Intrathecal Drug Delivery Effective for Cancer Pain
Although the safety and efficacy of intrathecal drug delivery systems (IDDS) have been demonstrated in small trials, the therapy remains underutilized for the management of cancer pain.
In 2003, a long-term multicenter international registry was started to monitor the performance of SynchroMed Infusion Systems. In 2013, patient-reported outcomes were added to this registry.
Through July 2017, 1403 patients with cancer pain were enrolled and implanted with an IDDS. Lung, breast, colon/rectal, pancreatic, and prostate were the most frequent types of cancer. Most patients (87%) were followed until death, whereas 4.3% exited due to device problems or therapy ending. Remaining patients were lost to follow-up or transfer of care. Pain scores in patients with baseline and follow-up data improved significantly at 6 (P = 0.0007) and 12 (P = 0.0026) months. Infection requiring surgical intervention was reported in 3.2% of patients.
The authors concluded that it is possible to attain not only adequate but improved pain control in patents with even advanced cancer. IDDS is a safe and effective option with a good benefit-risk ratio for these patients. (See Stearns LM, Abd-Elsayed A, Perruchoud C, et al. Intrathecal drug delivery systems for cancer pain analysis of a prospective, multicenter product surveillance registry [published online ahead of print September 18, 2019]. Anesth Analg. doi:10.1213/ANE.0000000000004425.)
Quitting Smoking May Not Improve Chronic Pain
Although smoking is associated with many adverse health effects, nicotine seems to have an acute antinociceptive effect, thought to be mediated through agonism of the nicotinic acetylcholine receptors (nAChRs), modulation of the descending pain-inhibitory pathway, and activation of the endogenous opioid system and neuroendocrine system. But, despite this potential analgesic effect, epidemiologic studies suggest that chronic tobacco use increases the risk of persistent pain.
Using the Collaborative Health Outcomes Information Registry (CHOIR) of patients attending the Stanford Pain Management Center from 2013-17, the authors conducted a propensity-weighed analysis of the independent effects of smoking on patients with chronic pain. A total of 12,368 patients completed the CHOIR questionnaire, of which 8584 patients had complete data for analysis. The study demonstrated that smokers had significantly worse outcomes compared with nonsmokers at both initial consultation and the first follow-up visit. Also, smokers tended to have worse pain interference, fatigue, sleep-related impairment, anger, emotional support, and depression over time compared with nonsmokers.
The authors suggest that smoking initiates a detrimental positive feedback cycle because pain prompts smoking behaviors and smoking increases pain over time. However, it is unclear whether smoking cessation among patients with chronic pain will improve outcomes. Acute nicotine withdrawal in habituated smokers can lead to negative somatic and affective symptoms, which could result in less coping and increased pain.
A randomized trial of veteran smokers with chronic illnesses (eg, diabetes, hypertension, and heart disease) demonstrated no difference in pain scores at 5 months in those who quit versus those who did not quit smoking. (See Khan JS, Hah JM, Mackey SC. Effects of smoking on patients with chronic pain: a propensity-weighted analysis on the Collaborative Health Outcomes Information Registry. Pain. 2019;160(10):2374-2379. doi:10.1097/j.pain.0000000000001631.)
Limited Efficacy of Corticosteroid Injection for Plantar Fasciitis
A systematic review and meta-analysis of randomized trials compared corticosteroid injection to comparators in patients with plantar fasciitis. Primary outcomes were pain and function, categorized as short (0-6 weeks), medium (7-12 weeks), or longer.
The authors included 47 trials (2989 participants) in their review. For pain reduction in the short term, corticosteroid injection was more effective than autologous blood injection and foot orthoses.
Findings in the medium term were not significant. In the longer term, corticosteroid injection was less effective than dry needling and platelet-rich plasma injection.
For improved function, corticosteroid injection was more effective than physical therapy in the short term. When trials considered to have high risk of bias were excluded, there were no significant findings.
The authors concluded that corticosteroid injection is more effective than some comparators for the reduction of pain and the improvement of function in people with plantar heel pain. However, corticosteroid injection is not more effective than placebo injection for reducing pain or improving function long term. (See Whittaker GA, Munteanu SE, Menz HB, et al. Corticosteroid injection for plantar heel pain: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2019;20(1):378. doi:10.1186/s12891-019-2749-z.)
Upadacitinib Superior in Rheumatoid Arthritis
JAK-1 has a major role in signaling of key proinflammatory cytokines. Upadacitinib is a JAK1-selective inhibitor that has been shown to reduce the pain and joint swelling of patients with rheumatoid arthritis. The authors compared it to placebo or adalimumab in patients with rheumatoid arthritis (RA) who were receiving methotrexate (MTX) but had an inadequate response.
A total of 1629 patients with RA who had a poor response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week). A stable background dose of MTX was continued. Primary end points included an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of less than 2.6 in the upadacitinib group, compared with the placebo group at week 12. Radiographic progression or lack thereof was evaluated at week 26. The study also tested efficacy of upadacitinib compared with adalimumab, as measured both clinically and functionally.
The study showed that, at week 12, both primary end points were met in patients receiving upadacitinib, compared with those receiving placebo (P <= 0.001).
An ACR20 improvement response was achieved by 71% of patients in the upadacitinib group when compared with 36% in the placebo group, and a DAS28-CRP score of less than 2.6 was observed in 29% of patients receiving upadacitinib compared with 6% of patients receiving placebo.
Based on the ACR50 response rate, achievement of a DAS28-CRP score of 3.2 or less, change in pain severity score, and change in the Health Assessment Questionnaire disability index upadacitinib was superior to adalimumab.
More patients receiving upadacitinib than those receiving placebo or adalimumab achieved low disease activity or remission (P <= 0.001) at week 26. Radiographic progression was significantly less in patients receiving upadacitinib than in placebo-treated patients (P <= 0.001).
By week 26, adverse events (AEs), including serious infections, were comparable between the upadacitinib and adalimumab groups. The proportions of patients with serious AEs and AEs leading to discontinuation were highest in the adalimumab group; the proportions of patients with herpes zoster and those with creatine phosphokinase (CPK) elevations were highest in the upadacitinib group.
Three malignancies, 5 major adverse cardiovascular events, and 4 deaths were reported among the groups, but none occurred in patients receiving upadacitinib. Six venous thromboembolic events were reported (1 in the placebo group, 2 in the upadacitinib group, and 3 in the adalimumab group).
The authors concluded that upadacitinib is superior to placebo and adalimumab for improving signs, symptoms, and physical function in patients with RA who are already receiving but not responsive to MTX. Also, radiographic progression was significantly inhibited by upadacitinib. Although upadacitinib inhibits the immune response, its overall safety profile was similar to that of adalimumab, except for higher rates of herpes zoster and CPK elevations. (See Fleischman R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase 111, double-blind randomised controlled trial [published online ahead of print July 9, 2019]. Arthritis Rheumatol. doi:10.1002/art.41032.)