Consensus-Based Overarching Principles and Recommendations on the Use of Biosimilars in the Treatment of Inflammatory Arthritis in the Gulf Region.

BACKGROUND: Though biologic agents have significantly improved the treatment of inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis), high costs, stringent regulations, strict reimbursement criteria, and existing patents have limited patient access to treatments. While being highly similar in quality, safety, and efficacy to biologic reference products, biosimilars can reduce the financial burden and prevent underutilization of medication. OBJECTIVE: The objective of this initiative was to develop an evidence-based consensus of overarching principles and recommendations aimed at standardizing the use of biosimilars in treating inflammatory arthritis in the Gulf region. METHODS: A task force of practicing rheumatologists, a clinical pharmacist, a health economist, patients, regulators, and payors from across the Gulf region developed recommendations and overarching principles based on the outputs of a systematic literature review conducted to address Patient-Intervention-Comparison-Outcome (PICO) questions specific to key challenges regarding the use of biosimilars for the treatment of inflammatory arthritis in the region. As the data before 2017 have been previously reviewed in another publication, the current review focused on data published between January 2017 and August 2022 (PROSPERO ID CRD42022364002). Consensus on each statement required a level of agreement of 70% or greater. RESULTS: Consensus was reached for five overarching principles and nine recommendations by the task force. The principles emphasize the importance of improving the awareness, understanding, and perception of biosimilars, as well as the need for regulated regional real-world data generation and protocols to make biosimilars a viable and affordable treatment option for all patients. The consensus recommendations advocate the need for shared treatment decisions between rheumatologists and patients when considering biosimilars. They further recommend that confirmation of a biosimilar's efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the reference product has been approved. Finally, there is a need for pharmacovigilance and national health policies governing the adoption and prescription of biosimilars in clinical practice across the region. CONCLUSIONS: These are the first consensus recommendations for the Gulf region based on a systematic literature review and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines, integrating clinical evidence with clinical expertise to optimize decision making for the use of biosimilars in patients with inflammatory arthritis. They were formulated based on predominantly international data because of the limited regional data and therefore can be generalized to serve as recommendations for healthcare professionals in other parts of the world.

COVID-19 and reported mortality cases among rheumatic disease patients in Kuwait: Data from the Global Rheumatology Alliance registry.

Mycophenolate mofetil and rituximab have been shown to be considerably associated with poorer outcomes following SARS-CoV-2 infection. Such agents were associated with longer hospital stay as well as severe COVID-19 outcomes (infection-related complications, intensive care unit admission, and mortality). Using the data of the COVID-19 Global Rheumatology Alliance (GRA) registry of inflammatory rheumatic disease (IRD) patients in Kuwait, who had COVID-19 from March 2020 to March 2021, revealed 4 mortality cases (3 cases used CD-20 inhibitors as monotherapy and 1 case used mycophenolate mofetil/mycophenolic acid as monotherapy). This article describes the characteristics and course of disease among 4 patients with IRD who died following COVID-19 infection at Jaber Al Ahmed Hospital, Kuwait. The current series raises the intriguing prospect that IRD patients may have a varying risk of unfavorable clinical outcomes depending on the type of biological agents they were given. Rituximab and mycophenolate mofetil should be used with caution in IRD patients, particularly if they have concomitant comorbidities that put them at a high likelihood of developing severe COVID-19 outcomes.

Is Serum Uric Acid Level Associated with Disease Activity in Rheumatoid Arthritis Patients.

Background: An association between serum uric acid (UA) and disease activity in rheumatoid arthritis (RA) patients has not been well studied. We describe RA patients with high and normal UA and study its association with RA activity. Methods: Adult RA patients from the Kuwait Registry for Rheumatic Diseases (KRRD) were studied from February 2012 through March 2022. Patients with documented UA levels were included. UA of >357 µmol/L (6mg/dL) was considered high. Statistical comparison and correlation were made using multivariate logistic regression. Results: Overall, 1054 patients with documented UA. A total of 158 patients (15%) had high UA level with a mean of 409± 44.4µmol/L. The mean age for the high UA group and low UA group were 59.3 ± 10.7 years and 54.5 ± 12.4 years, respectively (p<0.001). 49.4% were female in high UA group, and 62.2% were female in low UA group, respectively (p<0.05). Logistic analysis showed an inverse relation between DAS28 and UA, as lower DAS28 score was associated with higher UA level (p=0.032) OR 1.39. There was a direct relation with HAQ, creatinine and UA. A higher HAQ is associated with a higher UA level (p=0.019) OR 0.78. High creatinine level is also associated with high UA level (p<0.001) OR 0.24. The use of antirheumatic drugs was similar among patients with high and normal UA. Conclusion: RA patients with a higher UA had a lower disease activity despite using similar antirheumatic drugs. The reasons behind this association need to be further studied.

Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity. OBJECTIVE: The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA. METHODS: Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross-sectional study conducted on 754 RA patients visits aged (21-79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14-item Questionnaire (paper or web-based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity. RESULTS: The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08-0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others. CONCLUSION: The findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.

Expert Opinion Guidance on the Detection of Early Connective Tissue Diseases in Interstitial Lung Disease.

There is a significant variation in symptoms and clinical presentation of connective tissue disorders (CTD) associated with interstitial lung disease (ILD) (CTD-ILD). This presents difficulties in the diagnosis and treatment of CTD-ILD. Early detection and treatment of CTD-ILD using a multidisciplinary approach have been shown to enhance patient outcomes. This exercise aims to explore clinical components to develop a screening tool for pulmonologists for early detection of CTD in ILD and to provide a framework for a multidisciplinary approach in managing CTD-ILD. This in turn will lead to early treatment of CTD-ILD in collaboration with rheumatologists. A panel of 12 leading rheumatologists from the Middle East and North Africa (MENA) region met virtually to select the most relevant clinical findings to aid in identifying CTD-ILD. Twelve panellists opted to investigate seven of the most common inflammatory autoimmune disorders. The panel discussed how to improve the early detection of CTD-ILD. Clinical characteristics were categorized, and a nine-item questionnaire was created. A biphasic algorithm was developed to guide early referral to a rheumatologist based on the presence of one of nine clinical features of CTD (Phase 1) or the presence of CTD-specific antibodies (Phase 2). A brief questionnaire has been developed to serve as a simple and practical screening tool for CTD-ILD detection. Additional research is needed to validate and evaluate the tool in longitudinal cohorts.

COVID-19 outcomes among rheumatic disease patients in Kuwait: Data from the COVID-19 Global Rheumatology Alliance (C19-GRA) physician registry.

PURPOSE: We aimed to assess the characteristics of inflammatory rheumatic disease (IRD) patients in Kuwait diagnosed with COVID-19 and the factors linked with hospitalization, complications, and mortality. METHODS: Data of IRD patients from Kuwait diagnosed with COVID-19 between March 2020 and March 2021, submitted to the COVID-19 Global Rheumatology Alliance physician-reported registry, were included in our analysis. Data on patients' age, gender, smoking, diagnosis, IRD activity, and other comorbidities were collected. Statistical Package for the Social Sciences (SPSS), version 25, was used for statistical analysis. RESULTS: A total of 52 patients were included, with a mean age of 55 years (±14). The majority of patients were ≤65 years (77%), female (77%), non-smokers (80.8%), and diagnosed with rheumatoid arthritis (67.0%). Of the included patients, 19.2%, 9.6%, and 7.7% reported having methotrexate monotherapy, antimalarials monotherapy, and interleukin-6 inhibitors monotherapy immediately before COVID-19, respectively. Most of the included patients (92.3%) were either in remission or had minimal/low disease activity, while others (7.7%) had moderate disease activity. Forty-three patients (82.7%) were hospitalized, while 11 patients (25.6%) required ventilation (invasive or non-invasive). Ten of the ventilated patients (90.9%) received glucocorticoids as part of the local protocol to treat severe COVID symptoms, and 4 patients (7.69%) died. The duration till symptom-free ranged between 0 to 30 days, with a mean value of 10 days (±6.5). CONCLUSION: The current study provides timely real-world evidence regarding characteristics and potential risk factors linked to poor COVID-19-related outcomes in the IRD population in Kuwait.

Therapeutic role of immunomodulators during the COVID-19 pandemic- a narrative review.

The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BACKGROUND: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region. METHODS: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission. FINDINGS: A total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission. INTERPRETATION: Remission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

Handling missing data in a rheumatoid arthritis registry using random forest approach.

Missing data in clinical epidemiological research violate the intention-to-treat principle, reduce the power of statistical analysis, and can introduce bias if the cause of missing data is related to a patient's response to treatment. Multiple imputation provides a solution to predict the values of missing data. The main objective of this study is to estimate and impute missing values in patient records. The data from the Kuwait Registry for Rheumatic Diseases was used to deal with missing values among patient records. A number of methods were implemented to deal with missing data; however, choosing the best imputation method was judged by the lowest root mean square error (RMSE). Among 1735 rheumatoid arthritis patients, we found missing values vary from 5% to 65.5% of the total observations. The results show that sequential random forest method can estimate these missing values with a high level of accuracy. The RMSE varied between 2.5 and 5.0. missForest had the lowest imputation error for both continuous and categorical variables under each missing data rate (10%, 20%, and 30%) and had the smallest prediction error difference when the models used the imputed laboratory values.

Accessibility to biologics and its impact on disease activity and quality of life in patients with rheumatoid arthritis in Kuwait.

OBJECTIVE: Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or patients with contraindications to cDMARDs or poor prognostic factors. The purpose of this study was to compare the prescription rates of biologics in Kuwaiti and non-Kuwaiti patients and to assess whether this had an impact on disease activity and quality of life in RA patients. METHODS: Data were extracted from the Kuwait Registry for Rheumatic Diseases. Adult patients who satisfied the ACR classification criteria for RA from four major hospitals in Kuwait were evaluated from February 2013 through May 2018. The treatment agents, disease activity, and quality of life of Kuwaiti patients were compared with non-Kuwaiti patients. RESULTS: A total of 1651 RA patients were included; 806 (48.8%) were Kuwaiti patients. Among Kuwaiti patients, 62.5% were on biologic drugs in comparison with 14% of non-Kuwaiti patients. In comparison with non-Kuwaiti patients, Kuwaiti patients had significantly lower numbers of swollen joints (p < 0.001) and disease activity score-28 scores (p = 0.02) and less steroid use (p < 0.001) yet a significantly higher health assessment questionnaire-disability index (p < 0.001). Regression analysis showed that DAS-28 scores were significantly associated with the treatment type (p < 0.001) and that nationality was significantly predictive of the treatment type (p < 0.001). CONCLUSION: In the setting of easy accessibility to treatment for Kuwaiti patients, biologics were prescribed by rheumatologists at a higher rate than for non-Kuwaitis. This may explain the lower disease activity and the lower rate of steroid use in Kuwaiti patients than non-Kuwaitis. KEY POINTS: • Significant discrepancies in the rates of prescribing biologic therapies between KP and NKP in Kuwait were observed. • Several treatment outcomes were significantly better in the KP group than in the NKP group even after adjustment of confounding factors. • The poor access to biologic therapies was suggested to limit the effectiveness of RA treatments in the NKP group.

Recommendation for the Management of Spondyloarthritis Patients in Kuwait.

OBJECTIVE: In 2016, ASAS and EULAR made joint recommendations for the management of patients with spondyloarthritis. Although Global and European perspectives are important, they cannot accurately reflect the situation for all patients in all countries and regions. As such, the group worked to tailor the existing international recommendations to suit the specific demographic needs of local populations in the Gulf region, with a specific focus on Kuwait. METHODS: Recommendations drafted following a PubMed search for relevant literature were reviewed and then underwent Delphi vote to reach consensus on those to be included. Advice for newly approved agents, including targeted synthetic disease-modifying anti-rheumatic drugs, was included based on the group's clinical experience. RESULTS: The resulting 41 recommendations are grouped into five categories covering key definitions and principles for the management and treatment of both axial and peripheral forms of spondyloarthritis. CONCLUSION: Through adaptation of existing guidelines and incorporating the current evidence and clinical experience of the members of the group, these recommendations have been developed to reflect the unique situation in Kuwait with regard to differing patient profiles, local culture and approved therapeutic approaches, and are designed to aid in clinical decision-making.

Influence of Ambient Air Pollution on Rheumatoid Arthritis Disease Activity Score Index.

Rheumatoid arthritis (RA) is a chronic autoimmune of an unknown etiology. Air pollution has been proposed as one of the possible risk factors associated with disease activity, although has not been extensively studied. In this study, we measured the relationship between exposure to air pollutants and RA activity. Data on RA patients were extracted from the Kuwait Registry for Rheumatic Diseases (KRRD). Disease activity was measured using disease activity score with 28 examined joints (DAS-28) and the Clinical Disease Activity Index (CDAI) during their hospital visits from 2013 to 2017. Air pollution was assessed using air pollution components (PM 10 , NO 2 , SO 2 , O 3 , and CO). Air pollution data were obtained from Kuwait Environmental Public Authority (K-EPA) from six different air quality-monitoring stations during the same period. Multiple imputations by the chained equations (MICE) algorithm were applied to estimate missing air pollution data. Patients data were linked with air pollution data according to date and patient governorate address. Descriptive statistics, correlation analysis, and linear regression techniques were employed using STATA software. In total, 1651 RA patients with 9875 follow-up visits were studied. We detected an increased risk of RA using DAS-28 in participants exposed to SO 2 and NO 2 with ß = 0 . 003 (95% CI: 0.0004-0.005, p < 0 . 01 ) and ß = 0 . 003 (95% CI: 0.002-0.005, p < 0 . 01 ), respectively, but not to PM 10 , O 3 , and CO concentrations. Conclusively, we observed a strong association between air pollution with RA disease activity. This study suggests air pollution as a risk factor for RA and recommends further measures to be taken by the authorities to control this health problem.

Kuwait association of rheumatology 2018 treatment recommendations for patients with rheumatoid arthritis.

The Kuwait Association of Rheumatology (KAR) aimed to develop a set of recommendations for the treatment of patients with rheumatoid arthritis (RA), tailored to the unique patient population and healthcare system of Kuwait. Each recommendation was developed based on expert opinion and evaluation of clinical practice guidelines from other international and national rheumatology societies. Online surveys were conducted to collate feedback on each KAR member's level of agreement (LoA) with definitions of disease-/treatment-related terms used and the draft recommendations. Definitions/recommendations achieving a pre-defined cut-off value of ≥ 70% agreement were accepted for inclusion. Remaining statements were discussed and revised at a face-to-face meeting, with further modifications until consensus was reached. A final online survey was used to collect feedback on each KAR member's LoA with the final set of recommendation statements on a scale of 0 (complete disagreement) to 10 (complete agreement). Group consensus was achieved on 66 recommendation statements, including 3 overarching principles addressing the pharmacological treatment and management of RA. Recommendations focused on treatment of early RA, established RA, patients with high-risk comorbidities, women during pregnancy and breastfeeding, and screening and treatment of opportunistic infections. The KAR 2018 Treatment Recommendations for RA reported here are based on a synthesis of other national/international guidelines, supporting literature, and expert consensus considering the Kuwaiti healthcare system and RA patient population. These recommendations aim to inform the clinical decisions of rheumatologists treating patients in Kuwait, and to promote best practices, enhance alignment and improve the treatment experience for patients.

Kuwait Recommendations on Vaccine Use in People with Inflammatory Rheumatic Diseases.

People with IRD are at increased risk of infection, and in 2011 EULAR made general recommendations for vaccination in these patients. Global and European perspectives are important, but they cannot accurately reflect the individual situations of patients in different countries and regions. Based on our clinical experience and opinions, we have sought to tailor the original EULAR recommendations to include advice for vaccination with new agents approved in the intervening years-including the new class of targeted synthetic disease-modifying antirheumatic drugs. We have also considered the specific demographic needs of patients in local populations in the Gulf region. The resulting 16 recommendations are grouped into four main categories covering general vaccination guidelines and best-practice for all patients with IRD, followed by a set of recommended vaccines against specific pathogens. The last two categories include recommendations for certain patient subgroups with defined risks and for patients who wish to travel.

Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A Description and a Comparison of Patients from the Kuwait Registry for Rheumatic Diseases.

OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients with rheumatoid arthritis (RA) and to compare their features with those of patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were evaluated for RN. Demographic and serological features and disease activity and severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22 (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and family history of an autoimmune rheumatic disease were similar. Obesity was more prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs. 152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3 ± 2.9 vs. 2 ± 2.7, p < 0.001), more tender joints (6.4 ± 8.8 vs. 4.2 ± 7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 ± 2.7 vs. 2.3 ± 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74 (8%), p = 0.034. The mean health assessment questionnaire score in RN patients was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low disease activity (means: disease activity score [DAS-28], 3.02; clinical disease activity index, 7.7; and simple disease activity index, 10.4), similar to the other group. While the rates of methotrexate treatment were comparable, biologic therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478 [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA patients. Patients with and without RN are similar in terms of demographics and serologic features, except for more obesity. However, patients with RN have more sicca symptoms, joint deformities, and painful and tender joints. Disease activity scores are low with more frequent biologic therapy.

Association of angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism with spondylarthropathies.

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion-deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0+/-11.36 years, age at onset of spondylarthropathy was 27.7+/-7.49 years and disease duration was 10.3+/-7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p=0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p=0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.

Exercise therapy for patients with diffuse idiopathic skeletal hyperostosis.

We evaluated the effect of exercise therapy on back pain, spinal range of motion (ROM), and disability in persons with diffuse idiopathic skeletal hyperostosis (DISH). Persons with symptomatic DISH received a daily exercise program for 24 weeks consisting of mobility, stretching, and strengthening exercises for the cervical, thoracic, and lumbar spine. It included 14 supervised sessions over 8 weeks. Outcomes included visual analogue scales (VAS) for pain, stiffness, and fatigue, 13 spinal measurements, the neck pain and disability scale, the Quebec back pain disability scale, the Bath Spondylitis Functional Index, and the MACTAR patient preference scale. Assessments were made at baseline, 8 weeks, and 24 weeks. Fifteen of 17 completed the study. Comparing week 24 with baseline, Schober's test improved significantly (p = 0.02), and VAS stiffness and left finger-to-floor test demonstrated a trend to improvement (p = 0.07 each). The physical measures, which were expected to improve with the exercise program, all moved in the direction expected, but had p values > 0.10. At 24 weeks, eight (53.3%) participants rated their status as improved, three (20%) as unchanged, and four (27%) were unsure about the benefit. The exercise program designed for DISH and tested in this study led to small improvements in physical measures which achieved significance only for lumbosacral flexion.

Role of radiation therapy in patients with a diagnosis of both systemic lupus erythematosus and cancer.

OBJECTIVE: To determine whether radiation therapy (RT) is denied to patients with lupus and cancer and whether RT causes unusual toxicity in those receiving it. METHODS: We included patients with lupus followed at the University of Toronto Lupus Clinic between 1972 and 2001 who had developed cancer. Demographic, clinical, and laboratory information were collected prospectively. Pathologic proof of cancer was obtained. Three radiation oncologists blinded for the diagnosis of lupus, the modalities of cancer treatment, and the hypothesis of the study reviewed patient data independently. They assessed the indication for RT and whether it should be curative or symptomatic. Recommendation for RT was considered when at least 2 of the 3 radiation oncologists concurred. A review of the literature was conducted. RESULTS: Forty cases of cancer in 38 patients were identified. Most frequent cancer sites were breast (8), skin (8), digestive (7), and hematologic (7). Median patient age was 58 years. The radiation oncologists recommended RT in 26 cases, either with a curative (14) or a symptomatic intent (12). Only 4 patients received RT, 3 with a curative intent and 1 with a symptomatic intent. None of these 4 patients developed any unusual toxicity. The literature review did not support the fact that lupus patients do not tolerate RT. CONCLUSION: Sixty-five percent of our lupus patients with cancer could have received curative or symptomatic RT but only 10% received it. No patient developed any toxicity. RT may be inappropriately withheld from lupus patients with cancer.