MDedge Rheumatology

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

Key clinical point: Rheumatoid arthritis (RA) increased the prevalence of interstitial lung abnormalities (ILA) in participants with a history of smoking, which in turn led to a significant increase in the mortality rate.

Major finding: ILA were ~4 times more prevalent in individuals with a history of smoking who did vs did not have RA (adjusted odds ratio 4.15; 95% CI 2.17-7.97). Among patients with RA and a record of smoking, mortality risk was ~3 times higher in those with ILA or indeterminate ILA findings vs those without ILA (adjusted hazard ratio 2.86; 95% CI 1.33-6.16).

Study details: This cross-sectional prospective study included participants with a current or past history of smoking from the COPDGene cohort, of whom 83 participants had RA and were compared with 8725 individuals without RA.

Disclosures: COPDGene was supported by the US National Heart, Lung, and Blood Institute and others. Several authors declared receiving consulting fees, grant support, research support, or having other ties with various sources.

Source: McDermott GC et al. Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers. Rheumatology (Oxford). 2023;62(SI3):SI286-SI295 (Oct 23). doi: 10.1093/rheumatology/kead277

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

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of low-dose methotrexate among older adults with chronic kidney disease (CKD) was associated with a significantly increased risk at 90 days for serious adverse events requiring a hospital visit, compared with starting treatment with hydroxychloroquine.

METHODOLOGY:

• In a retrospective, population-based cohort study conducted in Ontario, researchers used linked administrative healthcare data to identify adults aged 66 years and older with CKD who were not undergoing dialysis and were new to medication; CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m².
• The study population included 2,309 individuals who began treatment with low-dose methotrexate (5-35 mg/week); they were matched with 2,309 individuals who began treatment with hydroxychloroquine (200-400 mg/day). The median age was 76 years, 69% were women, and rheumatoid arthritis was the most common diagnosis (56%).
• The primary outcome was the risk of a hospital visit at 90 days for a composite of serious adverse events that included myelosuppression, sepsis, pneumotoxic effects, or hepatoxic effects.

TAKEAWAY:

• Overall, 3.55% of methotrexate patients and 1.73% of hydroxychloroquine patients met the primary outcome (risk ratio, 2.05); these events occurred at a median of 49 days and 43 days after starting the medications for the two groups, respectively.
• In an analysis by eGFR category, the risk of serious adverse events at 90 days increased among patients with eGFR levels less than 45 mL/min per 1.73 m² (RR, 2.79).
• In a secondary comparison, the 90-day risk of serious adverse events was higher among methotrexate patients who began treatment with doses of 15-35 mg/week in comparison with those whose initial doses were 5 to less than 15 mg/week.

IN PRACTICE:

“Patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects,” the researchers wrote.

SOURCE:

The lead author on the study was Flory T. Muanda, MD, of Western University, London, Ont. The study was published online in JAMA Network Open.

LIMITATIONS:

The observational design and lack of data on patients’ adherence to medications were among the limiting factors, as were the focus on older adults with CKD and the lack of assessment of the risk-benefit ratio of low-dose methotrexate.

DISCLOSURES:

The study was supported by the Institute for Clinical Evaluative Sciences. Dr. Muanda had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

NEW YORK – From clinical trials to textbooks, patients with darker skin types who have psoriasis overall – and Black patients in particular – are underrepresented, which might at least partially explain why clinicians are slow to recognize nail involvement, even when the skin disease has already been diagnosed, according to Shari R. Lipner, MD.

In a recently published review of 45 randomized controlled trials of therapies for nail psoriasis, almost all included information about the gender of the patients enrolled, but only about 35% reported race and/or ethnicity, Dr. Lipner, associate professor of dermatology, Weill Cornell Medical College, New York, said at the Skin of Color Update 2023. The proportion climbed to 59% in trials that included at least one study site in the United States, although representation of non-White patients in studies conducted in the United States was not proportional to the population (13.4% vs. 39.9%), said Dr. Lipner, senior author of the review .
 

Black patients largely unrepresented in photos

When an Internet search was conducted for images of nail psoriasis, the proportion of images fell as the number of the Fitzpatrick scale increased. Fitzpatrick skin types 1 or 2 represented 70% of the images, skin types 3 to 4 represented about 27%, leaving just 3% represented by darker skin types, Dr. Lipner said.

Ted Bosworth/MDedge News

“Unfortunately, things are not much better if you look at the dermatology and nail-specific textbooks. In fact, the percentages we see are almost identical,” said Dr. Lipner, noting that her review of images suggested that only about 3% of images in textbooks are of Fitzpatrick skin types 5 or 6, an obstacle for clinicians learning to recognize nail involvement in skin of color patients with psoriasis.

“We have written a couple of papers on this topic, including a call to action” in a letter to the editor in the Journal of the American Academy of Dermatology, Dr. Lipner noted. “To ensure access to safe and effective treatments for all patient populations,” she and her coauthor wrote, “we advocate the prioritized enrollment of racial and ethnic minority groups in psoriasis, PsA [psoriatic arthritis], and NP [nail psoriasis] clinical trials.”

Data from the 2009-2010 U.S. National Health and Nutrition Examination Survey (NHANES) confirms that psoriasis is less common in Blacks (1.9%) and Hispanics (1.6%) than Whites (3.6%). But these lower numbers still translate into substantial numbers nationally. Of those with psoriasis, the lifetime incidence of nail involvement has been variously estimated between 80% and 90%, Dr. Lipner said.

In about 10% of patients with psoriasis, nail involvement is isolated, occurring in the absence of skin lesions, a proportion that appears to be similar in Blacks and Whites according to Dr. Lipner.
 

Patient characteristics similar by race

In a study conducted at her own center, many of the characteristics of psoriasis were similar when those with a Fitzpatrick skin type 4 or higher were compared to those of 3 or lower. This included male-female distribution, smoking history, and presence of accompanying psoriatic arthritis. There was one discrepancy between lighter and darker skin.

“The big difference was that it took almost 3 years longer [on average] for darker skin to be diagnosed, and there was worse severity of disease,” Dr. Lipner said.

Like cutaneous manifestations of psoriasis, there are differences in appearance in the nail, many of which are simply produced by how skin color alters the appearance, such as the brownish hue of erythema in darker versus lighter skin. Dr. Lipner also noted that many of the features, such as keratosis, can be more severe in patients with darker skin types, but this is likely because of the delay in diagnosis.

The problem with overlooking nail psoriasis in patients of any skin color is the significant and independent adverse impact imposed by nail disease on quality of life, she added. She recounted the case of a 22-year-old Black patient whose nail psoriasis was overlooked even as she was being treated for her skin lesions.

“The diagnosis of nail psoriasis was missed for 3 years,” said Dr. Lipner, noting that the nail involvement was not trivial. “She had trouble doing her daily activities of life, but also, she was very embarrassed by her nails, not surprisingly.”

The problem of underrepresentation of Blacks in photos depicting nail diseases is not going unnoticed.

“Recently, there has been a concerted effort on the part of authors and editors to include more images of skin of color patients in published articles and textbooks,” said Jane S. Bellet, MD, professor of dermatology, Duke University, Durham, N.C.

An expert in nail disorders, particularly in children, Dr. Bellet said in an interview that this trend “must continue and increase in volume.” She said that the need for more images of nail disease in skin of color is not restricted to textbooks but includes “other learning materials, such as online atlases.”

Dr. Lipner and Dr. Bellet reported no potential conflicts of interest relative to this topic.

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.