Patient Global Assessment Of Disease Research Articles

Real-World Effectiveness of Dupilumab in Adult and Adolescent Patients with Atopic Dermatitis: 2-Year Interim Data from the PROSE Registry.

There is a scarcity of data beyond 1 year for the use of dupilumab to treat atopic dermatitis (AD) in a real-world setting. This study aimed to evaluate the 2-year effectiveness of dupilumab among adult and pediatric patients with moderate-to-severe AD included in a real-world, longitudinal database study. PROSE is an ongoing, prospective, observational, multi-center registry in the USA and Canada, designed to collect real-world data from patients aged ≥ 12years with moderate-to-severe AD who initiate dupilumab in accordance with country-specific prescribing information. Assessments include body surface area affected by AD (BSA), Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), Pruritus Numerical Rating Scale (P-NRS), Patient-Oriented Eczema Measure (POEM), Patient Global Assessment of Disease (PGAD) questionnaire score, and occurrence of adverse events (AEs). Of 764 patients who enrolled in PROSE, 632 (83%) remained in the study at the time of this interim analysis. Improvements were observed at the first post-baseline clinic visit (approximately 3months) in the clinician-assessed measures (mean BSA and EASI scores); improvements were sustained throughout the 2-year period covered in the present study. Consistent and sustained improvements were also observed over the 2-year period in the patient-reported measures of P-NRS, POEM, and DLQI, and in the proportion of patients reporting "very good/excellent" in answer to the question in the PGAD questionnaire: "Considering all the ways in which your eczema affects you, indicate how well you are doing". Dupilumab treatment was well tolerated, with safety findings consistent with those previously reported in studies of dupilumab for the treatment of AD. In the real-world PROSE registry, patients with moderate-to-severe AD experienced sustained improvement in disease control, symptoms, and quality of life up to 2years after initiating dupilumab treatment. Safety data were consistent with the known safety profile of dupilumab. ClinicalTrials.gov identifier: NCT03428646. Video abstract (MP4 20,717kb).

Association of fear assessment in inflammatory rheumatic diseases (FAIR) questionnaire with ankylosing spondylitis quality of life and disease activity in patients with ankylosing spondylitis

Background/Aim: Fear against disease course, treatment, and limitations in family, work, and social life are commonly seen but mostly overlooked by physicians of patients with chronic inflammatory rheumatic diseases. Ankylosing spondylitis (AS) is a chronic inflammatory disease in young adults characterized by limitations in spinal mobility. The Fear Assessment (FAIR) Questionnaire was designed especially for patients with rheumatoid arthritis and spondyloarthritis to assess the level of fear from the patient’s perspective. Here we evaluate the FAIR score in AS patients and its association with disease activity, AS quality of life (ASQoL), depression, anxiety, and fatigue levels.
 Methods: This cross-sectional study included 79 patients with AS, and disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), AS-Disease Activity Score-C reactive protein, and functional status was assessed by Bath Ankylosing Spondylitis Functional Index (BASFI). Patient global assessment of disease and pain were scored on 0–10 cm visual analog scores. All patients completed FAIR and ASQoL questionnaires. The depression and anxiety were evaluated by Hospital Anxiety and Depression Scale (HADS), and fatigue was assessed by Fatigue Severity Scale (FSS).
 Results: The mean age of AS patients (62% male) was 41.7 (11.3) years. Most of the patients were on biological disease-modifying anti-rheumatic drugs (bDMARDs). The patients’ median BASDAI, ASDAS-CRP, and BASFI were 5.4 (range, 3.8–7.4), 3.83 (1.4), and 4.0 (range, 2.3–6.2), respectively. The overall FAIR, ASQoL, FSS, HADS-depression, and HADS-anxiety scores were 75 (range, 52–91), 9.6 (5.2), 5.4 (range, 4.1–7), 7.7 (4.4) and 9.6 (5.2), respectively. There were statistically significant correlations between disease activity indices and FAIR, ASQoL, FSS, and HADS scores. The FAIR scores significantly correlated with ASQoL, FSS, and HADS scores. The patients with active disease (BASDAI ≥ 4) had significantly higher levels of FAIR, ASQoL, FSS, and HADS. The best cut-off value for the FAIR score of AS patients with moderate to severe disease activity was 50 (AUC: 0.734, 95% CI [0.599–0.870], P = 0.002), with a sensitivity of 89.8%, specificity of 55%, positive likelihood ratio of 1.99, and Youden index of 0.45.
 Conclusion: This study shows that AS patients face a high level of fear which is associated with higher disease activity, higher risk of mood disorders, and lower quality of life. Physicians should not only focus on the physical improvement of the patient but also handle the fear of patients against their diseases and their treatment. This holistic approach will improve the dialogue between the physician and the patient, which will result in increased compliance with treatment and will raise the quality of care.

Safety and Biological Activity of Rozibafusp alfa, a Bispecific Inhibitor of Inducible Costimulator Ligand and B Cell Activating Factor, in Patients With Rheumatoid Arthritis: Results of a Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study.

ObjectiveTo assess the safety and biological activity of rozibafusp alfa, a first‐in‐class bispecific antibody–peptide conjugate targeting inducible costimulator ligand (ICOSL) and B cell activating factor (BAFF), in patients with rheumatoid arthritis (RA).MethodsThis phase 1b, double‐blind, placebo‐controlled, multiple ascending dose study included 34 patients (18–75 years; 82.4% female) with active RA (Disease Activity Score of 28 joints–C‐reactive protein [DAS28‐CRP] >2.6, on stable methotrexate) randomized 3:1 to receive rozibafusp alfa (n = 26, in four ascending dose cohorts of 70, 140, 210, and 420 mg) or a placebo (n = 8) subcutaneously once every 2 weeks for 10 weeks (six total doses), with 24 weeks of follow‐up. The primary end point was the incidence of treatment‐emergent adverse events (TEAEs). Additional assessments included serum pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and RA disease activity measures (DAS28‐CRP, Patient Global Assessment of Disease, and Physician Global Assessment of Disease).ResultsTEAEs occurred in 96.2% and 87.5% of patients receiving rozibafusp alfa and the placebo, respectively; most were mild or moderate in severity. Two (7.7%) patients treated with rozibafusp alfa reported serious TEAEs; none were considered treatment related. Multiple doses of rozibafusp alfa showed nonlinear PK (mean t 1/2 = 4.6–9.5 days) and dose‐related, reversible PD (>90% ICOSL receptor occupancy in 210‐ and 420‐mg cohorts; reduction in naïve B cells and increase in memory B cells in all cohorts). Five (20%) patients developed anti–rozibafusp alfa antibodies, with no apparent impact on safety. RA disease activity showed greater numerical improvement from baseline with rozibafusp alfa versus the placebo in the 210‐ and 420‐mg cohorts.ConclusionMultiple ascending doses of rozibafusp alfa were well tolerated, with PK and PD reflecting dual ICOSL and BAFF blockade. Findings support further clinical evaluation of rozibafusp alfa in autoimmune disease.

Minimal disease activity (MDA) in patients with recent-onset psoriatic arthritis: predictive model based on machine learning

BackgroundVery few data are available on predictors of minimal disease activity (MDA) in patients with recent-onset psoriatic arthritis (PsA). Such data are crucial, since the therapeutic measures used to change the adverse course of PsA are more likely to succeed if we intervene early. In the present study, we used predictive models based on machine learning to detect variables associated with achieving MDA in patients with recent-onset PsA.MethodsWe performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset contained data for the independent variables from the baseline visit and from follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a random forest–type machine learning algorithm to analyze the association between the outcome measure and the variables selected in the bivariate analysis. In order to understand how the model uses the variables to make its predictions, we applied the SHAP technique. We used a confusion matrix to visualize the performance of the model.ResultsThe sample comprised 158 patients. 55.5% and 58.3% of the patients had MDA at the first and second follow-up visit, respectively. In our model, the variables with the greatest predictive ability were global pain, impact of the disease (PsAID), patient global assessment of disease, and physical function (HAQ-Disability Index). The percentage of hits in the confusion matrix was 85.94%.ConclusionsA key objective in the management of PsA should be control of pain, which is not always associated with inflammatory burden, and the establishment of measures to better control the various domains of PsA.

Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?

BackgroundThe effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour...

Severe joint deformity and patient global assessment of disease are associated with discrepancies between sonographic and clinical remission: A cross-sectional study of rheumatoid arthritis patients

Objective Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. Methods In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2–5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. Results A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. Conclusions While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.

Validation of the Atopic Dermatitis Control Tool (ADCT\xa9) using a longitudinal survey of biologic-treated patients with atopic dermatitis

BackgroundThe Atopic Dermatitis Control Tool (ADCT©) is a brief patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control; six AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions. This study assessed the reliability, validity, and responsiveness of the ADCT in a longitudinal context, and provided thresholds to identify meaningful within-person change.MethodsData were from a prospective, longitudinal patient survey study of real-world effectiveness of dupilumab in patients with AD. Eligible patients completed a baseline survey before starting dupilumab and were followed at Months 1, 2, 3, and 6 post-initiation as they became eligible.ResultsPsychometric analyses confirmed internal consistency; Cronbach’s α coefficients were consistently above the threshold of 0.70 across each follow-up; item-to-total correlations were above the threshold of r ≥ 0.50. High correlations between the ADCT and the Dermatology Life Quality Index (DLQI) and skin pain supported construct validity, while known-group validity was shown on Patient Global Assessment of Disease (PGAD) overall well-being subgroups with worse AD-related overall well-being having higher mean ADCT total scores at all time points. The ability of the ADCT to detect change was confirmed; the threshold for meaningful within-person change was estimated to be 5 points. Finally, test–retest reliability was confirmed in subgroups of patients with stable PGAD responses.ConclusionsOur findings confirm that the ADCT is a valid and reliable tool for assessing AD control.

PMS70 PSYCHOLOGICAL SYMPTOMS AND TOTAL KNEE REPLACEMENT.

Psychological aspects are important when considering total knee replacement (TKR). The objective was to evaluate changes from baseline to 6-months post-surgery in anxiety and depression in patients who have undergone TKR according to OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) responder criteria to the intervention. This was a prospective cohort study of patients with osteoarthritis who have undergone TKR. While on the waiting list and 6-monts post-surgery, patients fulfilled several questionnaires: Hospital Anxiety and Depression Scale (HADS-a and HADS-d), WOMAC questionnaire and questions about patient global assessment of disease. OMERACT-OARSI responder criteria were based on a combination of absolute and relative change of WOMAC pain and function, and global patient’s assessment. HADS-a and HADS-d baseline and change scores were compared among responders and non-responders by the Wilcoxon test. 278 patients fulfilled baseline and 6-monts pot-surgery questionnaires. There were 40 (14.4%) patients classified as non-responders. At baseline, the mean (SD) scores were 6.6 (4.3) and 8.1 (5.1) for HADS-a (p=0.08) and 5.9 (3.5) and 7.1 (4.4) for HADS-d (p=0.09) in non-responders and responders, respectively. Regarding changes in HADS-a at 6-months, the non-responders experienced a worsening of -1.4 (SD, 4.4) points while responders had an improvement of 3.2 (SD, 4.9) points (p < 0.001). Changes at 6-months in HADS-d were also a worsening of - 1.3 (SD, 4.4) among non-responders, and an improvement of 2.6 (SD, 4.4) among responders (p < 0.001). :In patients undergoing TKR, psychological aspects get worse when the outcome measured by responder criteria based on changes in pain, function and global assessment is not met. Greater attention should be placed to mental health in these patients.

Responder Threshold for Patient-Oriented Eczema Measure (POEM) and Children's Dermatology Life Quality Index (CDLQI) in Adolescents with Atopic Dermatitis.

IntroductionThe Patient-Oriented Eczema Measure (POEM) assesses patient-reported frequency of atopic dermatitis (AD) symptoms, while the Children’s Dermatology Life Quality Index (CDLQI) measures the impact of skin disease on health-related quality of life (HRQoL) in children. There is currently no threshold for clinically meaningful within-person change in POEM or CDLQI scores in adolescents. Here we empirically derive within-person thresholds of meaningful within-person change in POEM and CDLQI scores in adolescents with moderate-to-severe AD.MethodsData were used from a phase 3, randomized, double-blind, placebo-controlled trial of dupilumab in adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD. Anchor-based methods were employed using the mean change in POEM and CDLQI scores from baseline to week 16 linked with a 1-point improvement in Patient Global Assessment of Disease (PGAD), a score of “a little better” on the Patient Global Assessment of Treatment effect (PGAT), a 50–74% improvement from baseline in the Eczema Area and Severity Index (EASI-50–74), and a 1-point improvement in Investigator’s Global Assessment (IGA) score.ResultsA mean change of − 7.8 and − 5.6 in the POEM score was associated with PGAD and PGAT anchors, respectively. EASI-50–74 was associated with a mean change in POEM score of − 8.2, while the IGA anchor was associated with a mean change of − 7.9 in POEM score. The mean changes in CDLQI score associated with PGAD and PGAT anchors were − 6.4 and − 6.6, respectively, while CDLQI mean scores changed by − 8.3 and − 8.0 for the EASI and IGA anchors, respectively.ConclusionIn adolescents (aged ≥ 12 to < 18 years) with moderate-to-severe AD, a within-person change of 6–8 points in POEM and CDLQI scores, independently, can be considered a reasonable responder threshold for clinically meaningful change in each of the two scales, respectively.Trial RegistrationClinicalTrials.gov Identifier: NCT03054428.FundingSanofi and Regeneron Pharmaceuticals, Inc.Electronic supplementary materialThe online version of this article (10.1007/s13555-019-00333-2) contains supplementary material, which is available to authorized users.

Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial.

ObjectivesTo compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX.MethodsIn the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36]).ResultsPROs improved following tofacitinib and MTX treatment: benefits were sustained over 24 months. Patients receiving tofacitinib reported earlier responses which were significantly different between each tofacitinib dose and MTX at month 3 through month 24. At month 6 (primary end point), significant improvements versus MTX were observed in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 5/8 domain scores and FACIT-F with tofacitinib 5 mg two times per day; all PROs, except SF-36 Mental Component Summary Score and Medical Outcomes Survey-Sleep, with tofacitinib 10 mg two times per day. At month 6, the proportion of patients reporting improvements ≥minimum clinically important difference were significant versus MTX with tofacitinib 5 mg two times per day in PtGA and 3/8 SF-36 domains; and with tofacitinib 10 mg two times per day in PtGA, pain, HAQ-DI, SF-36 PCS, 4/8 domains and FACIT-F.ConclusionsPatients with rheumatoid arthritis receiving tofacitinib 5 and 10 mg two times per day monotherapy versus MTX reported statistically significant and clinically meaningful improvements in multiple PROs over 24 months; onset of benefit with tofacitinib treatment occurred earlier.Trial registration numberNCT01039688.

Impact of tofacitinib on patient outcomes in rheumatoid arthritis - review of clinical studies.

Rheumatoid arthritis is a chronic, progressive autoimmune disease associated with inflammation and destruction of joints and systemic effects, which result in significant impact on patient’s quality of life and function. Tofacitinib was approved for the treatment of rheumatoid arthritis in the USA in 2012 and subsequently in other countries, but not by the European Medicines Agency. The goal of this review was to evaluate the impact of tofacitinib on patient-reported and patient-specific outcomes from prior clinical studies, focusing on quality of life, functionality, pain, global disease assessment, major adverse consequences, and withdrawals. A total of 13 reports representing 11 clinical studies on tofacitinib in rheumatoid arthritis were identified through PubMed and reference lists in meta-analyses and other reviews. Data on improvements in patient-driven composite tools to measure disease activity in rheumatoid arthritis, such as the Health Assessment Questionnaire, served as a major outcome evaluated in this review and were extracted from each study. Additional data extracted from those clinical studies included patient assessment of pain (using a 0–100 mm visual analog scale), patient global assessment of disease (using a 0–100 mm visual analog scale), patient withdrawals, withdrawals due to adverse effects or lack of effect, and risk of serious adverse effects, serious infections, and deaths. Tofacitinib 5 mg bid appears to have a favorable impact on patient outcomes related to efficacy and safety when compared with baseline values and with comparator disease-modifying antirheumatic drugs and placebo. Improvements were seen in the composite and individual measures of disease activity. Serious adverse effects, other adverse consequences, overall withdrawals, and withdrawals due to adverse effects and lack of efficacy are similar or more favorable for tofacitinib versus comparator disease-modifying antirheumatic drugs and placebo. At this point, tofacitinib appears to have an important role in the treatment of rheumatoid arthritis through improvement in these patient outcomes. However, it may require years of additional clinical studies and postmarketing surveillance to fully characterize the benefit-to-risk ratio of tofacitinib in a larger and diverse patient population.

Serum soluble bone turnover biomarkers in psoriatic arthritis and psoriatic spondyloarthropathy.

Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA.

Health status has improved more in women than in men with rheumatoid arthritis from 1994 to 2009: results from the Oslo rheumatoid arthritis register

ObjectiveTo examine changes in patient reported outcome measures (PROs) over 15 years in a representative population of patients with rheumatoid arthritis (RA), with a particular focus on gender differences.Patients and...

SAT0372 The Burden of Gout in Patients Included in Clinical Trials: A Systematic Review

BackgroundThe impact of gout on patients’ lives is still largely unknown.ObjectivesWe performed a systematic review of the baseline characteristics of participants of acute and chronic gout trials as an indirect...

Ethnic Influence in Clinical and Functional Measures of Brazilian Patients with Spondyloarthritis

Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients. A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%). White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-α agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001). Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites.

Pulse Pamidronate therapy in NSAID refractory ankylosing spondylitis. Is it effective?–An open label study

Objective To assess the efficacy of pulse Pamidronate therapy in NSAID refractory ankylosing spondylitis (AS). Patients Fifty two patients of ankylosing spondylitis (fulfilling modified New York criteria), refractory to NSAID and having active disease were enrolled. Active disease was defined as BASDAI = 4 and/or early morning stiffness = 45 minutes despite NSAID therapy. Intervention Monthly intravenous Pamidronate infusions (60 mg) for a period of 6 months along with current NSAID. Primary outcome measure was improvement in BASDAI at the end of therapy. Secondary outcome measures included improvement in BASDAI = 25%, BASFI, metrology parameters, visual analogue scales for pain and global assessment of disease, ESR, CRP, MMP-3 and quality of life domains. Results Out of 52 patients enrolled [47 men; mean age 36.2 years (range 22-53 years) and mean disease duration 7.2 years (3-25 years)], 47 patients completed the study. At 6 months, there were significant improvement in BASDAI ( P < 0.005), BASFI ( P < 0.005), pain ( P < 0.005) and patient global assessment of disease ( P < 0.005) and lateral flexion (P<0.05). However, BASDAI >25% reduction was seen in 29.6% patients only. In addition, quality of life, HAQ and serological markers MMP-3, ESR and CRP were not significantly altered. Most common adverse effects included arthralgias and myalgias, 22.5% each, following initial infusions. There were five withdrawals; two defaults and one for hip joint replacement and two for asymptomatic rise in serum creatinine. Conclusion Pamidronate has modest efficacy in improving the patient reported outcome variables in NSAID refractory AS.

Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled Efficacy and Tolerability Study of Tramadol Extended Release for the Treatment of Osteoarthritis Pain in Geriatric Patients

Background: Once-daily tramadol extended release (ER) was evaluated for 12 weeks in a randomized, double-blind, placebo-controlled, parallel-group study in 1020 patients with osteoarthritis of the knee or hip. As previously reported, compared with placebo, the results of the study showed that patients treated with tramadol ER had significant improvement in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and in pain-related sleep parameters. Objective: Because chronic/persistent arthritis pain is common in geriatric patients, this post hoc analysis evaluated the efficacy and tolerability of tramadol ER in geriatric patients 65 years or older (n = 317) from this study. Methods: In the original study, the co-primary efficacy variables to evaluate the efficacy and tolerability of 100-, 200-, 300-, and 400-mg doses of tramadol ER were the WOMAC Osteoarthritis Index subscale scores for pain (0-500) and physical function (0-1700), and patient global assessment of disease (0-100). Secondary efficacy variables included arthritis pain intensity, 36-Item Short-Form Health Survey, daily pain diaries, sleep parameters, and tolerability assessments. Patients rated their arthritis pain utilizing a 100-mm visual analog scale (VAS) (0 = no pain, 100 = extreme pain). Sleep parameters were evaluated based on a 100-mm VAS (0 = never, 100 = always). Results: A total of 317 patients 65 years or older were included in the analysis (186 women, 131 men). Compared with placebo, this analysis found a significant improvement from baseline to the final visit in the co-primary efficacy variables of pain (least-squares [LS] mean [SE], 108.7 [16.9]; P ≤ 0.05) and physical function (LS mean [SE], 366.4 [57.7]; P ≤ 0.05) subscale scores of the WOMAC Osteoarthritis Index; the patient global assessment of disease activity (LS mean [SE], 27.9 [3.9]; P ≤ 0.01) for the tramadol ER 300-mg group; and for the pain-related sleep effects for less awakenings by pain in the morning (100-, 200-, and 300-mg groups; P ≤ 0.05), less awakenings by pain during the night (200- and 300-mg groups; P ≤ 0.035), significantly better overall sleep quality (200-mg group only; P = 0.037), and less trouble falling asleep due to pain (200-mg group only; P = 0.025). Commonly reported adverse events in patients 65 years or older treated with tramadol ER included constipation (27.5%), nausea (23.4%), dizziness (22.7%), and headache (15.6%). Conclusions: This post hoc analysis suggests that the tramadol ER 300-mg dose was associated with statistically significant improvement in pain intensity and physical function, and for most of the pain-related sleep effects among these geriatric patients with moderate chronic/persistent pain.

Comparison of tenoxicam and bromazepan in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled trial

Fibromyalgia is a painful syndrome of non-articular origin, predominantly involving muscles, and the commonest cause of chronic widespread musculoskeletal pain. The diversity of therapeutic programs for patients with fibromyalgia reflects both the lack of a known pathophysiology for this disorder and the low efficacy of the current therapies. We studied the efficacy of tenoxicam and bromazepan in the treatment of patients with fibromyalgia. One hundred and sixty-four patients from our Rheumatology Outpatient Clinic fulfilling the American College of Rheumatology criteria for the classification of fibromyalgia, with widespread pain at study entry. Each of the 164 patients was randomly assigned to 1 of 4 treatment groups: double placebo (P), tenoxicam (20 mg) + placebo (T), bromazepan (3 mg) + placebo (B), or tenoxicam (20 mg) + bromazepan 3 mg (TB). Patient global assessment of disease, pain, sleep quality, morning stiffness, and number of tender points were evaluated at baseline and 8 weeks afterwards. At the end of the trial, 17%, 10%, 12%, and 29% of the P, T, B, and TB patients, respectively, had clinical improvement. A statistically significant difference was found only between the T and TB groups. Our data indicate that treatment with tenoxicam + bromazepan can be effective for some patients with fibromyalgia, but the differences with the placebo group were neither clinically nor statistically significant.