Clinical Edge Journal Scan

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: The risk for hepatitis B virus (HBV) reactivation was substantially high in patients with rheumatoid arthritis (RA) and chronic HBV infection who were treated with anti-interleukin-6 (anti-IL-6), with the risk being ~5 times higher in the absence of antiviral prophylaxis.

Major finding: The HBV reactivation rate was 6.7% in patients with chronic HBV infection, with the value further increasing to 31% in patients without antiviral prophylaxis. In patients with resolved HBV infection, the HBV reactivation rate remained ~0% irrespective of antiviral prophylaxis administration.

Study details: This meta-analysis of 19 studies included 372 anti-IL-6-treated patients with RA who had chronic (n = 41) or resolved (n = 279) HBV infection, of whom 19 patients received antiviral prophylaxis.

Disclosures: This study did not receive any funding. Two authors declared receiving honoraria, speaker fees, or research grants from or participating in advisory boards of various sources.

Source: Katelani S et al. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: A systematic review and meta-analysis. Rheumatology (Oxford). 2023;62(SI3):SI252-SI259 (Oct 23). doi: 10.1093/rheumatology/kead243

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Compared with biological disease-modifying anti-rheumatic drugs (bDMARD), tofacitinib increased the risk for serious infections (SI) in older patients with rheumatoid arthritis (RA; age ≥ 69 years).

Major finding: The risk for non-fatal SI in the tofacitinib vs bDMARD treatment group was ~2 times higher in patients age 69 years (hazard ratio [HR] ~2.00; 95% CI ~1.02 to ~4.00) and ~2.8 times higher in those age ≥ 76 years (HR ~2.8; 95% CI 1.3 to ~6.4).

Study details: This observational cohort study included 1687 patients with RA enrolled in 2238 different treatment courses (TC), of which 345 and 1893 TC involved tofacitinib and bDMARD, respectively.

Disclosures: This study was supported by Pfizer. Several authors declared receiving speaker fees, consulting fees, research grants, or conference expenditures from or having other ties with various sources, including Pfizer.

Source: Riek M et al. Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care. Sci Rep. 2023;13:17776 (Oct 18). doi: 10.1038/s41598-023-44841-w

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: Tapering biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or both b/tsDMARD and conventional synthetic (cs) DMARD increased the risk for disease flares in patients with well-controlled rheumatoid arthritis (RA).

Major finding: Compared with patients whose medication was not tapered, the risk for flares was 31 times higher in the b/tsDMARD taper group (hazard ratio [HR] 31.43; P < .0001) and 18 times higher in the b/tsDMARD and csDMARD taper group (HR 18.45; P = .0039).

Study details: This 2-year prospective cohort study included 131 patients with RA who were on stable b/tsDMARD with or without csDMARD and achieved remission or low disease activity, of whom 39.7% underwent a DMARD taper.

Disclosures: This study was supported by the Autoimmune Association - Young Investigator Grant Award. The authors declared no conflicts of interest.

Source: Tageldin M et al. A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort. Rheumatology (Oxford). 2023;62(Suppl 4):iv8-iv13 (Oct 19). doi: 10.1093/rheumatology/kead430

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: In a vulnerable population of individuals with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKi), the herpes zoster subunit (HZ/su) vaccine elicited a serological immune response in most patients and had an acceptable safety profile.

Major finding: The geometric mean concentration of vaccine-specific antibody levels increased from 2317 ng/mL prevaccination to 26,916 ng/mL postvaccination (P < .0001) in patients with RA, with 80.5% of patients showing a ≥4-fold increase in antibody levels. After vaccination, only 6.5% of patients reported an increase in RA disease activity, and adverse events were mostly mild or moderate.

Study details: Findings are from a phase 4 trial including 82 patients with RA treated using JAKi and 51 control individuals without rheumatic diseases, all of whom received two doses of the HZ/su vaccine.

Disclosures: Two authors declared receiving support or research funds for the present study from various sources. T Bergström declared receiving payments or honoraria from GlaxoSmithKline. The other authors declared no conflicts of interest.

Source: Källmark H et al. Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors. Rheumatology (Oxford). 2023 (Oct 18). Doi: 10.1093/rheumatology/kead552.

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Compared with the general population, the risk for cancer was significantly higher in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARD).

Major finding: The all-cancer risk was 20% higher in patients with RA than in the general population (standardized incidence ratio [SIR] 1.20; 95% CI 1.17-1.23). The risk was particularly higher for solid cancers like bladder cancer (SIR 2.38; 95% CI 2.25-2.51), cervical cancer (SIR 1.80; 95% CI 1.62-2.01), and lung cancer (SIR 1.41; 95% CI 1.36-1.46) and for hematological malignancies like Hodgkin’s lymphoma (SIR 2.73; 95% CI 2.31-3.23).

Study details: This population-based observational study included 257,074 patients with RA and without a history of cancer, who received DMARD and were compared with the general population.

Disclosures: This study was supported by unrestricted grants from the French National Cancer Institute and the Assistance Publique des Hôpitaux de Paris. Four authors declared receiving research grants, consulting fees, or support for meetings or travel from various sources.

Source: Beydon M et al. Risk of cancer for patients with rheumatoid arthritis versus general population: A national claims database cohort study. Lancet Reg Health Eur. 2023;35:100768 (Oct 29). doi: 10.1016/j.lanepe.2023.100768

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Key clinical point: Janus kinase inhibitors (JAKi) like tofacitinib, baricitinib, peficitinib, and upadacitinib showed comparable efficacy, and all of these drugs had impressive remission rates in patients with rheumatoid arthritis (RA).

Major finding: At 6 months of treatment with JAKi, the average Clinical Disease Activity Index (CDAI) scores improved significantly (P < .001), with 1 out of 3 patients achieving CDAI-remission and ≥82% of patients achieving CDAI-low disease activity (LDA). The achievement rates of CDAI-remission and CDAI-LDA were comparable across the four treatment groups.

Study details: Findings are from analysis of a retrospective study including 361 patients with RA from the ANSWER cohort who received tofacitinib (n = 127), baricitinib (n = 153), peficitinib (n = 29), or upadacitinib (n = 52).

Disclosures: This study did not receive any specific funding. Some authors declared receiving research grants, payments for lectures, or speaking or consulting fees from various sources.

Source: Hayashi S et al. Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: The ANSWER cohort study. Rheumatology (Oxford). 2023 (Nov 1). doi: 10.1093/rheumatology/kead543

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.

The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.

There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: This real-world study confirms the efficacy and safety of erenumab in patients with migraine associated with extreme unmet needs.

Major finding: Overall, 52.9%, 58.5%, 57.0%, and 58.8% of patients receiving erenumab achieved ≥50% reduction in monthly migraine days at 3, 6, 9, and 12 months, respectively, with significant reductions in the proportion of patients with chronic migraine at all time points compared with baseline (P < .001). At month 3, 57.3% of patients changed from chronic migraine to episodic migraine. No treatment-related serious adverse events were reported.

Study details: Findings are from a 1-year prospective, real-word study including 140 patients with migraine and previous migraine preventive treatment failures who received ≥1 dose of erenumab.

Disclosures: This study did not receive funding from any source. Several authors declared receiving personal fees for consultancy activities or research support from various sources, and some authors declared no conflicts of interest.

Source: Lanteri-Minet M et al. One-year prospective real-world assessment of effectiveness and safety of erenumab in migraine prevention: Results of the French FHU INOVPAIN registry study. J Headache Pain. 2023;24:152 (Nov 8). doi: 10.1186/s10194-023-01680-4

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640

Key clinical point: Heavy secondhand smoke (SHS) exposure was positively associated with a higher risk for severe headaches or migraine in adults who never smoked.

Major finding: Heavy SHS exposure (serum cotinine level 1-10 ng/mL) was positively associated with severe headaches or migraine (adjusted odds ratio 2.02; P = .011). No significant association was observed between low SHS exposure (serum cotinine level 0.05-0.99 ng/mL) and headaches or migraine (P = .226).

Study details: This nationwide cross-sectional study included 4560 adults who had never smoked, of which 20% had severe headaches or migraine.

Disclosures: This study did not receive any funding from external sources. The authors declared no conflicts of interest.

Source: Wu J, Yang P, et al. Association between secondhand smoke exposure and severe headaches or migraine in never-smoking adults. Headache. 2023 (Nov 8). doi: 10.1111/head.14640

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781

Key clinical point: Patients with chronic migraine have autonomic dysfunction, the extent of which is evaluated using heart rate variability (HRV) analysis, and a preserved function is associated with a superior response to flunarizine preventive treatment.

Major finding: Most heart-rate variability (HRV) parameters, except the ratios of low-frequency (LF) band and LF/high-frequency band, were significantly lower in patients with migraine vs control individuals (P < .001). The response to flunarizine treatment was superior in patients with normal HRV, as exemplified by higher reductions in monthly headache days after 3 months in those with normal vs lower HRV (─9.7 days vs ─6.2 days; P = .026).

Study details: This cross-sectional, prospective study included 81 prophylaxis-naive patients with chronic migraine and 58 age- and gender-matched control individuals. Patients with migraine initiated flunarizine as a preventive treatment for 12 weeks.

Disclosures: This study was supported by grants from the National Science and Technology Council, Taiwan, and others. SJ Wang declared being a principal investigator and receiving personal fees as an advisor or speaker from various sources.

Source: Chuang CH et al. Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study. Cephalalgia. 2023 (Oct 18). doi: 10.1177/03331024231206781