P = 0.03). Each single study in the meta-analysis had its weaknesses, but all studies were positive regarding their primary end-point, and the results yield concordant evidence for reduction of relapse rate and progression. The ideal dosage of IVIG for treating MS needs still to be determined. In conclusion, IVIG may be a valuable alternative for treatment of relapsing-remitting MS, but can presently not be considered as a first-line treatment. IVIG could be considered in patients who do not tolerate or are unwilling to take the approved injectable medications, but additional studies are needed to establish the role of IVIG in the management of multiple sclerosis.

Persons with Disabilities↗

Neurotrophic factors and clinical recovery in relapsing-remitting multiple sclerosis.

Pathogenic autoimmune cells are demonstrated to be able to produce neurotrophic factors during acute phase of multiple sclerosis (MS). In this study, we determined the production of various neurotrophins [brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4)] and some pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] by unstimulated peripheral blood mononuclear cells (PBMC) in 21 relapsing-remitting MS patients during different phases of disease (stable, relapse and post-relapse). During acute phase of disease, we detected a considerable increase of BDNF, TNF-alpha and IFN-gamma production, while significantly higher levels of GDNF, NGF, NT3 and NT4 were found in post-relapse phase. When neurotrophin production was correlated with clinical outcome (complete or partial recovery from new symptoms), we found a significantly higher BDNF production in relapse phase followed by increased GDNF, NGF, NT3 and NT4 levels during post-relapse phase in subjects with complete remission only. During relapse phase, we detected a significant increase of pro-inflammatory cytokines, that was more evident in patients with partial recovery. The neuroprotective potential of immune cells seems to be inversely correlated with disease duration and with the age of patients.

Adult↗

A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients.

BACKGROUND: Interferon beta 1b (Betaferon) and 1a (Avonex) were licensed in Italy for treating relapsing-remitting multiple sclerosis in February 1996 and August 1997, respectively. OBJECTIVES: To evaluate the effectiveness of these agents on the basis of clinical experience in northern Italian multiple sclerosis centres. DESIGN: Clinical data on patients with relapsing-remitting multiple sclerosis were collected on an appropriate form from 65 centres in northern Italy. Intention to treat analysis was not possible, so patients who discontinued treatment (drop-outs) and who continued treatment (treated) were analysed separately. The main outcome measures were annual relapse frequency, number of relapse-free patients, mean change in extended disability status scale score (EDSS), and number of patients who worsened. RESULTS: 1481 patients were included; 834 were treated with Betaferon and 647 with Avonex for mean periods of 21.4 and 12.0 months, respectively. Basal EDSS was 2.37 and 2.17, respectively, and relapse frequency was 1.62 and 1.45. The annual relapse rate decreased by more than 60% with Betaferon and 55% with Avonex. The proportions of relapse-free, improved, and worsened patients were similar in the two groups. More patients interrupted treatment with Betaferon (41.1%) than with Avonex (15.3%); such patients showed more active disease at baseline and during treatment. The incidence of side effects was higher in Betaferon treated patients. CONCLUSIONS: The effectiveness of Betaferon and Avonex is confirmed. There was a more marked effect than expected from the experimental trial results. This might reflect differences in inclusion criteria, or, more likely, loss of drop-outs, favouring selective retention of responders.

Adjuvants, Immunologic↗

Day&#x2009;+&#x2009;30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved outcomes in patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15-35% of these patients after transplantation. Therefore, early and highly sensitive detection methods are required to identify patients at risk of relapse and enable timely post-transplant intervention. METHODS: In this NICHE cohort study, a total of 136 patients were included, then we evaluated whether high-sensitivity polymerase chain reaction (PCR)-next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 5&#x2009;&#xd7;&#x2009;10-6) on day&#x2009;+&#x2009;30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy. RESULTS: Among the 136 patients, 37 patients (27.2%) had detectable FLT3-ITD clones on day&#x2009;+&#x2009;30. These patients exhibited a significantly higher cumulative incidence of post-HSCT multiparameter flow cytometry (MFC)-measurable residual disease (MRD) relapse (40.3% vs. 18.8%, p&#x2009;=&#x2009;0.001). Notably, FLT3-ITD-positive patients who received FLT3 inhibitor maintenance therapy had no relapses, while 6 out of the 13 patients who did not receive maintenance therapy relapsed. Conversely, FLT3-ITD-negative patients without high-risk factors (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MFC-MRD positivity pre-HSCT) showed limited benefit from maintenance therapy (MFC-MRD-free survival: hazard ratio (HR)&#x2009;=&#x2009;0.25 (0.03-2.11), p&#x2009;=&#x2009;0.204; OS: HR&#x2009;=&#x2009;0.20 (0.02-1.70), p&#x2009;=&#x2009;0.142). CONCLUSIONS: This is the first study to demonstrate that detection of minimal FLT3-ITD clones at the fixed time point of day&#x2009;+&#x2009;30 post-HSCT can reliably stratify relapse risk in AML patients and provide a rationale for individualized post-transplant maintenance therapy.

Humans↗

Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria.

We assessed the proportion and potential predictors of response to interferon-beta (IFNbeta) therapy in relapsing remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNbeta-1b subcutaneously (SC) (Betaferon), 59 IFNbeta-1a intramuscularly (Avonex) and 55 IFNbeta-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

Adjuvants, Immunologic↗

Clinical characteristics of responders to interferon therapy for relapsing MS.

OBJECTIVE: To determine the proportion of patients with multiple sclerosis (MS) who respond to interferon-beta (IFNB) therapy and assess whether clinical characteristics differ in IFNB responders vs nonresponders. METHODS: Data on all patients who received IFNB who were entered in the prospective European Database for Multiple Sclerosis (EDMUS) database in Lyon as of March 31, 2001, were reviewed. Responders were defined as having a lower relapse rate on IFNB compared with the year or 2 years prior to IFNB therapy. RESULTS: Two hundred sixty-two patients with relapsing MS received at least 6 months of IFNB: 200 relapsing remitting (RR) and 62 relapsing secondary progressive (SP). One-third of patients experienced a higher or identical annual relapse rate while on IFNB treatment. Compared with nonresponders, responders were older and had longer disease duration at the time IFNB was initiated. RRMS responders also had a higher relapse rate during the year prior to IFNB therapy and SPMS responders had a higher Disability Status Scale score at initiation of IFNB. CONCLUSION: Clinical profiles of patients with relapsing MS who respond to IFNB may differ from those who do not with a more inflammatory and less neurodegenerative disease at the time IFNB is initiated.

Adult↗

A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.

BACKGROUND: Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II study, the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis (MS) with relapses. METHODS: Patients (n = 179) with relapsing-remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day for 36 weeks. MRI brain scans were performed every 6 weeks. The primary endpoint was the number of combined unique active lesions per MRI scan. Secondary endpoints included MRI-defined disease burden, relapse frequency, and disability increase. RESULTS: The median number of combined unique active lesions per scan was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p < 0.03 vs placebo), and teriflunomide 14 mg/day (p < 0.01 vs placebo) groups during the 36-week double-blind treatment phase. Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden. Teriflunomide treatment resulted in trends toward a lower annualized relapse rate and fewer relapsing patients (14 mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase. Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups. CONCLUSION: Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.

Adult↗

A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate whether the efficacy of interferon-beta (IFNbeta) treatment of relapsing-remitting MS (RR-MS) was influenced by type, dose, and frequency of administration. METHODS: From June 1996 through October 1997, the authors offered participation to all Danish RR-MS patients who met the following criteria: definite MS, at least two relapses within 2 years, age 18 to 55, and an Expanded Disability Status Scale (EDSS) score of < or = 5.5. The study was multicenter, controlled, open-label, randomized, head-to-head comparing IFNbeta-1a 22 microg once a week (n = 143) with IFNbeta-1b 250 microg every other day (n = 158), both subcutaneously, for 24 months. Patients who declined randomization were offered treatment with IFNbeta-1b 250 microg every other day (n = 120). The primary end-points were the annualized relapse rate, the time to first relapse, and neutralizing antibody formation. The secondary endpoint was time to sustained progression. RESULTS: The annual relapse rates were virtually equal in the two arms of the randomized study (IFNbeta-1a: 0.70; IFNbeta-1b: 0.71); so were the time to first relapse and the time to sustained progression. In the nonrandomized patients (IFNbeta-1b), the annual relapse rate was not significantly different, but the time to progression was shorter. CONCLUSION: In this study, 250 microg interferon-beta-1b administered every other day did not prove clinically superior to once-a-week administration of 22 microg interferon-beta-1a.

Adjuvants, Immunologic↗

Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS.

BACKGROUND: IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy. OBJECTIVE: To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS. METHODS: The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months. RESULTS: Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years. CONCLUSIONS: In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.

Adolescent↗

Evidence for additional genetic risk indicators of relapse-onset MS within the HLA region.

BACKGROUND: Human leukocyte antigen (HLA)-DR2 carriership is associated with an increased risk for MS. Genome searches using microsatellite markers have consistently shown that additional genetic factors contribute to susceptibility for MS. OBJECTIVE: To identify loci within the HLA region that predispose to relapse-onset MS independently of HLA-DR2. METHOD: A case-control study involving 159 patients with definite relapse-onset MS and 273 control subjects was conducted. Six highly polymorphic microsatellite markers encoded within the HLA-C to DR region, that is, D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2, three single-nucleotide tumor necrosis factor (TNF) promoter gene polymorphisms at positions -238, -308, and -376, and HLA-DR2 carriership were typed. RESULTS: These data confirmed the well-known association between the HLA-DR2 haplotype and relapse-onset MS, yielding an odds ratio (OR) of 3.6 (95% CI: 2.4 to 5.4; p < 0.0001). Multivariate analyses revealed that C1_3_2*354 was also associated with an increased risk for developing relapse-onset MS independently of HLA-DR2 (OR: 2.0; 95% CI: 1.2 to 3.1; p = 0.004). This allele is encoded within an ancestral haplotype that is highly linked to HLA-DR3. The joint effect of this ancestral haplotype and HLA-DR2 resulted in an OR of 8.7 (95% CI: 2.7 to 29; p < 0.0001) to develop relapse-onset MS. In addition, a protective risk factor was found: carriers of TNFa*107 had a 0.5-fold lower risk to develop relapse-onset MS (95% CI: 0.3 to 0.9; p = 0.026). CONCLUSION: Within the HLA region, other loci besides HLA-DR2 haplotype modulate susceptibility for relapse-onset MS.

Adult↗

Management of patients who have relapses in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological condition, which disrupts the typical functions and daily activities of those affected. Approximately 80% of those diagnosed will follow a relapsing/remitting disease course at diagnosis. Patients with relapsing/remitting MS can expect to have episodes of relapse or an exacerbation of the disease and its variety of symptoms. Management of such episodes has always been open to the preferences of the healthcare professionals involved. The aim of this article is to review the evidence that exists to support current practice in the management of patients during a relapse and to evaluate how this evidence can be incorporated into patient care. The article begins by giving an overview of MS, and continues by determining what a relapse is and discussing the speculated triggers of relapse. Methods of treating relapse are then explored. It concludes by highlighting the strongest evidence-based method for treating relapses, and by emphasizing the need for further research into the pharmaceutical and non-pharmaceutical management of MS relapses.

Adrenal Cortex Hormones↗

Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride.

The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy (ST). A total of 105 patients were randomly assigned to the various treatments and maintained under controlled conditions for two years or until relapse. Relapse rates for all treatments remained traditionally high. Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year, indicating that drug noncompliance does not adequately explain early schizophrenic relapse. However, patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time. Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers, yet both groups were diagnostically and symptomatically equivalent prior to treatment. Personal discomfort and intrafamilial stress are important predictors.

Administration, Oral↗

A program for relapse prevention in schizophrenia: a controlled study.

BACKGROUND: This study examined whether a program for relapse prevention (PRP) is more effective than treatment as usual (TAU) in reducing relapse and rehospitalization rates among outpatients with schizophrenia. METHODS: Eighty-two outpatients with DSM-III-R schizophrenia or schizoaffective disorder were randomly assigned to receive either PRP (experimental group, n = 41) or TAU (control group, n = 41) and were followed up for an 18-month prospective controlled study. Patients in both groups were prescribed standard doses of maintenance antipsychotic medication. Treatment with PRP consisted of a combination of psychoeducation, active monitoring for prodromal symptoms with clinical intervention when such symptoms occurred, weekly group therapy for patients, and multifamily groups. The TAU consisted of biweekly individual supportive therapy and medication management. RESULTS: Outcome rates over 18 months were 17% for relapse (7 patients) and 22% for rehospitalization (9 patients) in the PRP group, compared with 34% for relapse (14 patients) and 39% for rehospitalization (16 patients) in the TAU group (P = .01 and P = .03, respectively). Addition of age, sex, baseline Global Assessment Scale score, Positive and Negative Syndrome Scale scores (3 measures), and substance abuse to the proportional hazards regression models all yielded nonsignificant effects. The PRP teams were much more likely than the TAU psychiatrists to identify prodromal episodes before patients met objective relapse criteria or needed hospitalization. CONCLUSIONS: The PRP was effective in detecting prodromal symptoms of relapse early in an episode. Crisis intervention including increased antipsychotic medication use during the prodromal phase reduced relapse and rehospitalization rates.

Adult↗