Psoriatic Arthritis

Key clinical point: Patients with psoriasis who experienced nail pitting, musculoskeletal symptoms, or inflammation or had high body mass index (BMI) were at a higher risk of developing psoriatic arthritis (PsA).

Major finding: Patients with psoriasis who had arthralgia (pooled risk ratio [pRR] 2.15; 95% CI 1.16-3.99) or imaging-detected musculoskeletal inflammation or structural damage (pRR 3.72; 95% CI 2.12-6.51) were at a significantly higher risk for PsA. Other predictors of PsA included nail pitting (pooled hazard ratio [HR] 2.14; 95% CI 1.32-3.46) and higher BMI (adjusted HR 1.17; 95% CI 1.04-1.31).

Study details: Findings are from a meta-analysis of 16 cohort studies and 10 case-control studies including patients with skin/nail psoriasis without a diagnosis of PsA.

Disclosures: This study was partially funded by Novartis Farma, Italy. The authors declared no conflict of interests.

Source: Zabotti A et al. Rheumatol Ther. 2021 Oct 10. doi: 10.1007/s40744-021-00378-w.

Key clinical point: Patients with psoriasis who experienced nail pitting, musculoskeletal symptoms, or inflammation or had high body mass index (BMI) were at a higher risk of developing psoriatic arthritis (PsA).

Major finding: Patients with psoriasis who had arthralgia (pooled risk ratio [pRR] 2.15; 95% CI 1.16-3.99) or imaging-detected musculoskeletal inflammation or structural damage (pRR 3.72; 95% CI 2.12-6.51) were at a significantly higher risk for PsA. Other predictors of PsA included nail pitting (pooled hazard ratio [HR] 2.14; 95% CI 1.32-3.46) and higher BMI (adjusted HR 1.17; 95% CI 1.04-1.31).

Study details: Findings are from a meta-analysis of 16 cohort studies and 10 case-control studies including patients with skin/nail psoriasis without a diagnosis of PsA.

Disclosures: This study was partially funded by Novartis Farma, Italy. The authors declared no conflict of interests.

Source: Zabotti A et al. Rheumatol Ther. 2021 Oct 10. doi: 10.1007/s40744-021-00378-w.

Key clinical point: Patients with psoriasis who experienced nail pitting, musculoskeletal symptoms, or inflammation or had high body mass index (BMI) were at a higher risk of developing psoriatic arthritis (PsA).

Major finding: Patients with psoriasis who had arthralgia (pooled risk ratio [pRR] 2.15; 95% CI 1.16-3.99) or imaging-detected musculoskeletal inflammation or structural damage (pRR 3.72; 95% CI 2.12-6.51) were at a significantly higher risk for PsA. Other predictors of PsA included nail pitting (pooled hazard ratio [HR] 2.14; 95% CI 1.32-3.46) and higher BMI (adjusted HR 1.17; 95% CI 1.04-1.31).

Study details: Findings are from a meta-analysis of 16 cohort studies and 10 case-control studies including patients with skin/nail psoriasis without a diagnosis of PsA.

Disclosures: This study was partially funded by Novartis Farma, Italy. The authors declared no conflict of interests.

Source: Zabotti A et al. Rheumatol Ther. 2021 Oct 10. doi: 10.1007/s40744-021-00378-w.

Key clinical point: Almost 80% of the effect of tofacitinib treatment on health-related quality of life (HRQoL) is primarily mediated by improvement in itch and Physician’s Global Assessment of psoriasis (PGA-PsO).

Major finding: Overall, 82.3% of the effect of tofacitinib on HRQoL as measured by the Dermatology Life Quality Index was contributed by improvement in itch score (P < .0001) and 17.7% was attributed to improvement in PGA-PsO score (P = 0.0006).

Study details: Findings are from a post hoc analysis of phase 3 trials OPAL Broaden and OPAL Beyond including 468 patients with active psoriatic arthritis (PsA), randomly assigned to tofacitinib (5 mg or 10 mg twice a day), adalimumab 40 mg (only in OPAL Broaden), or placebo.

Disclosures: This study was funded by Pfizer. The authors declared receiving grants or serving as consultants for several pharmaceutical companies, including Pfizer. Four authors declared being employees and stockholders of Pfizer.

Source: Taylor PC et al. J Clin Med. 2021 (Sep 9);10(18):4081. doi: 10.3390/jcm10184081.

Key clinical point: Almost 80% of the effect of tofacitinib treatment on health-related quality of life (HRQoL) is primarily mediated by improvement in itch and Physician’s Global Assessment of psoriasis (PGA-PsO).

Major finding: Overall, 82.3% of the effect of tofacitinib on HRQoL as measured by the Dermatology Life Quality Index was contributed by improvement in itch score (P < .0001) and 17.7% was attributed to improvement in PGA-PsO score (P = 0.0006).

Study details: Findings are from a post hoc analysis of phase 3 trials OPAL Broaden and OPAL Beyond including 468 patients with active psoriatic arthritis (PsA), randomly assigned to tofacitinib (5 mg or 10 mg twice a day), adalimumab 40 mg (only in OPAL Broaden), or placebo.

Disclosures: This study was funded by Pfizer. The authors declared receiving grants or serving as consultants for several pharmaceutical companies, including Pfizer. Four authors declared being employees and stockholders of Pfizer.

Source: Taylor PC et al. J Clin Med. 2021 (Sep 9);10(18):4081. doi: 10.3390/jcm10184081.

Key clinical point: Almost 80% of the effect of tofacitinib treatment on health-related quality of life (HRQoL) is primarily mediated by improvement in itch and Physician’s Global Assessment of psoriasis (PGA-PsO).

Major finding: Overall, 82.3% of the effect of tofacitinib on HRQoL as measured by the Dermatology Life Quality Index was contributed by improvement in itch score (P < .0001) and 17.7% was attributed to improvement in PGA-PsO score (P = 0.0006).

Study details: Findings are from a post hoc analysis of phase 3 trials OPAL Broaden and OPAL Beyond including 468 patients with active psoriatic arthritis (PsA), randomly assigned to tofacitinib (5 mg or 10 mg twice a day), adalimumab 40 mg (only in OPAL Broaden), or placebo.

Disclosures: This study was funded by Pfizer. The authors declared receiving grants or serving as consultants for several pharmaceutical companies, including Pfizer. Four authors declared being employees and stockholders of Pfizer.

Source: Taylor PC et al. J Clin Med. 2021 (Sep 9);10(18):4081. doi: 10.3390/jcm10184081.

Key clinical point: Despite failing to achieve 20% or higher improvement in American College of Rheumatology (ACR20) criteria at week 104, some patients with psoriatic arthritis (PsA) receiving long-term treatment with apremilast experienced meaningful clinical benefits not completely captured by ACR20 response criteria.

Major finding: At week 104 of apremilast treatment, 58.0%, 41.7%, and 44.3% of patients who failed to achieve ACR20 had a mean improvement in swollen joint count, tender joint count, and Physician’s Global Assessment scores, respectively. Additionally, 33.8% and 68.2% of these patients achieved resolution of enthesitis and dactylitis.

Study details: Findings are pooled analysis of phase 3 studies, PALACE 1, 2, and 3, and included patients randomly assigned to 30 mg apremilast twice daily and classified into those who did not achieve (n = 109) and those who achieved (n = 193) ACR20 response at week 104.

Disclosures: This study was funded by Celgene. All investigators reported ties with various sources including Celgene.

Source: Mease PJ et al. Rheumatol Ther. 2021 Sep 18. doi: 10.1007/s40744-021-00369-x.

Key clinical point: Despite failing to achieve 20% or higher improvement in American College of Rheumatology (ACR20) criteria at week 104, some patients with psoriatic arthritis (PsA) receiving long-term treatment with apremilast experienced meaningful clinical benefits not completely captured by ACR20 response criteria.

Major finding: At week 104 of apremilast treatment, 58.0%, 41.7%, and 44.3% of patients who failed to achieve ACR20 had a mean improvement in swollen joint count, tender joint count, and Physician’s Global Assessment scores, respectively. Additionally, 33.8% and 68.2% of these patients achieved resolution of enthesitis and dactylitis.

Study details: Findings are pooled analysis of phase 3 studies, PALACE 1, 2, and 3, and included patients randomly assigned to 30 mg apremilast twice daily and classified into those who did not achieve (n = 109) and those who achieved (n = 193) ACR20 response at week 104.

Disclosures: This study was funded by Celgene. All investigators reported ties with various sources including Celgene.

Source: Mease PJ et al. Rheumatol Ther. 2021 Sep 18. doi: 10.1007/s40744-021-00369-x.

Key clinical point: Despite failing to achieve 20% or higher improvement in American College of Rheumatology (ACR20) criteria at week 104, some patients with psoriatic arthritis (PsA) receiving long-term treatment with apremilast experienced meaningful clinical benefits not completely captured by ACR20 response criteria.

Major finding: At week 104 of apremilast treatment, 58.0%, 41.7%, and 44.3% of patients who failed to achieve ACR20 had a mean improvement in swollen joint count, tender joint count, and Physician’s Global Assessment scores, respectively. Additionally, 33.8% and 68.2% of these patients achieved resolution of enthesitis and dactylitis.

Study details: Findings are pooled analysis of phase 3 studies, PALACE 1, 2, and 3, and included patients randomly assigned to 30 mg apremilast twice daily and classified into those who did not achieve (n = 109) and those who achieved (n = 193) ACR20 response at week 104.

Disclosures: This study was funded by Celgene. All investigators reported ties with various sources including Celgene.

Source: Mease PJ et al. Rheumatol Ther. 2021 Sep 18. doi: 10.1007/s40744-021-00369-x.

Key clinical point: Patients with psoriasis with the most severe disease were at highest risk of developing psoriatic arthritis (PsA), highlighting the need for regular screening for signs and symptoms of PsA.

Major finding: Overall incidence of PsA in patients with mild, moderate, and severe psoriasis was 2.1 (95% CI 2.1-2.1), 9.9 (95% CI 9.5-10.4), and 17.6 (95% CI 16.9-18.3) events per 100 patient-years, respectively. The 5-year prevalence rate of PsA was highest for patients with severe psoriasis (54.9%) and lowest for those with mild psoriasis (9.9%).

Study details: Findings are from a retrospective analysis of the United States Electronic Health Records database including 114,868 patients with newly diagnosed psoriasis.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The investigators reported ties with several sources including Novartis. Some of the investigators declared being current or former employees of Novartis Pharmaceuticals Corporation, Novartis Pharma AG, or KMK Consulting, Inc.

Source: Merola JF et al. J Am Acad Dermatol. 2021 Sep 18. doi: 10.1016/j.jaad.2021.09.019.

Key clinical point: Patients with psoriasis with the most severe disease were at highest risk of developing psoriatic arthritis (PsA), highlighting the need for regular screening for signs and symptoms of PsA.

Major finding: Overall incidence of PsA in patients with mild, moderate, and severe psoriasis was 2.1 (95% CI 2.1-2.1), 9.9 (95% CI 9.5-10.4), and 17.6 (95% CI 16.9-18.3) events per 100 patient-years, respectively. The 5-year prevalence rate of PsA was highest for patients with severe psoriasis (54.9%) and lowest for those with mild psoriasis (9.9%).

Study details: Findings are from a retrospective analysis of the United States Electronic Health Records database including 114,868 patients with newly diagnosed psoriasis.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The investigators reported ties with several sources including Novartis. Some of the investigators declared being current or former employees of Novartis Pharmaceuticals Corporation, Novartis Pharma AG, or KMK Consulting, Inc.

Source: Merola JF et al. J Am Acad Dermatol. 2021 Sep 18. doi: 10.1016/j.jaad.2021.09.019.

Key clinical point: Patients with psoriasis with the most severe disease were at highest risk of developing psoriatic arthritis (PsA), highlighting the need for regular screening for signs and symptoms of PsA.

Major finding: Overall incidence of PsA in patients with mild, moderate, and severe psoriasis was 2.1 (95% CI 2.1-2.1), 9.9 (95% CI 9.5-10.4), and 17.6 (95% CI 16.9-18.3) events per 100 patient-years, respectively. The 5-year prevalence rate of PsA was highest for patients with severe psoriasis (54.9%) and lowest for those with mild psoriasis (9.9%).

Study details: Findings are from a retrospective analysis of the United States Electronic Health Records database including 114,868 patients with newly diagnosed psoriasis.

Disclosures: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The investigators reported ties with several sources including Novartis. Some of the investigators declared being current or former employees of Novartis Pharmaceuticals Corporation, Novartis Pharma AG, or KMK Consulting, Inc.

Source: Merola JF et al. J Am Acad Dermatol. 2021 Sep 18. doi: 10.1016/j.jaad.2021.09.019.

Key clinical point: When choosing biologic medicines, patients with psoriatic arthritis (PsA) preferred oral medications and prioritized ability to work/lead a normal life and avoiding serious complications over clinical measures of improvement.

Major finding: Patients preferred oral vs. subcutaneous or intravenous routes (β coefficient 1.00; fixed parameter) and prioritized avoiding severe adverse events (β 0.72, 95% CI 0.50-0.95) and ability to attend normal activities (β 0.66; 95% CI 0.36-0.96) over improvement in enthesitis pain (β 0.28; 95% CI 0.20-0.36), psoriasis (β 0.28; 95% CI 0.20-0.36), and increasing chance of remission (β 0.27; 95% CI 0.19-0.36).

Study details: Findings are from a discrete choice experiment including 150 survey respondents with PsA, of which 75 patients were receiving biologics, 83 had an experience of biologic therapy, and 41 had an experience of 2 or more biologics.

Disclosures: The study had no funding to declare. Dr. Hassett declared receiving speaker fees or advisory board fees from AbbVie and Amgen.

Source: Sumpton D et al. Arthritis Care Res. 2021 Sep 13. doi: 10.1002/acr.24782.

Key clinical point: When choosing biologic medicines, patients with psoriatic arthritis (PsA) preferred oral medications and prioritized ability to work/lead a normal life and avoiding serious complications over clinical measures of improvement.

Major finding: Patients preferred oral vs. subcutaneous or intravenous routes (β coefficient 1.00; fixed parameter) and prioritized avoiding severe adverse events (β 0.72, 95% CI 0.50-0.95) and ability to attend normal activities (β 0.66; 95% CI 0.36-0.96) over improvement in enthesitis pain (β 0.28; 95% CI 0.20-0.36), psoriasis (β 0.28; 95% CI 0.20-0.36), and increasing chance of remission (β 0.27; 95% CI 0.19-0.36).

Study details: Findings are from a discrete choice experiment including 150 survey respondents with PsA, of which 75 patients were receiving biologics, 83 had an experience of biologic therapy, and 41 had an experience of 2 or more biologics.

Disclosures: The study had no funding to declare. Dr. Hassett declared receiving speaker fees or advisory board fees from AbbVie and Amgen.

Source: Sumpton D et al. Arthritis Care Res. 2021 Sep 13. doi: 10.1002/acr.24782.

Key clinical point: When choosing biologic medicines, patients with psoriatic arthritis (PsA) preferred oral medications and prioritized ability to work/lead a normal life and avoiding serious complications over clinical measures of improvement.

Major finding: Patients preferred oral vs. subcutaneous or intravenous routes (β coefficient 1.00; fixed parameter) and prioritized avoiding severe adverse events (β 0.72, 95% CI 0.50-0.95) and ability to attend normal activities (β 0.66; 95% CI 0.36-0.96) over improvement in enthesitis pain (β 0.28; 95% CI 0.20-0.36), psoriasis (β 0.28; 95% CI 0.20-0.36), and increasing chance of remission (β 0.27; 95% CI 0.19-0.36).

Study details: Findings are from a discrete choice experiment including 150 survey respondents with PsA, of which 75 patients were receiving biologics, 83 had an experience of biologic therapy, and 41 had an experience of 2 or more biologics.

Disclosures: The study had no funding to declare. Dr. Hassett declared receiving speaker fees or advisory board fees from AbbVie and Amgen.

Source: Sumpton D et al. Arthritis Care Res. 2021 Sep 13. doi: 10.1002/acr.24782.

Key clinical point: Evaluation with power Doppler ultrasound revealed a rapid and significant reduction of synovitis in patients with psoriatic arthritis (PsA) upon treatment with secukinumab.

Major finding: At week 12, the adjusted mean change in the global European League Against Rheumatism (EULAR) and the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) (EULAR-OMERACT) synovitis score was significantly higher in secukinumab vs. placebo group (−9 vs. −6; difference −3; P = .004), with the effect of secukinumab evident as early as week 1 of treatment initiation. The incidence of treatment-emergent adverse events in secukinumab vs. placebo group was 58% vs. 57%.

Study details: Findings are 12-week results from ULTIMATE, a phase 3 study including 166 biologic-naive patients with concomitant PsA and synovitis who failed conventional synthetic disease-modifying antirheumatic drugs. Patients were randomly assigned to receive subcutaneous secukinumab (300 mg or 150 mg) or placebo weekly until week 4, followed by 4-weekly dosing until week 52.

Disclosures: This study was funded by Novartis. Some of the authors reported ties with various sources including Novartis. A Duggan, P Goyanka, and C Gaillez declared being employees of or owning stock in Novartis.

Source: D'Agostino MA et al. Rheumatology. 2021 Sep 16. doi: 10.1093/rheumatology/keab628.

Key clinical point: Evaluation with power Doppler ultrasound revealed a rapid and significant reduction of synovitis in patients with psoriatic arthritis (PsA) upon treatment with secukinumab.

Major finding: At week 12, the adjusted mean change in the global European League Against Rheumatism (EULAR) and the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) (EULAR-OMERACT) synovitis score was significantly higher in secukinumab vs. placebo group (−9 vs. −6; difference −3; P = .004), with the effect of secukinumab evident as early as week 1 of treatment initiation. The incidence of treatment-emergent adverse events in secukinumab vs. placebo group was 58% vs. 57%.

Study details: Findings are 12-week results from ULTIMATE, a phase 3 study including 166 biologic-naive patients with concomitant PsA and synovitis who failed conventional synthetic disease-modifying antirheumatic drugs. Patients were randomly assigned to receive subcutaneous secukinumab (300 mg or 150 mg) or placebo weekly until week 4, followed by 4-weekly dosing until week 52.

Disclosures: This study was funded by Novartis. Some of the authors reported ties with various sources including Novartis. A Duggan, P Goyanka, and C Gaillez declared being employees of or owning stock in Novartis.

Source: D'Agostino MA et al. Rheumatology. 2021 Sep 16. doi: 10.1093/rheumatology/keab628.

Key clinical point: Evaluation with power Doppler ultrasound revealed a rapid and significant reduction of synovitis in patients with psoriatic arthritis (PsA) upon treatment with secukinumab.

Major finding: At week 12, the adjusted mean change in the global European League Against Rheumatism (EULAR) and the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) (EULAR-OMERACT) synovitis score was significantly higher in secukinumab vs. placebo group (−9 vs. −6; difference −3; P = .004), with the effect of secukinumab evident as early as week 1 of treatment initiation. The incidence of treatment-emergent adverse events in secukinumab vs. placebo group was 58% vs. 57%.

Study details: Findings are 12-week results from ULTIMATE, a phase 3 study including 166 biologic-naive patients with concomitant PsA and synovitis who failed conventional synthetic disease-modifying antirheumatic drugs. Patients were randomly assigned to receive subcutaneous secukinumab (300 mg or 150 mg) or placebo weekly until week 4, followed by 4-weekly dosing until week 52.

Disclosures: This study was funded by Novartis. Some of the authors reported ties with various sources including Novartis. A Duggan, P Goyanka, and C Gaillez declared being employees of or owning stock in Novartis.

Source: D'Agostino MA et al. Rheumatology. 2021 Sep 16. doi: 10.1093/rheumatology/keab628.

Key clinical point: Patients with psoriasis who initiated biologics were more likely to develop psoriatic arthritis (PsA) than those who initiated phototherapy or oral therapy.

Major finding: The incidence rate of PsA regardless of exposure to any treatment was 9.75 per 1000 person-years vs. 77.26, 61.99, and 26.11 per 1000 person-years among initiators of biologics, oral therapy, and phototherapy, respectively. Patients receiving biologics were at a significantly higher risk of developing PsA vs. those receiving either oral or phototherapy (hazard ratio 4.48; 95% CI 4.23-4.75).

Study details: Findings are from a retrospective cohort study including 193,709 patients with psoriasis without PsA, of which 14,569 biologic and 20,321 cumulative oral and phototherapy initiations were identified.

Disclosures: R Fitzsimmons and A Ogdie received funding from National Psoriasis Foundation. Dr. Gelfand, T Love, and A Ogdie reported ties with several sources.

Source: Meer E et al. Ann Rheum Dis. 2021 Oct 6. doi: 10.1136/annrheumdis-2021-220761.

Key clinical point: Patients with psoriasis who initiated biologics were more likely to develop psoriatic arthritis (PsA) than those who initiated phototherapy or oral therapy.

Major finding: The incidence rate of PsA regardless of exposure to any treatment was 9.75 per 1000 person-years vs. 77.26, 61.99, and 26.11 per 1000 person-years among initiators of biologics, oral therapy, and phototherapy, respectively. Patients receiving biologics were at a significantly higher risk of developing PsA vs. those receiving either oral or phototherapy (hazard ratio 4.48; 95% CI 4.23-4.75).

Study details: Findings are from a retrospective cohort study including 193,709 patients with psoriasis without PsA, of which 14,569 biologic and 20,321 cumulative oral and phototherapy initiations were identified.

Disclosures: R Fitzsimmons and A Ogdie received funding from National Psoriasis Foundation. Dr. Gelfand, T Love, and A Ogdie reported ties with several sources.

Source: Meer E et al. Ann Rheum Dis. 2021 Oct 6. doi: 10.1136/annrheumdis-2021-220761.

Key clinical point: Patients with psoriasis who initiated biologics were more likely to develop psoriatic arthritis (PsA) than those who initiated phototherapy or oral therapy.

Major finding: The incidence rate of PsA regardless of exposure to any treatment was 9.75 per 1000 person-years vs. 77.26, 61.99, and 26.11 per 1000 person-years among initiators of biologics, oral therapy, and phototherapy, respectively. Patients receiving biologics were at a significantly higher risk of developing PsA vs. those receiving either oral or phototherapy (hazard ratio 4.48; 95% CI 4.23-4.75).

Study details: Findings are from a retrospective cohort study including 193,709 patients with psoriasis without PsA, of which 14,569 biologic and 20,321 cumulative oral and phototherapy initiations were identified.

Disclosures: R Fitzsimmons and A Ogdie received funding from National Psoriasis Foundation. Dr. Gelfand, T Love, and A Ogdie reported ties with several sources.

Source: Meer E et al. Ann Rheum Dis. 2021 Oct 6. doi: 10.1136/annrheumdis-2021-220761.

Key clinical point: Disease activity-guided dose optimization (DAGDO) of tumor necrosis factor inhibitor (TNFi) showed no negative effect on disease activity in patients with psoriatic arthritis (PsA).

Major finding: Compared with the full-dose continuation period, the mean disease activity score in 28-joint count C-reactive protein was not significantly different for DAGDO (0.06; P = .44) and stable dose after DAGDO (0.03; P = .72) periods. Moreover, the rate ratio of infections was not different in DAGDO (0.76; P = .57) and stable dose after DAGDO (0.77; P = .60) periods compared to the full-dose continuation period.

Study details: Findings are from 2 controlled, parallel, retrospective cohorts including 153 patients with PsA and 171 patients with axial spondyloarthritis who were doing well taking TNFi and were eligible for DAGDO.

Disclosures: This study did not report any source of funding. Dr. den Broeder A declared receiving consultancy, honoraria, congress invitations, and research grants from various sources.

Source: Michielsens CAJ et al. Rheumatology. 2021 Oct 2. doi: 10.1093/rheumatology/keab741.

Key clinical point: Disease activity-guided dose optimization (DAGDO) of tumor necrosis factor inhibitor (TNFi) showed no negative effect on disease activity in patients with psoriatic arthritis (PsA).

Major finding: Compared with the full-dose continuation period, the mean disease activity score in 28-joint count C-reactive protein was not significantly different for DAGDO (0.06; P = .44) and stable dose after DAGDO (0.03; P = .72) periods. Moreover, the rate ratio of infections was not different in DAGDO (0.76; P = .57) and stable dose after DAGDO (0.77; P = .60) periods compared to the full-dose continuation period.

Study details: Findings are from 2 controlled, parallel, retrospective cohorts including 153 patients with PsA and 171 patients with axial spondyloarthritis who were doing well taking TNFi and were eligible for DAGDO.

Disclosures: This study did not report any source of funding. Dr. den Broeder A declared receiving consultancy, honoraria, congress invitations, and research grants from various sources.

Source: Michielsens CAJ et al. Rheumatology. 2021 Oct 2. doi: 10.1093/rheumatology/keab741.

Key clinical point: Disease activity-guided dose optimization (DAGDO) of tumor necrosis factor inhibitor (TNFi) showed no negative effect on disease activity in patients with psoriatic arthritis (PsA).

Major finding: Compared with the full-dose continuation period, the mean disease activity score in 28-joint count C-reactive protein was not significantly different for DAGDO (0.06; P = .44) and stable dose after DAGDO (0.03; P = .72) periods. Moreover, the rate ratio of infections was not different in DAGDO (0.76; P = .57) and stable dose after DAGDO (0.77; P = .60) periods compared to the full-dose continuation period.

Study details: Findings are from 2 controlled, parallel, retrospective cohorts including 153 patients with PsA and 171 patients with axial spondyloarthritis who were doing well taking TNFi and were eligible for DAGDO.

Disclosures: This study did not report any source of funding. Dr. den Broeder A declared receiving consultancy, honoraria, congress invitations, and research grants from various sources.

Source: Michielsens CAJ et al. Rheumatology. 2021 Oct 2. doi: 10.1093/rheumatology/keab741.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

Among patients with immune-mediated inflammatory diseases (IMIDs) who get COVID-19, the risk for hospitalization and death is lower if they are receiving tumor necrosis factor (TNF) inhibitor monotherapy, compared with receiving most other common drugs for these conditions, with or without TNF inhibitors, according to a study published in JAMA Network Open The only combination not associated with an increased risk for hospitalization or death was TNF inhibitor therapy with methotrexate.

“These findings support the continued use of TNF inhibitor monotherapy during the pandemic and warrant further research investigating the association of other biologic therapies with COVID-19 outcomes,” write Zara Izadi, MPharm, of the University of California, San Francisco, and her colleagues. “Treatment with TNF inhibitor combination therapy was associated with a more favorable safety profile when methotrexate rather than azathioprine/6-mercaptopurine was used, suggesting that clinicians would benefit from weighing the risks versus benefits of deescalating treatment or changing medications when a patient is receiving concomitant TNF inhibitors and azathioprine/6-mercaptopurine,” they write.
 

Findings mirror those seen in other settings

These findings are in line with what has been found in other settings, according to Joel M. Gelfand, MD, director of the psoriasis and phototherapy treatment center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, Philadelphia.

“In the beginning of the pandemic, there was concern about use of immune-modulating treatments, and many patients self-discontinued treatments like TNF inhibitors,” Dr. Gelfand, who was not involved in the study, told this news organization. “This has ultimately proved unnecessary and unfortunately resulted in harm to many patients due to flaring of their underlying disease.”

Dr. Gelfand emphasized the importance of vaccinating patients against COVID-19 as soon as possible and of getting a third dose for those who are already fully vaccinated with the Pfizer or Moderna shots, as recommended by the Centers for Disease Control and Prevention.

“I typically recommend this third dose be taken 6 months after the second dose,” Dr. Gelfand said. “The good news is that TNF inhibitors do not seem to meaningfully impact response to mRNA vaccines.”
 

Study details

The researchers analyzed data from three international registries of adults with rheumatic diseases, inflammatory bowel disease, and psoriasis who had COVID-19 between March 12, 2020, and Feb. 1, 2021. The registries included the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, the Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect), and the physician-reported registry from the Global Rheumatology Alliance (GRA).

The population included 6,077 patients from 74 countries. About half of the cohort (52.9%) were from Europe; more than half were women (58.6%). The average age was 48 years. A little over one-third of the patients (35.3%) had rheumatoid arthritis, 25.3% had Crohn’s disease, 12.5% had ulcerative colitis, 10.3% had spondyloarthritis, and 9.3% had psoriatic arthritis. Smaller percentages had psoriasis (4.9%), another type of arthritis or multiple types (1.7%), or another inflammatory bowel disease (0.6%).

One in five patients (21.3%) were hospitalized, and 3.1% died. The researchers compared outcomes for those who were receiving TNF inhibitor therapy alone to outcomes for those who were taking azathioprine/6-mercaptopurine therapy (alone or with a TNF inhibitor), methotrexate (alone or with a TNF inhibitor), and Janus kinase (JAK) inhibitors. They adjusted their analysis to account for active disease and common comorbidities, as well as geography and the period during the pandemic in which the person was admitted, because treatment regimens and hospitalization indications have varied over time.

All of the therapies except the combination of TNF inhibitors and methotrexate were associated with higher odds of hospitalization and death than TNF inhibitor monotherapy.

The researchers explored several possible explanations for the findings, including the possibility that high serum TNF concentrations may have been associated with more organ damage at the time of COVID-19 admission, owing to interaction with SARS-CoV-2–associated hyperinflammation.

“Therefore, blocking TNF could inhibit this detrimental immune response,” the authors write. “Multiple case series reporting favorable outcomes among patients receiving TNF inhibitor therapy support this assertion.”

Another possibility relates to the effects of taking non–TNF inhibitor medications for immunosuppression. The authors note that thiopurine medications are linked to a greater risk for opportunistic viral infections and that JAK inhibitors may reduce the body’s ability to clear the virus because of its suppression of innate immune response.

The authors also postulate that methotrexate may lower the likelihood of cytokine storm linked to COVID-19, even though methotrexate monotherapy was associated with poorer outcomes. “This association could mean that TNF inhibitor therapy is exerting a protective benefit or that methotrexate therapy is exerting a harmful consequence,” the authors write.

 

Caution needed in interpreting uncontrolled, registry-based data

The findings were not surprising to Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University, Chicago, who was not involved in the research.

Northwestern University

“We’ve been monitoring IBD [inflammatory bowel disease] patients through the Secure registry similar to the rheumatologic and dermatologic societies and have not identified a signal of harm from any international groups,” Dr. Hanauer told this news organization. He noted that these registries also have not shown an increased risk for COVID-19 complications among patients receiving TNF inhibitors, antiadhesion therapies, or anti–IL12/23 inhibitors, compared with the general population not taking these therapies.

The study’s size and the diversity of patients strengthen its findings. However, the registries’ use of convenience sampling increases the potential for reporting bias, although the results remained similar after a sensitivity analysis. The study also lacked a control group, and the registries did not collect data uniformly.

“These are databases that rely on reporting from investigators and are not comprehensive prospective studies,” Dr. Hanauer noted as another study limitation.

Dr. Gelfand similarly advised caution in interpreting these findings, inasmuch as the study is a “collection of spontaneous reports” that should be viewed as hypothesis-generating rather than testing.

“Fortunately, more rigorous studies have been conducted, typically in large medical record systems, and have confirmed the hypothesis that TNF inhibitors are associated with a lower risk of poor COVID-19 outcomes, compared to other treatments,” Dr. Gelfand said.

Previous smaller studies similarly found better outcomes among patients taking TNF inhibitors, compared with other therapies, but their participants were predominantly from North America and Europe, noted Licio A. Velloso, MD, PhD, of the University of Campinas, in São Paulo, in an accompanying commentary.

On the basis of the findings of this study, “which included a much larger sample comprising distinct diseases and patients with a multitude of genetic backgrounds, the evidence in favor of the continued use of TNF inhibitor monotherapy for patients with IMIDs during the COVID-19 pandemic has become more substantial,” Dr. Velloso writes. “The finding that maintenance of TNF inhibitor monotherapy is associated with reductions in the risk of severe COVID-19 among patients with IMIDs offers new perspective that may guide health care professionals in the difficult decisions regarding therapeutic approaches among this specific group of patients.”

The research was funded by the American College of Rheumatology, the European Alliance of Associations for Rheumatology, the United Kingdom’s National Institute for Health Research Biomedical Research Center, and the Psoriasis Association. Many authors reported receiving grants and/or personal fees from a variety of pharmaceutical companies. Dr. Velloso has disclosed no relevant financial relationships. Dr. Hanauer has served as a consultant to companies that market TNF inhibitors. Dr. Gelfand has consulted for and received research grants from companies that market TNF inhibitors.

A version of this article first appeared on Medscape.com.

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

A version of this article first appeared on Medscape.com.

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

A version of this article first appeared on Medscape.com.

Tramadol is increasingly used to manage chronic noncancer pain, but as compared with opioids, it appears to be linked to a higher risk for adverse outcomes, according to new data.

Among a cohort of patients who received a prescription for either tramadol or codeine for orthopedic-related pain, tramadol was significantly associated with a higher risk of mortality, cardiovascular events, and fractures.

However, there was no significant difference in the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders between the two drugs.

“However, this is a retrospective cohort study, and despite it providing information that would otherwise be impossible to gather – such as from randomized controlled trials – clinicians should not solely base their decision on this study,” cautioned lead author Carlen Reyes, MD, PhD, of the Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol), Barcelona.

Dr. Reyes noted that the intake of tramadol and codeine was analyzed using the number of “packages” that were dispensed, as an approximation of the real intake. “Logically we could think that the more packages dispensed of one drug, the more dose the patient is taking, but this is not always true given the availability of different doses commercialized of tramadol and different doses prescribed,” she said. “Given that we did not account for the real dose prescribed, we can only suspect an increased risk of these outcomes and reinforce the need for further prospective studies with more specific dose-response analysis comparing tramadol and codeine.”

The paper was published Oct. 19 in JAMA.

Tramadol has been considered to be a relatively safe opioid and was even strongly recommended by the American Academy of Orthopaedic Surgeons for patients experiencing symptomatic knee osteoarthritis. The authors point out that studies looking at opioid use from 2019 to 2020 show that tramadol was the most prescribed opioid in England, the Netherlands, and Spain.

In the United States, the age-adjusted rate of drug overdose deaths from synthetic opioids rose from 1.0 per 100 000 in 2013 to 11.4 in 2019. Most of these deaths were attributable to fentanyl but some were also related to tramadol.

But despite its wide use in managing chronic noncancer pain, results of recent studies suggest adverse outcomes as compared with other agents. Last year, one study found that older patients who received tramadol had a significant increase in the risk of hip fracture vs. those using NSAIDs or codeine. Another study, also published in 2020, showed that patients with osteoarthritis who were treated with tramadol had a 20%-50% higher risk of dying during the first year of treatment than did patients who were treated with NSAIDs.

In the current paper, Dr. Reyes and colleagues evaluated the association of tramadol with mortality and other adverse clinical outcomes in outpatient settings, compared with codeine.

They conducted a retrospective, population-based, propensity score–matched cohort study using a primary care database that routinely collects medical records and pharmacy dispensations for more than 80% of the population of Catalonia, Spain. The cohort included people 18 years or older who had been prescribed tramadol or codeine from 2007 to 2017 and were followed up to Dec. 31, 2017.

After propensity score matching, the final analysis included 368,960 participants: 184,480 in the tramadol arm and 184,480 in the codeine arm.

The mean age of patients was 52.7 years in the tramadol arm and 53.5 years in the codeine arm, and the prevalence of cancer was 3.2% and 3.3%, respectively. The most common diagnoses in this cohort were back pain (47.5% vs. 48.5%), neck/shoulder pain (28.6% vs. 29.5%), and osteoarthritis (15.3% vs. 15.5%). The most commonly used drugs were ibuprofen (34.4% vs. 34.3%) and paracetamol/acetaminophen (37.1% vs. 36.8%)

Higher risk of adverse outcomes

As compared with codeine, tramadol use was significantly associated with a higher risk of mortality (13.00 vs. 5.61 per 1,000 person-years; hazard ratio, 2.31; 95% confidence interval, 2.08-2.56); absolute rate differences (7.37 per 1,000 person-years; 95% CI, 6.09-8.78), cardiovascular events (10.03 vs. 8.67 per 1,000 person-years; HR, 1.15; 95% CI, 1.05-1.27; ARD, 1.36 per 1,000 person-years; 95% CI, 0.45-2.36), and fractures (12.26 vs. 8.13 per 1,000 person-years; HR, 1.50; 95% CI, 1.37-1.65; ARD, 4.10 per 1,000 person-years; 95% CI, 3.02-5.29).

A subgroup and sensitivity analysis showed that the increased mortality risk associated with tramadol was significantly higher in younger persons vs. older ones (HR, 3.14; 95% CI, 1.82-5.41 vs. 2.39; 95% CI, 2.20-2.60]; P < .001 for interaction). In addition, women had a significantly greater risk of cardiovascular events versus men (HR, 1.32; 95% CI, 1.19-1.46] vs. 1.03; 95% CI, 0.9-1.13]; P < .001 for interaction).
 

Potential for confounding

Weighing in on the data, Daniel Solomon, MD, MPH, chief of clinical sciences, division of rheumatology, Brigham and Women’s Hospital, and professor of medicine, Harvard Medical School, Boston, noted that because it is extremely unlikely that anyone will ever conduct a large, head-to-head safety trial comparing different opioids, the results of this paper are important to consider.

“However, as the authors appropriately caution, this type of analysis is limited by the strong potential for residual confounding,” he said. “In other words, even though the authors used state-of-the-art methods to limit imbalances between the patients initiating tramadol versus codeine, there is strong reason to believe that imbalances that may account for the differences in adverse events exist.”

For example, he noted that if one looks at the distribution of comorbid conditions in the before-matching group, tramadol initiators demonstrate a higher frequency of chronic kidney disease, diabetes, and overall chronic comorbid diseases. “This suggests to me that prescribers apply selection criteria when choosing who to prescribe which opioid,” Dr. Solomon explained.

“While the authors’ use of propensity score matching limits confounding, it only can improve balance for measured confounders,” he said. “Other factors not measured in this type of data set – blood pressure, pain, physical activity, tobacco use, body mass index – may still demonstrate imbalances even after matching.”

But after these limitations are taken into consideration, the results remain concerning, Dr. Solomon emphasized, particularly the all-cause mortality excess of tramadol versus codeine users. “This study did not include cause of death, which would help the reader understand why users of tramadol were dying more frequently,” he added. “It also might help in understanding whether this is a true biologic effect or residual confounding.”

Perceived safety

In an accompanying editorial, Howard S. Kim, MD, MS, and colleagues from Northwestern University, Chicago, write that the greatest risk of tramadol may involve the perception that it is “inherently safer than other opioids.”

“In actuality, the mechanisms of action and variable metabolism of tramadol in a given population create considerable therapeutic uncertainty and introduce additional risk exposure,” they say, as demonstrated in the current study.

Therefore, when clinicians determine that an opioid is needed for pain relief, it may be a better option to select a pure opioid agonist that has a more predictable therapeutic effect and known adverse effect profile, such as morphine or hydrocodone. “This would allow clinicians and patients to more properly weigh the risks and benefits of initiating opioid therapy through shared decision-making and prompt the level of counseling on safe use, storage, and disposal practices that all opioids deserve,” write the editorialists.

The study was funded by the Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Reyes has disclosed no relevant financial relationships. Dr. Solomon disclosed salary support from research contracts to his hospital from Amgen, AbbVie, Moderna, the Rheumatology Research Foundation, and National Institutes of Health; and royalties from UpToDate. Dr. Kim reported unrelated grant support from the Agency for Healthcare Research and Quality.
 

A version of this article first appeared on Medscape.com.