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Results for “disease-modifying therapy”

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PubMed2026

In vivo epigenome editing reduces circulating lipids and attenuates atherosclerosis in mice.

Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE-/- mice, CRISPRoff mediates robust and durable repression of these targets, leading to marked reductions in circulating total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In the ApoE-/- context, epigenetic silencing of Pcsk9 confers pronounced vascular protection, including decreased lipid accumulation in the liver and aortic root, reduced necrotic core formation, diminished macrophage infiltration, and enhanced plaque stability. Together, these results provide proof of principle that CRISPRoff-based epigenome editing enables stable repression of clinically relevant targets and ameliorates key features of atherosclerotic disease. This work lays the foundation for broader therapeutic applications of epigenetic modulation in cardiovascular disorders.

Animals↗

PubMed1991

Disease-modifying antirheumatic drugs: gold, penicillamine, antimalarials, and sulfasalazine.

In the assessment of the effects of disease-modifying antirheumatic drugs, three or four clinical measurements supported by the erythrocyte sedimentation rate, and sometimes radiographs, are generally agreed to be correct. Some advocate functional assessments also, or even alternatively. Several studies compared gold, penicillamine, antimalarials, and sulfasalazine either with each other or with placebo, and occasionally with methotrexate. No important differences between the general performance of the four drugs were found. More work was reported on sulfasalazine than on the other three drugs; the data support that it has a place in our armamentarium. Several important contributions concerned strategies of treatment. It is considered that disease-modifying antirheumatic drugs should be used earlier and more aggressively in rheumatoid arthritis. This aspect was perhaps the key note of the 1990 literature on this topic. As part of the new strategies, combination therapy is urged by some rheumatologists, whereas others urge caution on the grounds that we do not yet know enough about the effects of combinations, or by how much the risks of adverse effects are increased in combination.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

20 years' experience with ketoprofen.

Ketoprofen has emerged as a potent nonsteroidal anti-inflammatory drug. Its efficacy in the treatment of conditions such as rheumatoid arthritis and osteoarthritis has been demonstrated throughout nearly 20 years of clinical use. It has also been shown to be an effective analgesic. In comparative studies, ketoprofen appears to be at least as effective as other anti-inflammatory and analgesic agents. Because of its short half-life (approximately 1.5 hours) no dosage adjustment appears to be necessary in elderly patients unless there is concomitant renal insufficiency. Although rapidly eliminated from plasma, elimination from synovial fluid is delayed, so therapeutic concentrations can be maintained in affected joints without necessitating frequent administration. The side effects of ketoprofen are similar to those of all NSAIDs, gastrointestinal disturbances being the most frequent. Evidence for the adverse effects of NSAIDs on cartilage is still limited. Drug interactions are similar to those of all NSAIDs, antacids, methotrexate and probenecid being particularly important. Ketoprofen is available in a wide range of formulations, each designed to provide appropriate therapy in specific clinical situations: oral capsules for short term therapy; sustained release forms for chronic therapy and once-daily administration; suppositories to avoid possible gastrointestinal disturbances in susceptible patients; intramuscular preparations for rapid action; and a gel formulation for topical treatment. In the future, research should determine whether ketoprofen and other NSAIDs have any disease-modifying effects on inflammatory conditions in addition to providing symptomatic relief.

Animals↗

PubMed1992

Treatment strategies in rheumatoid arthritis.

Intervention therapies in rheumatoid arthritis (RA) are directed at the immune dysregulation and chronic inflammatory events in the joint. An ideal therapeutic program would rapidly control inflammation, prevent joint damage and preserve function. The various strategies of treatment involve the use of disease-modifying anti-rheumatic agents (DMARDs) either singly or in combination. Gold salts, penicillamine, sulphasalazine, methotrexate and hydroxychloroquine are used when NSAIDs fail to control inflammation. RA not only decreases the functional disability but the life-span of patients. The traditional pyramid strategy which uses single DMARDs consecutively has been found to be inadequate and slow in suppressing joint inflammation. Hence the race to find treatment regimes and strategies that will favourably alter the outcome of RA patients. Both the "step-down bridge" approach and saw-tooth strategy have been advocated in the attempt to break the progression of joint disease. None of the known regimes can be said to be most beneficial and least toxic.

Arthritis, Rheumatoid↗

PubMed2026

Precision Medicine in Transfusion-Dependent and Non-Transfusion-Dependent β-Thalassemia: Toward Personalized Diagnosis and Therapy.

β-thalassemia comprises a clinically heterogeneous group of disorders in which anemia severity, transfusion exposure, iron loading, and organ complications vary widely among individuals. This structured narrative review summarizes practical applications of precision medicine in transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT), with explicit attention to which strategies apply to each clinical category. Literature indexed in PubMed and Scopus from 2000 to 2025 was reviewed using terms related to thalassemia, precision medicine, magnetic resonance imaging (MRI), chelation tailoring, next-generation sequencing (NGS), fetal hemoglobin (HbF) modifiers, luspatercept, mitapivat, hepcidin, gene therapy, gene editing, and artificial intelligence (AI). Evidence was synthesized descriptively because interventions, outcomes, and populations were heterogeneous, and no pooled meta-analysis was performed. In TDT, precision care is centered on individualized transfusion planning, extended red-cell antigen matching, MRI-guided cardiac and hepatic iron monitoring, organ-directed chelation intensification, and selection of disease-modifying or curative approaches. In NTDT, precision care emphasizes accurate phenotype classification, MRI liver iron concentration, because serum ferritin may underestimate iron burden, selective chelation, surveillance for NTDT-specific complications, and individualized use of agents that improve anemia. Personalized chelation should include deferiprone, either alone or in combination, when cardiac iron is increased. Comprehensive molecular diagnosis should include HBB together with HBA1 and HBA2 assessment, while secondary and tertiary modifiers help explain phenotypic variability and complication risk. Hepcidin and growth differentiation factor 15 (GDF-15) are discussed as investigational biomarkers; transferrin saturation is not recommended for routine iron-overload assessment in thalassemia. AI currently has its strongest role in screening and diagnosis, whereas risk-stratification models remain exploratory. Equitable implementation requires standardized TDT/NTDT pathways, regional MRI and genomics access, longitudinal registries, and multidisciplinary interpretation.

Humans↗

PubMed1992

[Therapeutic maintenance and tolerance of sulfasalazine in rheumatoid polyarthritis. Retrospective study of 95 patients].

This retrospective study evaluated treatment with sulfasalazine (SAS) in a mean dosage of 2.1 g/day in 95 patients with rheumatoid arthritis (RA) who were followed-up for 3 months to 4 years. Mean disease duration was 7 years; 79 patients had previously received at least one disease-modifying drug. Four per cent of patients were lost to follow-up. Mean duration of treatment was 15 months (3 weeks-50 months). Treatment continuation rates were 57% at one year, 40% at two years, and 26% at three years. Reasons for discontinuation of SAS included adverse effects (n = 24), inefficacy (n = 33), and death unrelated to SAS therapy (n = 2). In four patients, SAS was discontinued within three months of the first dose because of a severe adverse effect (diffuse erythematous rash, diffuse bullous rash, hepatitis with jaundice, agranulocytosis). SAS-induced biologic markers for lupus were seen in one patient. Furthermore, 12% of evaluable patients developed antinuclear antibodies during SAS therapy. The SAS treatment continuation rate was higher (p = 0.05) among patients under 40 years of age (n = 18) than among older patients. This difference was due to a correlation between age and tolerance with less SAS-induced side effects in patients under 40 years of age (p = 0.03). The SAS treatment continuation rate was unrelated to the duration of rheumatoid arthritis or number of previous maintenance treatments. This study suggests that rheumatoid arthritis patients under 40 years of age exhibit better tolerance to SAS therapy.

Adolescent↗

PubMed1991

Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy.

Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti-IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti-IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease-modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic antirheumatic therapy on mast cells isolated from synovium of patients with arthritis.

Adult↗

PubMed1992

Treatment of rheumatoid arthritis with single dose or weekly pulses of chimaeric anti-CD4 monoclonal antibody.

The aetiology of rheumatoid arthritis is unknown but CD4+ T cells are known to be involved in its pathogenesis. Because of this, anti-CD4 monoclonal antibody has been used in open studies with clinical benefit in up to 60% of patients. We have used a chimaeric anti-CD4 monoclonal antibody (cM-T412, Centocor) in a randomized, double-blinded, placebo controlled trial as treatment for rheumatoid arthritis. Nine patients with active rheumatoid arthritis resistant to traditional disease-modifying drugs were recruited. Four received an intravenous 50 mg bolus of antibody, and three received 50 mg weekly for four consecutive weeks. Two patients received placebo. Despite a marked reduction (P less than 0.001) in peripheral blood CD4+ lymphocytes, there was no significant clinical improvement in any of these patients. The decrease in CD4+ lymphocyte number lasted one week after a single 50 mg dose of cM-T412 but was more prolonged in the patients who received four infusions. CD8+ T cells, CD16+ cytotoxic cells and CD14+ monocytes showed only a transient reduction. It may be concluded that the therapeutic efficacy of anti-CD4 therapy is not directly related to CD4+ T-cell lymphopenia.

Adult↗

PubMed2024

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Animals↗

PubMed2026

Duchenne muscular dystrophy: from gene to gene-ius therapies.

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional dystrophin, leading to progressive muscle degeneration, loss of ambulation, respiratory failure, cardiomyopathy, and premature mortality. Despite advances in multidisciplinary supportive care, DMD remains an incurable disease associated with substantial physical, psychosocial, and economic burdens. The monogenic nature of DMD and its well-defined molecular pathogenesis have made it a prime target for the development of precision therapies aimed at restoring dystrophin expression or modifying disease progression. This review provides an overview of the genetic and molecular mechanisms underlying DMD, summarizes its clinical manifestations and natural history, and discusses current standards of care. It further examines recent advances in disease-modifying therapeutic strategies, including exon-skipping antisense oligonucleotides, nonsense mutation readthrough agents, adeno-associated virus (AAV)-mediated micro-dystrophin gene replacement, and emerging genome-editing technologies such as CRISPR/Cas9. The review also highlights the limitations of existing treatments, including mutation specificity, variable efficacy, immune-related challenges, and uncertainties regarding long-term durability and safety. Finally, it considers future directions in therapeutic development, emphasizing the need for combination approaches, improved delivery systems, and next-generation gene-editing platforms to achieve more effective and lasting clinical outcomes. Collectively, these advances represent a paradigm shift in DMD management and offer renewed hope for improving survival and quality of life for affected individuals.

Humans↗

PubMed2025

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

IMPORTANCE: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration. OBJECTIVE: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023. Inclusion criteria were asymptomatic ATTR cardiac amyloid infiltration, defined as an absence of HF history, HF signs and symptoms, diuretic therapy, and plasma cell dyscrasia with evidence of myocardial uptake on bone scintigraphy. If plasma cell dyscrasia was present, histologic confirmation of ATTR amyloid was required. EXPOSURE: Asymptomatic ATTR cardiac amyloid infiltration. MAIN OUTCOMES AND MEASURES: The primary outcomes were all-cause and cardiovascular (CV) mortality. The secondary outcomes were unplanned HF hospitalization, unplanned CV-related hospitalization, and a composite outcome of CV mortality and HF hospitalization. RESULTS: The study comprised 485 patients with asymptomatic ATTR cardiac amyloid infiltration (mean [SD] age, 74.9 [9.9] years, 85.8% male, 112 [23.1%] with hereditary ATTR amyloidosis), with 369 (76.1%) having grade 2 or 3 and 116 (23.9%) having grade 1 cardiac uptake at baseline. Patients with grade 2 or 3 uptake exhibited significantly more cardiac functional and structural abnormalities vs patients with grade 1 uptake. At 3 years, compared with grade 1 uptake, patients with grade 2 or 3 uptake had greater development of HF (54.3% [95% CI, 47.7%-61.3%] vs 23.1% [95% CI, 14.8%-35.1%]), greater outpatient diuretic initiation and N-terminal pro-B-type natriuretic peptide progression (35.0% [95% CI, 28.0%-43.2%] vs 12.4% [95% CI, 6.3%-23.7%]), and greater HF hospitalization (8.7% [95% CI, 5.9%-12.9%] vs 0%) and unplanned CV hospitalization (20.0% [95% CI, 15.7%-25.3%] vs 4.3% [95% CI, 1.6%-11.3%]). Over a median follow-up of 37 months (IQR, 20-64 months), the all-cause death rate was similar between patients with grade 1 vs 2 and 3 uptake; however, those with grade 2 or 3 compared with grade 1 uptake had a significantly higher risk of CV mortality (unadjusted hazard ratio, 5.30; 95% CI, 1.92-14.65). CONCLUSIONS AND RELEVANCE: This study shows that asymptomatic ATTR cardiac amyloid infiltration encompasses a wide spectrum of disease severity, with patients with grade 2 or 3 cardiac uptake experiencing an increased rate of CV events and CV mortality and patients with grade 1 uptake experiencing a lower CV event rate and predominantly non-CV mortality. These findings support the use of disease-modifying treatments in asymptomatic patients with grade 2 or 3 uptake and highlight the need of large-scale studies to assess their role in grade 1 uptake.

Humans↗

PubMed2024

Editing Approaches to Treat Alpha-1 Antitrypsin Deficiency.

TOPIC IMPORTANCE: Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder most commonly due to a single G to A point mutation (E342K), leading to debilitating lung and/or liver disorders and is associated with increased mortality. The E342K point mutation causes a conformational change of the AAT protein resulting in its retention in liver hepatocytes. This reduces AAT secretion into the serum resulting in higher protease activities due to the lack of inhibition from AAT, causing damage to healthy lung tissue. The current standard of care for lung manifestations involves weekly IV augmentation therapy and is considered suboptimal for these patients. Furthermore, there is currently no approved treatment for liver manifestations. The unmet medical need for patients with AAT deficiency remains high, and new treatment options are needed to treat the underlying disease etiology. REVIEW FINDINGS: Advances in genomic medicines may enable treatment by editing the DNA or RNA sequence to produce wild-type AAT instead of the mutated AAT caused by the E342K mutation. One approach can be achieved by directing endogenous adenosine deaminases that act on RNA to the E342K RNA site, where they catalyze adenosine to inosine conversion through a process known as RNA editing. The A-I RNA change will be read as a G during protein translation, resulting in an altered amino acid and restoration of wild-type AAT secretion and function. SUMMARY: In this review, we will discuss the pathophysiology of AAT deficiency and emerging treatment options with particular focus on RNA editing as a disease-modifying treatment for both liver and lung disease.

alpha 1-Antitrypsin Deficiency↗

PubMed2026

Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn's disease: 5-year follow-up of the PROFILE trial.

BACKGROUND: The PROFILE trial previously reported better 48-week outcomes for patients with Crohn's disease who received top-down anti-TNF treatment from diagnosis, compared with a conventional step-up strategy. Through subsequent follow-up of PROFILE participants, we aimed to assess whether the benefit of top-down treatment from diagnosis results in modification of the long-term disease course. METHODS: PROFILE was a multicentre, open-label, randomised controlled trial completed in 40 hospitals in the UK, which included patients aged 16-80 years with newly diagnosed Crohn's disease. Eligible patients were randomly assigned via a secure online platform to a top-down (infliximab plus immunomodulator) or a step-up protocolised treatment strategy for 48 weeks, after which participants reverted to local standards of care. Objective outcome data were extracted for up to 5 years after the week 48 visit, including need for Crohn's-related abdominal surgery as the primary outcome. Data were analysed based on the original PROFILE randomisation and intention-to-treat population. Participants without long-term follow-up data were censored at the week 48 visit. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. The trial was registered with the ISRCTN registry, number 11808228 and is complete. FINDINGS: Between Dec 29, 2017, and Jan 5, 2022, 483 patients were assessed for inclusion. 389 patients were enrolled and randomly assigned (three patients were excluded due to ineligibility), 193 to top-down treatment and 193 to step-up treatment. Of the 386 participants in the PROFILE primary trial, 358 (93%) had post-week 48 records available for review (182 [51%] top-down and 176 [49%] step-up). Median follow-up was approximately 5 years from randomisation (1809 days [IQR 1300-2101]), by which point 172 (89%) of 193 patients in the step-up group and 191 (99%) of 193 patients in the top-down group had received biological or immunomodulator therapy. Relating to the primary outcome, during follow-up there were 28 Crohn's disease-related abdominal surgeries in 26 patients treated with a step-up approach versus six surgeries in six patients treated with a top-down approach. Time to surgery was shorter in the step-up group than the top-down group (adjusted hazard ratio [aHR] 5·23 [95% CI 1·99-13·76]; p=0·0008). For the secondary outcomes, incidence of Crohn's disease-related hospital admissions was higher in patients originally managed with step-up treatment versus top-down treatment (41 [21%] of 193 patients vs 22 [11%] of 193 patients); and time to first hospital admission was shorter with step-up treatment than with top-down treatment (aHR 2·01 [95% CI 1·18-3·41], p=0·017). Progression to B2 or B3 complications was also more frequent in those originally managed with step-up treatment compared with top-down treatment (32 [17%] of 192 patients vs 13 [7%] of 193 patients); with time to disease progression being shorter in the step-up group than in the top-down group (aHR 2·46 [95% CI 1·25-4·86]; p=0·010). There was no difference in safety outcomes between groups for either serious infections (12 [6%] of 193 step-up patients and 14 [7%] of 193 top-down patients) or malignancies (five patients [3%] and three patients [2%] respectively). INTERPRETATION: Early top-down anti-TNF treatment from diagnosis was associated with improved long-term outcomes at 5 years compared with step-up treatment and is suggestive of a disease-modifying effect in Crohn's disease. FUNDING: Wellcome and Celltrion.

Journal Article↗

PubMed2025

The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggressiveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect β-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies.

Humans↗

PubMedDate not supplied

Current management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is usually a relentlessly progressive disease leading to joint damage and disability. While the long-term value of disease-modifying drugs is still questioned, the quality of life of RA patients has improved, possibly reflecting the earlier more aggressive and multifaceted approach to management and/or the innate attenuation in the disease over recent years.

Adrenal Cortex Hormones↗

PubMed1992

Antireactive properties of "chondroprotective" drugs.

The medicinal therapy of osteoarthritis is based on the use of analgesics, NSAIDs and corticosteroids to relieve pain and inflammation. In addition, "chondroprotective" agents (CPA) are used to stop the evolution of the disease. In this review the biochemical and pharmacological activities of some of the most widely used CPAs are described. All of these show more or less marked antiinflammatory activities, which for some of them are the result of an inhibition of cyclo-oxygenase and of prostaglandin biosynthesis, in which case they should be more properly classified as mild NSAIDs. Only two of the CPAs reviewed, diacerein and D-glucosamine sulfate, elicit antiinflammatory and antireactive effects without significant inhibition of the prostaglandin biosynthesis. These agents have also remarkable chondroprotective effects, and only these two agents should be classified as true CPAs. In particular glucosamine sulfate, which naturally occurs in the human body and is almost devoid of toxicity, is suitable for long-term therapeutic use. This, with its chondrometabolic, antireactive and antiarthritic properties, represents the pharmacological rationale for the use of glucosamine sulfate as a disease-modifying agent in osteoarthritis.

Animals↗

PubMed1992

[The "Emmerich Arthritis Record", function and acceptance within the scope of an integrated treatment concept].

For a comprehensive model of rheumatoid arthritis treatment, we designed an arthritis manual for continuous treatment of chronic illness. One goal of introducing the manual to the patients was the improvement of communication between patient and different doctors and therapists. The first part includes of a doctor's documentation sheet and a patient calendar (6 months each) for daily self-documentation of drug compliance. The second part is a daily pain-rating scale. The 3-year evaluation of 655 patient manuals for 286 patients was analyzed to estimate the compliance in using the manual. Overall, 87% of diagnoses, 83% of disease-modifying anti-rheumatic drugs (DMARDs), 87% of non-steroidal anti-rheumatic drugs (NSAIDs) had been documented in the manual. Data indicates that the general practitioner and the rheumatologist accepted the manual form. In addition, 85% of the documented patients used the DMARDs, 74% used the daily pain score, and 43% the daily physiotherapy. Subgroup data (n = 130 RA patients) suggest additional results: 1) there was no difference in sociodemographic data between the patient manual user group and the non-user group; 2) the user group consisted of patients with higher disease activity (ARA-criteria), higher pain score, and negative mood pattern. Furthermore, the user group was more active in daily physiotherapy, ergotherapy, and balneotherapy.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Immunosuppressive activity of 15-deoxyspergualin (15-DOS) on various models of rheumatoid arthritis.

Based on the promising results obtained thus far in various auto-immune disease models, the authors have further elucidated the disease-modifying potential of the new immunosuppressive drug 15-deoxyspergualin (15-DOS) in models of inflammatory and chronic degenerative joint disease of adjuvant arthritis (AA) and collagen type-II induced arthritis (CIA) in Lewis rats and spontaneously developing polyarthritis in MRL/1 mice. Treatment of AA animals with 15-DOS starting with the day of adjuvant injection prevented the disorder from spreading to the non-injected extremity. The drug also reduced the arthritis index (47% inhibition). The adjuvant disease can thus be prevented nearly totally, even after discontinuation of drug application. Even when starting the therapy during the established disease, 15-DOS still exerts a protective action on the development of the adjuvant disease. In the present model of CIA, the animals showed the same progression as reported by others. Approximately 80% of the animals had bilateral hind paw swelling. The production of autoreactive anti-type-II collagen antibodies and also high levels of circulating rheumatoid factor (RF) can be demonstrated in the serum of CIA rats. Treatment of these animals with 15-DOS was very effective in inhibiting swelling of the joints. Average antibody titres were also depressed and circulating RF was reduced. Even when treatment with 15-DOS started on day 15 after CIA induction on established lesions of polyarthritis, not only a significant suppression of the paw diameters occurred, but also the humoral response (antibody formation) could be inhibited in animals with established CIA disease. The disorder of MRL/1 mice is characterized by the development of auto-antibodies most prevalently directed against double-stranded DNA (dsDNA) and type-II collagen. These mice also have circulating rheumatoid factor (RF) and develop histological changes in their joints characterized by pannus formation, cartilage and bone erosions. Treating MRL/1 mice with 15-DOS resulted in a decrease in the amount of auto-antibodies and inhibited developing polyarthritis. Even in an established disease, 15-DOS reduced circulating RF and increase in paw volume (signs of polyarthritis) was inhibited. These results suggest that 15-DOS might be used as a therapeutic agent for human RA and that this new immunosuppressive drug could be an effective nonsteroidal antirheumatic agent.

Animals↗