POS1025 TOFACITINIB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND PROBABLE DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF TWO PHASE 3 CLINICAL TRIALS

Background:Depression and anxiety are highly prevalent in patients (pts) with psoriatic arthritis (PsA),1 with inflammation a key pathogenic feature of depression in these pts.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. It acts by modulating immune and inflammatory responses. The link between major depressive disorder/generalised anxiety disorder (MDD/GAD), inflammation and tofacitinib effectiveness has not been fully explored.Objectives:Analyse the prevalence of probable MDD/GAD in pts with PsA initiating tofacitinib treatment and the impact of baseline (BL) probable MDD/GAD status on tofacitinib efficacy in these pts.Methods:This was a post hoc analysis of data from pts who received tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO), pooled from two Phase 3 trials (12-month OPAL Broaden [NCT01877668];3 6-month OPAL Beyond [NCT01882439]4). Pts with BL probable MDD and/or GAD were identified by a Short Form-36 Health Survey (SF-36) Mental Component Summary score (MCS) ≤38. Pt demographics/BL characteristics and outcomes were stratified by the presence (SF-36 MCS ≤38) or absence (SF-36 MCS >38) of BL probable MDD/GAD. At Months (M)3/6/9/12, changes from BL in SF-36 MCS were evaluated, and efficacy assessed by the proportions of pts who achieved: Psoriatic Arthritis Disease Activity Score (PASDAS) ≤3.2, Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥0.35 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) improvement ≥4. BL global pain was measured via visual analogue scale.Results:Of the 706 pts included in this analysis, BL probable MDD/GAD was identified in 46.2%, 44.9% and 46.2% of pts in the tofacitinib 5 mg BID (108/234), tofacitinib 10 mg BID (106/236) and PBO (109/236) groups, respectively. BL disease activity was similar across the three treatment groups, independent of probable MDD/GAD status (mean PASDAS: 6.1–6.4 in pts with vs 5.8–6.1 in pts without probable MDD/GAD). In the tofacitinib 5 mg BID group, mean BL scores for HAQ-DI (1.4 vs 1.0), FACIT-F total score (20.5 vs 32.4) and global pain (61.3 vs 51.5) indicated worse disability, fatigue and pain, respectively, for pts with vs without BL probable MDD/GAD. Similar findings were seen in the tofacitinib 10 mg BID and PBO groups. At M3, improvements from BL in SF-36 MCS in pts with probable MDD/GAD were numerically, but not significantly, greater with tofacitinib 5 and 10 mg BID vs PBO, and these changes were largely sustained to M12 (Figure 1a). At M3, numerically greater proportions of pts achieved improvements in PASDAS, HAQ-DI and FACIT-F with tofacitinib 5 or 10 mg BID vs PBO, regardless of BL probable MDD/GAD status (Figure 1b–d). Through M3–12, the proportions of pts who achieved PASDAS ≤3.2 with tofacitinib 5 or 10 mg BID were generally significantly greater in pts without vs with probable MDD/GAD (Figure 1b). At all timepoints, rates of improvement in HAQ-DI with tofacitinib 5 mg BID were numerically greater in pts with vs without probable MDD/GAD, whereas the opposite was true for tofacitinib 10 mg BID (Figure 1c). FACIT-F improvement rates with tofacitinib 10 mg BID were consistently numerically greater in pts with vs without probable MDD/GAD, while findings were mixed for tofacitinib 5 mg BID (Figure 1d).Conclusion:Around 46% of pts with PsA treated with tofacitinib had BL probable MDD/GAD (SF-36 MCS ≤38). Pts with BL probable MDD/GAD treated with tofacitinib had sustained changes in SF-36 MCS. Rates of clinical improvement with tofacitinib were generally greater in pts without vs with probable MDD/GAD, whereas findings for disability and fatigue improvements varied between tofacitinib doses. Further research is required to evaluate the relationship between PsA and depression, to improve treatment targets and the quality of life of pts with PsA.References:[1]Zhao et al. Clin Rheumatol 2020; 39: 217-225.[2]Mathew & Chandran. Rheumatol Ther 2020; 7: 287-300.[3]Mease et al. N Engl J Med 2017; 377: 1537-1550.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Deeks, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Laure Gossec Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Agustí Sellas-Fernández: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Monica Valderrama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Susana Gómez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

Comparing Efficacy and Safety of Empirical vs. Guided Therapy for Non-cardiac Chest Pain: A Pragmatic Randomized Trial

Background: Non-cardiac chest pain is common with two-thirds due to gastroesophageal reflux disease (GERD).Objective: To evaluate the effectiveness and safety of guided vs. empirical therapy in non-cardiac chest pain.Methods: Adults with normal angiogram or stress test were randomized into either a guided or empirical group. In the guided group, after the ambulatory pH-impedance test, if GERD then dexlansoprazole 30 mg/day for 8 weeks, but if functional or hypersensitive chest pain, then theophylline SR 250 mg/day for 4 weeks. In the empirical group, dexlansoprazole 60 mg/day was given for 2 weeks. The primary outcome was global chest pain visual analog score (VAS) and secondary outcomes were Quality of Life in Reflux and Dyspepsia (QOLRAD), GERD questionnaire (GERDQ), and pH parameters, all determined at baseline, 2nd and 8th weeks.Results: Of 200 screened patients, 132 were excluded, and of 68 randomized per-protocol, 33 were in the guided group and 35 in the empirical group. For between-group analysis, mean global pain scores were better with guided vs. empirical group at 8th week (P = 0.005) but not GERDQ or QOLRAD or any of pH measures (all P > 0.05). For within-group analysis, mean QOLRAD improved earliest at 8th week vs. baseline (P = 0.006) in the guided group and 2nd week vs. baseline (P = 0.011) in the empirical group but no differences were seen in other secondary outcomes (P > 0.05). No serious adverse events were reported.Conclusions: Guided approach may be preferred over short-term empirical therapy in symptom response, however QOLRAD, acid-related symptoms, or pH measures are not significantly different (trial registration ID no. NCT03319121).

A Literature Review of the Effects of Self-Myofascial Release with a Foam Roller on Human Fascial System and Cardiovascular Function

PURPOSE: Self-myofascial release (SMR) using a foam roller is a popular intervention used to improve flexibility and restore skeletal muscles, fascia, tendons, ligaments and soft-tissue extensibility. However, the mechanism about the effects of SMR on flexibility, delayed onset of muscle soreness and arterial stiffness has not been elucidated. The purpose of this review is to provide basic knowledge for the mechanism about the effects of SMR from a functional and anatomical perspective.METHODS: In this review, we summarized previous studies investigating the effects of SMR which were associated with the human fascial system on flexibility, delayed onset of muscle soreness, arterial stiffness and autonomic nervous system (ANS).RESULTS: SMR with a foam roller can improve flexibility by increasing blood flow and circulation to the soft tissues. Foam rollingrelated mechanisms to increase range of motion or reduce pain include the activation of cutaneous and fascial mechanoreceptors and interstitial afferent nerves that modulate sympathetic/parasympathetic activation as well as the activation of global pain modulatory systems and reflex-induced reductions in muscle and myofascial tone. In addition, SMR with a foam roller may improve arterial stiffness, which was associated with increased circulating level of nitric oxide induced by elevated shear stress on the walls of the blood vessel.CONCLUSIONS: SMR using a foam roller improves flexibility by relaxing tension in skeletal muscles or fascia and may help to improve arterial stiffness and the function of the ANS. We suggest that SMR using a foam roller may help to reduce the risks of cardiovascular disease as a new alternative method.

[177Lu]Lu-DOTA-ZOL bone pain palliation in patients with skeletal metastases from various cancers: efficacy and safety results

Background [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy are limited. The objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods In total, 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR 8–14 months). The primary outcome endpoint was response assessment according to the visual analogue score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky performance status, overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results In total, 40 patients (15 males and 25 females) with a mean age of 46.6 ± 15.08 years (range 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal, and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty-eight patients died and the estimated median overall survival was 13 months (95% CI 10–14 months). A significant improvement was observed in the VAS, AS, and ECOG status when compared to baseline. None of the patients experienced grade III/IV haematological, kidney, or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3 - 2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8 - 14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24 - 78 years) were treated with either 1 (N=15) or 2 (N= 2lobal5) cycles of [177Lu]Lu-DOTA-ZOL. g According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10 - 14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers. Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3 - 2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8 - 14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global pain assessment score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0. Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24 - 78 years) were treated with either 1 (N=15) or 2 (N= 2lobal5) cycles of [177Lu]Lu-DOTA-ZOL. g According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10 - 14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy. Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.

Long term study on the effects of microsurgical DREZotomy for chronic pain control

The DREZotomy (Dorsal Root Entry Zone tomy) is an analgesic procedure. The analgesic effect is evaluated on 30 patients with chronic pain resulting from respectively: brachial plexus avulsion (66.6%), postherpetic pain (10%), hyperspastic states (6.6%), phantom pain (6.6%), the pain in the stump (6.6%), and spinal cord injuries (3.3%). Pain intensity was evaluated using a visual analogue scale (VAS). At last evaluation, between 12 and 60 months, after DREZotomy, 93% had a good or excellent global pain relief after surgery. According to the component types of pain, 9.6% of patients had good or excellent control of the paroxysmal pain, and 84% of the continuous pain. Kaplan–Meier prediction of lasting global pain control at 60 months of follow-up was calculated at 75.5%. Comparison of the 2 corresponding Kaplan–Meier curves at long term, namely, pain control in 82.8% for the paroxysmal component and in 51.7% for the continuous component, showed a statistically significant difference (P < 0.0001). Functional effects are improved by more than 70% according to patients.