scholarly journals Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial

2015 ◽  
Vol 43 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Yvonne C. Lee ◽  
Elena Massarotti ◽  
Robert R. Edwards ◽  
Bing Lu ◽  
ChihChin Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Pain Intensity ◽  
Short Form ◽  
Experimental Pain ◽  
Study Drug ◽  
Widespread Pain ◽  
Double Blind ◽  
Link Type ◽  
Average Pain Intensity ◽  
Average Pain

Objective.Clinical trials have shown that serotonin norepinephrine reuptake inhibitors, such as milnacipran, decrease pain in noninflammatory pain conditions such as fibromyalgia and osteoarthritis. We examined the effect of milnacipran on self-reported pain intensity and experimental pain sensitivity among patients with rheumatoid arthritis (RA) with widespread pain and stable RA disease activity.Methods.In this double-blind, crossover study, patients with RA with widespread pain, receiving a stable treatment regimen, were randomized (by a random number generator) to receive milnacipran 50 mg twice daily or placebo for 6 weeks, followed by a 3-week washout and crossed over to the other arm for the remaining 6 weeks. The primary outcome was change in average pain intensity, assessed by the Brief Pain Inventory short form. The sample size was calculated to detect a 30% improvement in pain with power = 0.80 and α = 0.05.Results.Of the 43 randomized subjects, 41 received the study drug, and 32 completed the 15-week study per protocol. On a 0–10 scale, average pain intensity decreased by 0.39 (95% CI −1.27 to 0.49, p = 0.37) more points during 6 weeks of milnacipran treatment compared with placebo. In the subgroup of subjects with swollen joint count ≤ 1, average pain intensity decreased by 1.14 more points during 6 weeks of milnacipran compared with placebo (95% CI −2.26 to −0.01, p = 0.04). Common adverse events included nausea (26.8%) and loss of appetite (9.7%).Conclusion.Compared with placebo, milnacipran did not improve overall, self-reported pain intensity among subjects with widespread pain receiving stable RA medications. Trial registration:ClinicalTrials.govNCT01207453.

scholarly journals Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Karin Due Bruun ◽  
Kirstine Amris ◽  
Henrik Bjarke Vaegter ◽  
Morten Rune Blichfeldt-Eckhardt ◽  
Anders Holsgaard-Larsen ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Low Dose ◽  
Controlled Trial ◽  
Muscle Performance ◽  
Double Blind ◽  
Intention To Treat ◽  
Average Pain Intensity ◽  
Average Pain ◽  
Secondary Outcomes ◽  
Low Dose Naltrexone

Abstract Background Low-dose naltrexone (LDN) is used widely as an off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with a high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last 7 days in women with fibromyalgia. Methods A single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a 4-week titration phase. The primary outcome is change in average pain intensity (during the last 7 days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e., tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers. Discussion This study will contribute with high-level evidence on the efficacy of low-dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia. Trial registration EudraCT 2019-000702-30. Registered on 12 July 2019. ClinicalTrials.gov NCT04270877. Registered on 17 February 2020

scholarly journals Low dose naltrexone for the treatment of fibromyalgia: Protocol for a double-blind, randomized, placebo-controlled trial

2021 ◽  
Author(s):  
Karin Due Bruun ◽  
Kirstine Amris ◽  
Henrik Bjarke Vaegter ◽  
Morten Rune Blichfeldt-Eckhardt ◽  
Anders Holsgaard-Larsen ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Low Dose ◽  
Controlled Trial ◽  
Muscle Performance ◽  
Double Blind ◽  
Intention To Treat ◽  
Average Pain Intensity ◽  
Average Pain ◽  
Secondary Outcomes ◽  
Low Dose Naltrexone

Abstract Background Low dose naltrexone (LDN) is used widely as off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last seven days in women with fibromyalgia.Methods A single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years and diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a four-week titration phase. The primary outcome is change in average pain intensity (during the last seven days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e. tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers.Discussion This study will contribute with high-level evidence on the efficacy of low dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia.Trial registration: EudraCT number 2019-000702-30 (registered on 2019-07-12). ClincalTrials.gov Identifier: NCT04270877 (registered on 2020-02-17).

Efficacy and Safety of Belimumab in Patients with Rheumatoid Arthritis: A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study

2013 ◽  
Vol 40 (5) ◽  
pp. 579-589 ◽  
Author(s):  
William Stohl ◽  
Joan T. Merrill ◽  
James D. McKay ◽  
Jeffrey R. Lisse ◽  
Z. John Zhong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Phase Ii ◽  
B Lymphocyte ◽  
Tumor Necrosis Factor Inhibitor ◽  
Open Label ◽  
Double Blind ◽  
Acr20 Response ◽  
Link Type ◽  
American College Of Rheumatology

Objective.To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA).Methods.Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response.Results.Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups.Conclusion.In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812]

scholarly journals Postoperative topical analgesia of hemorrhoidectomy with policresulen and cinchocaine: a prospective and controlled study

2014 ◽  
Vol 41 (2) ◽  
pp. 92-98 ◽  
Author(s):  
Ilario Froehner Junior ◽  
Paulo Gustavo Kotze ◽  
Juliana Gonçalves Rocha ◽  
Eron Fábio Miranda ◽  
Maria Cristina Sartor ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Bowel Movement ◽  
Controlled Study ◽  
Control Group ◽  
Oral Medications ◽  
Average Pain Intensity ◽  
Average Pain ◽  
The Mean ◽  
Double Blinded ◽  
Topical Analgesia

OBJECTIVE: To evaluate the effects of topical policresulen and cinchocaine in the postoperative pain behavior of open hemorrhoidectomy.METHODS: We conducted a prospective, double-blinded, controlled study. The control group received the usual guidelines with oral medications. The topical treatment group received, in addition, the application of the ointment and was comprised of two subgroups (policresulen + cinchocaine, and placebo). Pain intensity was recorded with the visual analogue scale.RESULTS: 43 patients were operated on: control group - n = 13, one excluded; placebo - n = 15; and policresulen + cinchocaine - n = 15. The mean age was 45.98 years and 37.2% were men. The average pain intensity was 4.09 (immediate postoperative), 3.22 (hospital discharge), 5.73 (day 1) , 5.77 (day 2), 5.74 (day 3), 5.65 (day 7), 5.11 (day 10), 2.75 (day 15) and 7.70 (first bowel movement), with no difference between groups in all periods.CONCLUSION: This study showed no reduction in pain after hemorrhoidectomy with the use of topical policresulen and cinchocaine.

Comparison of Concurrent and Retrospective Pain Ratings during Rehabilitation Following Anterior Cruciate Ligament Reconstruction

2004 ◽  
Vol 26 (4) ◽  
pp. 610-615 ◽  
Author(s):  
Britton W. Brewer ◽  
Allen E. Cornelius ◽  
Judy Van Raalte ◽  
John C. Brickner ◽  
Howard Tennen ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Anterior Cruciate Ligament Reconstruction ◽  
Pain Intensity ◽  
Ligament Reconstruction ◽  
Cruciate Ligament ◽  
Cruciate Ligament Reconstruction ◽  
Average Pain Intensity ◽  
Pain Ratings ◽  
Average Pain ◽  
Anterior Cruciate

The accuracy of retrospective ratings of pain intensity was examined in a sample of 72 men and 36 women undergoing rehabilitation following anterior cruciate ligament (ACL) reconstructive surgery. Participants completed daily ratings of current, worst, and average pain intensity for the first 42 days of rehabilitation. Participants provided retrospective ratings of worst and average pain intensity twice for a 7-day period (on Days 7 and 21) and once for a 30-day period (on Day 30). Correlations between concurrent and retrospective pain ranged from .74 to .88. Retrospective pain ratings consistently overestimated concurrent pain ratings, but were generally not biased by current pain. The results suggest that retrospective pain ratings can substitute for concurrent pain ratings if the tendency toward overestimation is taken into account.

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

scholarly journals Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

2019 ◽  
Vol 78 (6) ◽  
pp. 754-760 ◽  
Author(s):  
Sudha Visvanathan ◽  
Stefan Daniluk ◽  
Rafał Ptaszyński ◽  
Ulf Müller-Ladner ◽  
Meera Ramanujam ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Primary Endpoint ◽  
Study Drug ◽  
Nuclear Factor Κb ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Autoantibody Production ◽  
Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

scholarly journals Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001040 ◽  
Author(s):  
Vibeke Strand ◽  
Eduardo Mysler ◽  
Robert J Moots ◽  
Gene V Wallenstein ◽  
Ryan DeMasi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Patient Reported Outcomes ◽  
Short Form ◽  
Controlled Trial ◽  
Inadequate Response ◽  
Link Type ◽  
Combination Treatments ◽  
Sf 36 ◽  
Patient Reported ◽  
Phase Iiib

ObjectiveTo provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis (RA) with inadequate response to MTX (MTX-IR).MethodsORAL Strategy (NCT02187055), a phase IIIB/IV, head-to-head, randomised controlled trial, assessed non-inferiority between tofacitinib 5 mg two times per day monotherapy, tofacitinib 5 mg two times per day+MTX and ADA 40 mg every other week+MTX. PROs assessed included the following: Patient Global Assessment of disease activity (PtGA), Pain, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue and 36-Item Short-Form Health Survey (SF-36) summary and domain scores.ResultsSubstantial improvements from baseline were reported across all PROs in all treatment arms, which, in the majority, met or exceeded minimum clinically important differences. Compared with tofacitinib monotherapy, tofacitinib+MTX combination treatment conferred significantly greater improvements in PtGA, Pain and SF-36 physical component summary scores at month 6. Statistically or numerically greater improvements were often, but not uniformly, reported for combination treatments compared with tofacitinib monotherapy at other time points.ConclusionTreatment with tofacitinib+MTX, ADA+MTX and tofacitinib monotherapy resulted in clinically meaningful improvements in PROs in MTX-IR patients with RA. These were comparatively greater with combination treatments versus tofacitinib monotherapy, although differences between treatment arms were small, limiting our ability to confer clinical meaning.Trial registration numberNCT02187055.

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