Article

Key clinical point: Ultrasound assessment of entheses may help differentiate psoriatic arthritis (PsA) from fibromyalgia syndrome (FMS) as patients with PsA showed more frequent ultrasound changes both in gray scale (GS) and power Doppler (PD) mode than those with FMS.

Major finding: A higher proportion of patients with PsA vs. FMS was detected with ≥1 entheses in GS (P < .0001) and PD (P = .0033) mode, with GS and PD identifying changes in a higher proportion of PsA vs. FMS entheses (P < .0001 for both). Area under the curve values for GS and PD mode were 0.77 and 0.66, respectively, with 3.5 being the best cutoff GS score to discriminate PsA from FMS (sensitivity, 0.75; specificity, 0.63).

Study details: Findings are from a post hoc analysis of the cross‐sectional ULISSE study including 140 and 51 patients with PsA and FMS, respectively.

Disclosures: This study was funded by AbbVie Srl. Three authors declared being employees and shareholders of AbbVie, and some of the authors declared receiving consultancy fees and research support from several sources.

Source: Marchesoni A et al. J Clin Med. 2021;11(1):180 (Dec 29). Doi: 10.3390/jcm11010180.

Key clinical point: Ultrasound assessment of entheses may help differentiate psoriatic arthritis (PsA) from fibromyalgia syndrome (FMS) as patients with PsA showed more frequent ultrasound changes both in gray scale (GS) and power Doppler (PD) mode than those with FMS.

Major finding: A higher proportion of patients with PsA vs. FMS was detected with ≥1 entheses in GS (P < .0001) and PD (P = .0033) mode, with GS and PD identifying changes in a higher proportion of PsA vs. FMS entheses (P < .0001 for both). Area under the curve values for GS and PD mode were 0.77 and 0.66, respectively, with 3.5 being the best cutoff GS score to discriminate PsA from FMS (sensitivity, 0.75; specificity, 0.63).

Study details: Findings are from a post hoc analysis of the cross‐sectional ULISSE study including 140 and 51 patients with PsA and FMS, respectively.

Disclosures: This study was funded by AbbVie Srl. Three authors declared being employees and shareholders of AbbVie, and some of the authors declared receiving consultancy fees and research support from several sources.

Source: Marchesoni A et al. J Clin Med. 2021;11(1):180 (Dec 29). Doi: 10.3390/jcm11010180.

Key clinical point: Ultrasound assessment of entheses may help differentiate psoriatic arthritis (PsA) from fibromyalgia syndrome (FMS) as patients with PsA showed more frequent ultrasound changes both in gray scale (GS) and power Doppler (PD) mode than those with FMS.

Major finding: A higher proportion of patients with PsA vs. FMS was detected with ≥1 entheses in GS (P < .0001) and PD (P = .0033) mode, with GS and PD identifying changes in a higher proportion of PsA vs. FMS entheses (P < .0001 for both). Area under the curve values for GS and PD mode were 0.77 and 0.66, respectively, with 3.5 being the best cutoff GS score to discriminate PsA from FMS (sensitivity, 0.75; specificity, 0.63).

Study details: Findings are from a post hoc analysis of the cross‐sectional ULISSE study including 140 and 51 patients with PsA and FMS, respectively.

Disclosures: This study was funded by AbbVie Srl. Three authors declared being employees and shareholders of AbbVie, and some of the authors declared receiving consultancy fees and research support from several sources.

Source: Marchesoni A et al. J Clin Med. 2021;11(1):180 (Dec 29). Doi: 10.3390/jcm11010180.

Key clinical point: This real-world study confirms sustained improvements in signs and symptoms of psoriatic arthritis (PsA) with apremilast along with a tolerable safety profile.

Major finding: Overall, 43.5% of patients who received apremilast within 30 days of participating in the study and completed ≥150 days of treatment achieved PsA Response Criteria. In detail, 26.8% and 41.8% of patients with 68-tender joint count >0 and 66-swollen joint count >0 at baseline, respectively, achieved complete joint count resolution at month 6. No new adverse events were reported.

Study details: Findings are from the prospective, observational APOLO study including 107 patients with active PsA, of which 106 patients received ≥1 dose of apremilast.

Disclosures: This study was funded by Celgene. Some of the authors declared receiving research grants and consultancy and speaker fees from Celgene and other sources.

Source: Vlam KD et al. Adv Ther. 2022 (Jan 3). Doi: 10.1007/s12325-021-02016-x.

Key clinical point: This real-world study confirms sustained improvements in signs and symptoms of psoriatic arthritis (PsA) with apremilast along with a tolerable safety profile.

Major finding: Overall, 43.5% of patients who received apremilast within 30 days of participating in the study and completed ≥150 days of treatment achieved PsA Response Criteria. In detail, 26.8% and 41.8% of patients with 68-tender joint count >0 and 66-swollen joint count >0 at baseline, respectively, achieved complete joint count resolution at month 6. No new adverse events were reported.

Study details: Findings are from the prospective, observational APOLO study including 107 patients with active PsA, of which 106 patients received ≥1 dose of apremilast.

Disclosures: This study was funded by Celgene. Some of the authors declared receiving research grants and consultancy and speaker fees from Celgene and other sources.

Source: Vlam KD et al. Adv Ther. 2022 (Jan 3). Doi: 10.1007/s12325-021-02016-x.

Key clinical point: This real-world study confirms sustained improvements in signs and symptoms of psoriatic arthritis (PsA) with apremilast along with a tolerable safety profile.

Major finding: Overall, 43.5% of patients who received apremilast within 30 days of participating in the study and completed ≥150 days of treatment achieved PsA Response Criteria. In detail, 26.8% and 41.8% of patients with 68-tender joint count >0 and 66-swollen joint count >0 at baseline, respectively, achieved complete joint count resolution at month 6. No new adverse events were reported.

Study details: Findings are from the prospective, observational APOLO study including 107 patients with active PsA, of which 106 patients received ≥1 dose of apremilast.

Disclosures: This study was funded by Celgene. Some of the authors declared receiving research grants and consultancy and speaker fees from Celgene and other sources.

Source: Vlam KD et al. Adv Ther. 2022 (Jan 3). Doi: 10.1007/s12325-021-02016-x.

Key clinical point: Patients with psoriasis were more likely to have a delayed onset of psoriatic arthritis (PsA) if they were diagnosed with psoriasis at a younger age or suffered from severe psoriasis.

Major finding: The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA.

Study details: Findings are from a retrospective nested case-control study including 158 patients with incident PsA, of which 41% had concurrent psoriasis and 59% patients had onset of psoriasis before PsA.

Disclosures: This study was funded by the Rochester Epidemiology Project supported by National Institute on Aging, National Center for Advancing Translational Sciences, and others. The authors declared serving as consultants or receiving grants, consulting fees, honoraria, and research support from several sources.

Source: Karmacharya P et al. Semin Arthritis Rheum. 2021;151949 (Dec 31). Doi:  10.1016/j.semarthrit.2021.12.013.

Key clinical point: Patients with psoriasis were more likely to have a delayed onset of psoriatic arthritis (PsA) if they were diagnosed with psoriasis at a younger age or suffered from severe psoriasis.

Major finding: The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA.

Study details: Findings are from a retrospective nested case-control study including 158 patients with incident PsA, of which 41% had concurrent psoriasis and 59% patients had onset of psoriasis before PsA.

Disclosures: This study was funded by the Rochester Epidemiology Project supported by National Institute on Aging, National Center for Advancing Translational Sciences, and others. The authors declared serving as consultants or receiving grants, consulting fees, honoraria, and research support from several sources.

Source: Karmacharya P et al. Semin Arthritis Rheum. 2021;151949 (Dec 31). Doi:  10.1016/j.semarthrit.2021.12.013.

Key clinical point: Patients with psoriasis were more likely to have a delayed onset of psoriatic arthritis (PsA) if they were diagnosed with psoriasis at a younger age or suffered from severe psoriasis.

Major finding: The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA.

Study details: Findings are from a retrospective nested case-control study including 158 patients with incident PsA, of which 41% had concurrent psoriasis and 59% patients had onset of psoriasis before PsA.

Disclosures: This study was funded by the Rochester Epidemiology Project supported by National Institute on Aging, National Center for Advancing Translational Sciences, and others. The authors declared serving as consultants or receiving grants, consulting fees, honoraria, and research support from several sources.

Source: Karmacharya P et al. Semin Arthritis Rheum. 2021;151949 (Dec 31). Doi:  10.1016/j.semarthrit.2021.12.013.

Key clinical point: Presence of dactylitis independently confirmed more severe disease burden with higher swollen joint counts (SJC), C-reactive protein (CRP) levels, ultrasound-detected synovitis, and bone erosion in disease-modifying antirheumatic drug (DMARD)-naive patients with early psoriatic arthritis (PsA).

Major finding: Dactylitic vs. nondactylitic PsA was associated with a higher SJC (P < .001) and CRP level (P = .006) and a higher prevalence of ultrasound synovitis (P < .001) and bone erosions (P < .001). After excluding dactylitic digits, SJC was greater (P = .002) and ultrasound-detected synovitis (P < .001) and erosions (P = .008) were more prevalent in dactylitic vs. nondactylitic PsA.

Study details: This study included 177 DMARD-naive patients with early PsA who were stratified by the presence or absence of dactylitis at baseline.

Disclosures: This study was funded by the National Institute for Health Research Leeds Biomedical Research Centre. The authors declared no conflict of interests.

Source: Dubash S et al. Ann Rheum Dis. 2021 (Dec 10). Doi: 10.1136/annrheumdis-2021-220964.

Key clinical point: Presence of dactylitis independently confirmed more severe disease burden with higher swollen joint counts (SJC), C-reactive protein (CRP) levels, ultrasound-detected synovitis, and bone erosion in disease-modifying antirheumatic drug (DMARD)-naive patients with early psoriatic arthritis (PsA).

Major finding: Dactylitic vs. nondactylitic PsA was associated with a higher SJC (P < .001) and CRP level (P = .006) and a higher prevalence of ultrasound synovitis (P < .001) and bone erosions (P < .001). After excluding dactylitic digits, SJC was greater (P = .002) and ultrasound-detected synovitis (P < .001) and erosions (P = .008) were more prevalent in dactylitic vs. nondactylitic PsA.

Study details: This study included 177 DMARD-naive patients with early PsA who were stratified by the presence or absence of dactylitis at baseline.

Disclosures: This study was funded by the National Institute for Health Research Leeds Biomedical Research Centre. The authors declared no conflict of interests.

Source: Dubash S et al. Ann Rheum Dis. 2021 (Dec 10). Doi: 10.1136/annrheumdis-2021-220964.

Key clinical point: Presence of dactylitis independently confirmed more severe disease burden with higher swollen joint counts (SJC), C-reactive protein (CRP) levels, ultrasound-detected synovitis, and bone erosion in disease-modifying antirheumatic drug (DMARD)-naive patients with early psoriatic arthritis (PsA).

Major finding: Dactylitic vs. nondactylitic PsA was associated with a higher SJC (P < .001) and CRP level (P = .006) and a higher prevalence of ultrasound synovitis (P < .001) and bone erosions (P < .001). After excluding dactylitic digits, SJC was greater (P = .002) and ultrasound-detected synovitis (P < .001) and erosions (P = .008) were more prevalent in dactylitic vs. nondactylitic PsA.

Study details: This study included 177 DMARD-naive patients with early PsA who were stratified by the presence or absence of dactylitis at baseline.

Disclosures: This study was funded by the National Institute for Health Research Leeds Biomedical Research Centre. The authors declared no conflict of interests.

Source: Dubash S et al. Ann Rheum Dis. 2021 (Dec 10). Doi: 10.1136/annrheumdis-2021-220964.

Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: Risankizumab effectively reduced clinical manifestations of psoriatic arthritis (PsA) in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with no new adverse events (AE).

Major finding: At week 24, at least a 20% improvement in the American College of Rheumatology score was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent AEs were mild/moderate and reported at similar frequencies in risankizumab (40.4%) and placebo (38.7%) groups.

Study details: Findings are from a double-blind, phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to ≥1 csDMARDs who were randomly assigned to receive 150 mg risankizumab or placebo at weeks 0, 4, and 16.

Disclosures: This study did not report any source of funding. The authors declared serving as speaker, consultant, investigator, or receiving honoraria, fees, and grants from several sources. Five authors declared being employees or shareholders of AbbVie.

Source: Kristensen LE et al. Ann Rheum Dis. 2021;81:225-231 (Dec 15). Doi: 10.1136/annrheumdis-2021-221019.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: In patients with psoriatic arthritis (PsA), clinical inflammation monitored by swollen joint counts (SJC) and biochemical inflammation monitored by C-reactive protein (CRP) level, have a direct effect on structural progression.

Major finding: Progression was significantly higher in patients with active vs. inactive time-averaged SJC (odds ratio [OR] 1.24; P = .016) and time-averaged CRP (OR 6.08; P = .036). Progression was greatest in presence of both clinical and biochemical inflammation and lowest in absence of both (P = .05).

Study details: Findings are secondary analysis of patient data from the IMPACT 2 trial, including 145 patients with PsA.

Disclosures: The study did not report any source of funding. The authors declared serving as associate editor or receiving grants and honoraria from several sources.

Source: Borst C et al. RMD Open. 2021;7:e002038 (Dec 8). Doi: 10.1136/rmdopen-2021-002038.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Upadacitinib showed similar efficacy and a consistent safety profile as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs) in patients with psoriatic arthritis (PsA).

Major finding: At week 12, ≥20% improvement in the American College of Rheumatology score was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI, 24.4%-43.1%; 30 mg: 45.7%; 95% CI, 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI, 27.9%-40.1%; 30 mg: 39.6%; 95% CI, 33.7%-45.5%). Adverse events were generally similar with monotherapy and combination therapy.

Study details: This is a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2, including 1,916 patients with active PsA with an inadequate response to ≥1 nbDMARD/bDMARD who were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks.

Disclosures: This work was supported by AbbVie. Six authors reported being employees and stockholders of AbbVie. The other authors reported ties with several sources including AbbVie.

Source: Nash P et al. Rheumatology (Oxford). 2021;keab905 (Dec 3). Doi:  10.1093/rheumatology/keab905.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

Key clinical point: Continuation of tumor necrosis factor (TNF) inhibitor therapy throughout the vaccination period was safe and did not hamper the immune response elicited by BNT162b2 (BioNTech-Pfizer) mRNA SARS-CoV-2 vaccine in patients with psoriatic arthritis (PsA).

Major finding: There was no change in Clinical Disease Activity Index in patients with PsA before and after vaccination (P = .92). After 2 doses of BNT162b2 mRNA SARS-CoV-2 vaccine, all patients with PsA showed a positive immune response with mean anti-SARS-CoV-2 antibody level not significantly different from matched controls (P = .08).

Study details: Findings are from a prospective study including 40 patients with PsA on TNF inhibitor therapy matched with 40 healthy controls; both groups received 2 shots of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Disclosures: The study did not report any source of funding. The authors declared no conflict of interests.

Source: Venerito V et al. RMD Open. 2022;8:e001847 (Jan 5). Doi: 10.1136/ rmdopen-2021-001847.

THE COMPARISON

A Pink, elevated, granulomatous, indurated plaques on the face, including the nasal alae, of a 52-year-old woman with a darker skin tone.

B Orange and pink, elevated, granulomatous, indurated plaques on the face of a 55-year-old woman with a lighter skin tone.

Sarcoidosis is a granulomatous disease that may affect the skin in addition to multiple body organ systems, including the lungs. Bilateral hilar adenopathy on a chest radiograph is the most common finding. Sarcoidosis also has a variety of cutaneous manifestations. Early diagnosis is vital, as patients with sarcoidosis and pulmonary fibrosis have a shortened life span compared to the overall population.¹ With a growing skin of color population, it is important to recognize sarcoidosis as soon as possible.²

Epidemiology

People of African descent have the highest sarcoidosis prevalence in the United States.³ In the United States, the incidence of sarcoidosis in Black individuals peaks in the fourth decade of life. A 5-year study in a US health maintenance organization found that the age-adjusted annual incidence was 10.9 per 100,000 cases among Whites and 35.5 per 100,000 cases among Blacks.⁴

Key clinical features in people with darker skin tones:

• Papules are seen in sarcoidosis, primarily on the face, and may start as orange hued or yellow-brown and then become brown-red or pink to violaceous before involuting into faint macules.^5-7

• When round or oval sarcoid plaques appear, they often are more erythematous.

• In skin of color, plaques may become hypopigmented.⁸

• Erythema nodosum, the most common nonspecific cutaneous lesion seen in sarcoidosis, is less commonly seen in those of African and Asian descent.^9-11 This is in contrast to distinctive forms of specific sarcoid skin lesions such as lupus pernio and scar sarcoidosis, as well as papules and plaques and minor forms of specific sarcoid skin lesions including subcutaneous nodules; hypopigmented macules; psoriasiform lesions; and ulcerative, localized erythrodermic, ichthyosiform, scalp, and nail lesions.

• Lupus pernio is a cutaneous manifestation of sarcoidosis that appears on the face. It looks similar to lupus erythematosus and occurs most commonly in women of African descent.^8,12

• Hypopigmented lesions are more common in those with darker skin tones.⁹

• Ulcerative lesions are more common in those of African descent and women.¹³

• Scalp sarcoidosis is more common in patients of African descent.¹⁴

• Sarcoidosis may develop at sites of trauma, such as scars and tattoos.^15-17

Worth noting

The cutaneous lesions seen in sarcoidosis may be emotionally devastating and disfiguring. Due to the variety of clinical manifestations, sarcoidosis may be misdiagnosed, leading to delays in treatment.¹⁸

Health disparity highlight

Patients older than 40 years presenting with sarcoidosis and those of African descent have a worse prognosis.19 Despite adjustment for race, ethnic group, age, and sex, patients with low income and financial barriers present with more severe sarcoidosis.²⁰

THE COMPARISON

A Pink, elevated, granulomatous, indurated plaques on the face, including the nasal alae, of a 52-year-old woman with a darker skin tone.

B Orange and pink, elevated, granulomatous, indurated plaques on the face of a 55-year-old woman with a lighter skin tone.

Sarcoidosis is a granulomatous disease that may affect the skin in addition to multiple body organ systems, including the lungs. Bilateral hilar adenopathy on a chest radiograph is the most common finding. Sarcoidosis also has a variety of cutaneous manifestations. Early diagnosis is vital, as patients with sarcoidosis and pulmonary fibrosis have a shortened life span compared to the overall population.¹ With a growing skin of color population, it is important to recognize sarcoidosis as soon as possible.²

Epidemiology

People of African descent have the highest sarcoidosis prevalence in the United States.³ In the United States, the incidence of sarcoidosis in Black individuals peaks in the fourth decade of life. A 5-year study in a US health maintenance organization found that the age-adjusted annual incidence was 10.9 per 100,000 cases among Whites and 35.5 per 100,000 cases among Blacks.⁴

Key clinical features in people with darker skin tones:

• Papules are seen in sarcoidosis, primarily on the face, and may start as orange hued or yellow-brown and then become brown-red or pink to violaceous before involuting into faint macules.^5-7

• When round or oval sarcoid plaques appear, they often are more erythematous.

• In skin of color, plaques may become hypopigmented.⁸

• Erythema nodosum, the most common nonspecific cutaneous lesion seen in sarcoidosis, is less commonly seen in those of African and Asian descent.^9-11 This is in contrast to distinctive forms of specific sarcoid skin lesions such as lupus pernio and scar sarcoidosis, as well as papules and plaques and minor forms of specific sarcoid skin lesions including subcutaneous nodules; hypopigmented macules; psoriasiform lesions; and ulcerative, localized erythrodermic, ichthyosiform, scalp, and nail lesions.

• Lupus pernio is a cutaneous manifestation of sarcoidosis that appears on the face. It looks similar to lupus erythematosus and occurs most commonly in women of African descent.^8,12

• Hypopigmented lesions are more common in those with darker skin tones.⁹

• Ulcerative lesions are more common in those of African descent and women.¹³

• Scalp sarcoidosis is more common in patients of African descent.¹⁴

• Sarcoidosis may develop at sites of trauma, such as scars and tattoos.^15-17

Worth noting

The cutaneous lesions seen in sarcoidosis may be emotionally devastating and disfiguring. Due to the variety of clinical manifestations, sarcoidosis may be misdiagnosed, leading to delays in treatment.¹⁸

Health disparity highlight

Patients older than 40 years presenting with sarcoidosis and those of African descent have a worse prognosis.19 Despite adjustment for race, ethnic group, age, and sex, patients with low income and financial barriers present with more severe sarcoidosis.²⁰

THE COMPARISON

A Pink, elevated, granulomatous, indurated plaques on the face, including the nasal alae, of a 52-year-old woman with a darker skin tone.

B Orange and pink, elevated, granulomatous, indurated plaques on the face of a 55-year-old woman with a lighter skin tone.

Sarcoidosis is a granulomatous disease that may affect the skin in addition to multiple body organ systems, including the lungs. Bilateral hilar adenopathy on a chest radiograph is the most common finding. Sarcoidosis also has a variety of cutaneous manifestations. Early diagnosis is vital, as patients with sarcoidosis and pulmonary fibrosis have a shortened life span compared to the overall population.¹ With a growing skin of color population, it is important to recognize sarcoidosis as soon as possible.²

Epidemiology

People of African descent have the highest sarcoidosis prevalence in the United States.³ In the United States, the incidence of sarcoidosis in Black individuals peaks in the fourth decade of life. A 5-year study in a US health maintenance organization found that the age-adjusted annual incidence was 10.9 per 100,000 cases among Whites and 35.5 per 100,000 cases among Blacks.⁴

Key clinical features in people with darker skin tones:

• Papules are seen in sarcoidosis, primarily on the face, and may start as orange hued or yellow-brown and then become brown-red or pink to violaceous before involuting into faint macules.^5-7

• When round or oval sarcoid plaques appear, they often are more erythematous.

• In skin of color, plaques may become hypopigmented.⁸

• Erythema nodosum, the most common nonspecific cutaneous lesion seen in sarcoidosis, is less commonly seen in those of African and Asian descent.^9-11 This is in contrast to distinctive forms of specific sarcoid skin lesions such as lupus pernio and scar sarcoidosis, as well as papules and plaques and minor forms of specific sarcoid skin lesions including subcutaneous nodules; hypopigmented macules; psoriasiform lesions; and ulcerative, localized erythrodermic, ichthyosiform, scalp, and nail lesions.

• Lupus pernio is a cutaneous manifestation of sarcoidosis that appears on the face. It looks similar to lupus erythematosus and occurs most commonly in women of African descent.^8,12

• Hypopigmented lesions are more common in those with darker skin tones.⁹

• Ulcerative lesions are more common in those of African descent and women.¹³

• Scalp sarcoidosis is more common in patients of African descent.¹⁴

• Sarcoidosis may develop at sites of trauma, such as scars and tattoos.^15-17

Worth noting

The cutaneous lesions seen in sarcoidosis may be emotionally devastating and disfiguring. Due to the variety of clinical manifestations, sarcoidosis may be misdiagnosed, leading to delays in treatment.¹⁸

Health disparity highlight

Patients older than 40 years presenting with sarcoidosis and those of African descent have a worse prognosis.19 Despite adjustment for race, ethnic group, age, and sex, patients with low income and financial barriers present with more severe sarcoidosis.²⁰

ILLUSTRATIVE CASE

A 26-year-old man presents to the emergency department complaining of sudden-onset left-side chest pain and mild dyspnea that started while he was playing basketball. He denies any medical problems and takes no medications. He is able to speak in complete sentences as he answers your questions. His O₂ saturation is 95% and a chest x-ray reveals a left-side, moderate-to-large pneumothorax.

A primary spontaneous pneumothorax is one that occurs in the absence of underlying clinical lung disease and is not associated with an inciting cause, such as a rib fracture.² In the United States, the estimated incidence of primary spontaneous pneumothorax is 7.4 cases per 100,000 men and 1.2 cases per 100,000 women.³ The etiology is often unknown, but it is associated with several risk factors, including male sex, smoking, and a tall, thin body habitus.²

The management strategy for stable patients with a primary spontaneous pneumothorax largely depends on pneumothorax size and institutional practice. Multiple methods define pneumothorax size; the US standard cutoff for a small or large pneumothorax is 3 cm, between the pleural line and chest wall at the level of the apex,⁴ compared with 2 cm in Europe, when evaluating the distance at the hilum in an upright chest radiograph.⁵ The Collins method uses a formula to calculate the percentage of lung area affected based on 3 distinct measurements on a posterior/anterior upright chest radiograph.⁶

Management options include observation, supplemental oxygen, simple aspiration, and thoracostomy or chest tube placement. British Thoracic Society guidelines published in 2010 state that only a small pneumothorax can be managed conservatively with observation alone; for a large pneumothorax, the guidelines recommend needle aspiration to achieve lung reinflation, followed by chest tube placement if unsuccessful.⁵

In practice, management of a large primary spontaneous pneumothorax varies, but the most common treatment is chest tube placement.⁷ This procedure can be painful and may result in complications such as bleeding, infection, injury to internal structures, or the need for surgical intervention.⁷ In addition, once a chest tube is placed, hospital admission ensues, lasting an average of 4 days.⁸ Given these consequences, there is a need for safe and feasible treatment options for a large primary spontaneous pneumothorax.

STUDY SUMMARY

Observational management judged noninferior, with multiple advantages

The Primary Spontaneous Pneumothorax (PSP) trial was a prospective noninferiority trial conducted at 39 hospitals in Australia and New Zealand. This randomized controlled trial compared observational (“watch and wait”) vs interventional (chest tube placement) management of uncomplicated, unilateral, primary spontaneous pneumothorax. Patients ages 14 to 50 years with a moderate-to-large pneumothorax—32% or greater, as defined by the Collins method⁴—were randomly assigned to a study group to examine the primary outcome of lung reexpansion at 8 weeks.

“Watch-and-wait” management spared 85% of the patients from invasive intervention.

The intervention included chest tube insertion attached to an underwater seal without suction for 1 hour, followed by an x-ray and clamping for 4 hours if there was no air leak, followed by a repeat chest x-ray. If there was no evidence of radiographic resolution, or if during observation the pneumothorax recurred, the underwater seal was recommenced and the patient was admitted to the hospital, with further intervention at the discretion of the inpatient clinicians. If radiographic improvement was seen, the tube was removed and the patient discharged.

Continue to: In contrast...

In contrast, conservative management entailed patient observation for at least 4 hours followed by a repeat chest x-ray. If after the observation period, patients were walking comfortably and without supplemental oxygen, they were discharged. Patients in the observation group underwent an intervention if they met a variety of criteria, including unstable vitals or an enlarging pneumothorax. All patients received standard care with analgesia and supplemental oxygen as needed.

A total of 316 patients were randomized, with 154 assigned to the intervention group and 162 to the observation group. The mean age for all participants was 26. Most patients were male (84.4% in the intervention group and 87.7% in the observation group) and almost half were current smokers (49.3% in the intervention and 42.5% in the observation group). The mean body mass index of participants was 21.4 in the intervention and 21.3 in the observation group. Twenty-five patients (15%) in the observation group underwent interventions for reasons specified in the research protocol (eg, “significant symptoms” such as abnormal physiologic observations and intolerable symptoms, or patient unwillingness to continue in the assigned group), and 10 patients assigned to the intervention group declined treatment.

Using a complete-case analysis, 129 of 131 patients (98.5%) in the intervention group and 118 of 125 patients (94.4%) in the observation group met the primary outcome of radiographic resolution within 8 weeks (risk difference [RD] = –4.1%; 95% CI, –8.6 to 0.5), thereby falling within the prespecified margin for noninferiority of less than 9%.

This study opens the possibility of managing selected patients with spontaneous pneumothorax in an outpatient setting.

Per-protocol analysis at 8 weeks also proved observational management noninferior, with 124 of 126 patients (98.4%) in the intervention group and 123 of 130 patients (94.6%) in the observation group achieving lung reexpansion within 8 weeks (RD = –3.8%; 95% CI, –8.3 to 0.7). The time to symptom resolution was similar between groups, with a median time of 15.5 days in the intervention group compared with 14 days in the observation group (hazard ratio = 1.11; 95% CI, 0.88-1.4). A lower risk of serious adverse events (relative risk [RR] = 3.3; 95% CI, 1.37-8.1) and pneumothorax recurrence (absolute RD = 8%; 95% CI, 0.5-15.4) occurred in the observation group vs the intervention group. The average length of hospital stay for patients in the intervention group was 6.1 days, vs 1.6 days in the observation group (RR = 2.8; 95% CI, 1.8-3.6).

Two additional sensitivity analyses were performed because multiple study participants were lost to follow-up or had data collected after 8 weeks. Noninferiority was maintained when data collected after the 8-week visit were included and extended to 63 days (RD = –3.7%: 95% CI, –7.9 to 0.6). However, noninferiority was lost when missing data after 8 weeks were deemed “treatment failure” (RD = –11%; 95% CI, –18.4 to –3.5).

Continue to: WHAT'S NEW

WHAT’S NEW

Conservative management enabled most patients to avoid invasive Tx risks

In this specific patient population, conservative management of primary spontaneous pneumothorax was noninferior to interventional management and had a lower risk of serious adverse events. This management practice spared 85% of the patients from invasive intervention. As a result, they experienced a shortened hospital stay, fewer days missed from school or work, less exposure to radiation from repeat chest x-rays, and a lower rate of adverse events. Additionally, fewer of these patients had early pneumothorax recurrence.

CAVEATS

There were limitations in the trial’s original statistical design

This study had a specific follow-up timetable, and some of the participants were not examined until after the 8-week checkpoint or were lost to follow-up entirely. The authors attempted to address these limitations (and show transparency) by providing additional sensitivity analyses as well as providing the intention-to-treat and per-protocol analyses for the primary outcome at 8 weeks. Noninferiority was maintained in all analyses except for the sensitivity analysis that treated missing data as treatment failure. Therefore, the authors note these approaches result in “statistical fragility” and are exploratory.

CHALLENGES TO IMPLEMENTATION

Pneumothorax is not commonly seen in outpatient settings

Family physicians working in outpatient settings generally do not encounter pneumothorax and, using current guidelines, would refer for emergency or inpatient care. This study opens the possibility of managing selected patients in an outpatient setting; however, this would require at least a 4-hour period of observation, which may be impractical for many outpatient-based physicians. Additionally, the study uses the Collins method to define moderate-to-large pneumothorax, which is likely an uncommon practice and thus not applicable in most primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 26-year-old man presents to the emergency department complaining of sudden-onset left-side chest pain and mild dyspnea that started while he was playing basketball. He denies any medical problems and takes no medications. He is able to speak in complete sentences as he answers your questions. His O₂ saturation is 95% and a chest x-ray reveals a left-side, moderate-to-large pneumothorax.

A primary spontaneous pneumothorax is one that occurs in the absence of underlying clinical lung disease and is not associated with an inciting cause, such as a rib fracture.² In the United States, the estimated incidence of primary spontaneous pneumothorax is 7.4 cases per 100,000 men and 1.2 cases per 100,000 women.³ The etiology is often unknown, but it is associated with several risk factors, including male sex, smoking, and a tall, thin body habitus.²

The management strategy for stable patients with a primary spontaneous pneumothorax largely depends on pneumothorax size and institutional practice. Multiple methods define pneumothorax size; the US standard cutoff for a small or large pneumothorax is 3 cm, between the pleural line and chest wall at the level of the apex,⁴ compared with 2 cm in Europe, when evaluating the distance at the hilum in an upright chest radiograph.⁵ The Collins method uses a formula to calculate the percentage of lung area affected based on 3 distinct measurements on a posterior/anterior upright chest radiograph.⁶

Management options include observation, supplemental oxygen, simple aspiration, and thoracostomy or chest tube placement. British Thoracic Society guidelines published in 2010 state that only a small pneumothorax can be managed conservatively with observation alone; for a large pneumothorax, the guidelines recommend needle aspiration to achieve lung reinflation, followed by chest tube placement if unsuccessful.⁵

In practice, management of a large primary spontaneous pneumothorax varies, but the most common treatment is chest tube placement.⁷ This procedure can be painful and may result in complications such as bleeding, infection, injury to internal structures, or the need for surgical intervention.⁷ In addition, once a chest tube is placed, hospital admission ensues, lasting an average of 4 days.⁸ Given these consequences, there is a need for safe and feasible treatment options for a large primary spontaneous pneumothorax.

STUDY SUMMARY

Observational management judged noninferior, with multiple advantages

The Primary Spontaneous Pneumothorax (PSP) trial was a prospective noninferiority trial conducted at 39 hospitals in Australia and New Zealand. This randomized controlled trial compared observational (“watch and wait”) vs interventional (chest tube placement) management of uncomplicated, unilateral, primary spontaneous pneumothorax. Patients ages 14 to 50 years with a moderate-to-large pneumothorax—32% or greater, as defined by the Collins method⁴—were randomly assigned to a study group to examine the primary outcome of lung reexpansion at 8 weeks.

“Watch-and-wait” management spared 85% of the patients from invasive intervention.

The intervention included chest tube insertion attached to an underwater seal without suction for 1 hour, followed by an x-ray and clamping for 4 hours if there was no air leak, followed by a repeat chest x-ray. If there was no evidence of radiographic resolution, or if during observation the pneumothorax recurred, the underwater seal was recommenced and the patient was admitted to the hospital, with further intervention at the discretion of the inpatient clinicians. If radiographic improvement was seen, the tube was removed and the patient discharged.

Continue to: In contrast...

In contrast, conservative management entailed patient observation for at least 4 hours followed by a repeat chest x-ray. If after the observation period, patients were walking comfortably and without supplemental oxygen, they were discharged. Patients in the observation group underwent an intervention if they met a variety of criteria, including unstable vitals or an enlarging pneumothorax. All patients received standard care with analgesia and supplemental oxygen as needed.

A total of 316 patients were randomized, with 154 assigned to the intervention group and 162 to the observation group. The mean age for all participants was 26. Most patients were male (84.4% in the intervention group and 87.7% in the observation group) and almost half were current smokers (49.3% in the intervention and 42.5% in the observation group). The mean body mass index of participants was 21.4 in the intervention and 21.3 in the observation group. Twenty-five patients (15%) in the observation group underwent interventions for reasons specified in the research protocol (eg, “significant symptoms” such as abnormal physiologic observations and intolerable symptoms, or patient unwillingness to continue in the assigned group), and 10 patients assigned to the intervention group declined treatment.

Using a complete-case analysis, 129 of 131 patients (98.5%) in the intervention group and 118 of 125 patients (94.4%) in the observation group met the primary outcome of radiographic resolution within 8 weeks (risk difference [RD] = –4.1%; 95% CI, –8.6 to 0.5), thereby falling within the prespecified margin for noninferiority of less than 9%.

This study opens the possibility of managing selected patients with spontaneous pneumothorax in an outpatient setting.

Per-protocol analysis at 8 weeks also proved observational management noninferior, with 124 of 126 patients (98.4%) in the intervention group and 123 of 130 patients (94.6%) in the observation group achieving lung reexpansion within 8 weeks (RD = –3.8%; 95% CI, –8.3 to 0.7). The time to symptom resolution was similar between groups, with a median time of 15.5 days in the intervention group compared with 14 days in the observation group (hazard ratio = 1.11; 95% CI, 0.88-1.4). A lower risk of serious adverse events (relative risk [RR] = 3.3; 95% CI, 1.37-8.1) and pneumothorax recurrence (absolute RD = 8%; 95% CI, 0.5-15.4) occurred in the observation group vs the intervention group. The average length of hospital stay for patients in the intervention group was 6.1 days, vs 1.6 days in the observation group (RR = 2.8; 95% CI, 1.8-3.6).

Two additional sensitivity analyses were performed because multiple study participants were lost to follow-up or had data collected after 8 weeks. Noninferiority was maintained when data collected after the 8-week visit were included and extended to 63 days (RD = –3.7%: 95% CI, –7.9 to 0.6). However, noninferiority was lost when missing data after 8 weeks were deemed “treatment failure” (RD = –11%; 95% CI, –18.4 to –3.5).

Continue to: WHAT'S NEW

WHAT’S NEW

Conservative management enabled most patients to avoid invasive Tx risks

In this specific patient population, conservative management of primary spontaneous pneumothorax was noninferior to interventional management and had a lower risk of serious adverse events. This management practice spared 85% of the patients from invasive intervention. As a result, they experienced a shortened hospital stay, fewer days missed from school or work, less exposure to radiation from repeat chest x-rays, and a lower rate of adverse events. Additionally, fewer of these patients had early pneumothorax recurrence.

CAVEATS

There were limitations in the trial’s original statistical design

This study had a specific follow-up timetable, and some of the participants were not examined until after the 8-week checkpoint or were lost to follow-up entirely. The authors attempted to address these limitations (and show transparency) by providing additional sensitivity analyses as well as providing the intention-to-treat and per-protocol analyses for the primary outcome at 8 weeks. Noninferiority was maintained in all analyses except for the sensitivity analysis that treated missing data as treatment failure. Therefore, the authors note these approaches result in “statistical fragility” and are exploratory.

CHALLENGES TO IMPLEMENTATION

Pneumothorax is not commonly seen in outpatient settings

Family physicians working in outpatient settings generally do not encounter pneumothorax and, using current guidelines, would refer for emergency or inpatient care. This study opens the possibility of managing selected patients in an outpatient setting; however, this would require at least a 4-hour period of observation, which may be impractical for many outpatient-based physicians. Additionally, the study uses the Collins method to define moderate-to-large pneumothorax, which is likely an uncommon practice and thus not applicable in most primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 26-year-old man presents to the emergency department complaining of sudden-onset left-side chest pain and mild dyspnea that started while he was playing basketball. He denies any medical problems and takes no medications. He is able to speak in complete sentences as he answers your questions. His O₂ saturation is 95% and a chest x-ray reveals a left-side, moderate-to-large pneumothorax.

A primary spontaneous pneumothorax is one that occurs in the absence of underlying clinical lung disease and is not associated with an inciting cause, such as a rib fracture.² In the United States, the estimated incidence of primary spontaneous pneumothorax is 7.4 cases per 100,000 men and 1.2 cases per 100,000 women.³ The etiology is often unknown, but it is associated with several risk factors, including male sex, smoking, and a tall, thin body habitus.²

The management strategy for stable patients with a primary spontaneous pneumothorax largely depends on pneumothorax size and institutional practice. Multiple methods define pneumothorax size; the US standard cutoff for a small or large pneumothorax is 3 cm, between the pleural line and chest wall at the level of the apex,⁴ compared with 2 cm in Europe, when evaluating the distance at the hilum in an upright chest radiograph.⁵ The Collins method uses a formula to calculate the percentage of lung area affected based on 3 distinct measurements on a posterior/anterior upright chest radiograph.⁶

Management options include observation, supplemental oxygen, simple aspiration, and thoracostomy or chest tube placement. British Thoracic Society guidelines published in 2010 state that only a small pneumothorax can be managed conservatively with observation alone; for a large pneumothorax, the guidelines recommend needle aspiration to achieve lung reinflation, followed by chest tube placement if unsuccessful.⁵

In practice, management of a large primary spontaneous pneumothorax varies, but the most common treatment is chest tube placement.⁷ This procedure can be painful and may result in complications such as bleeding, infection, injury to internal structures, or the need for surgical intervention.⁷ In addition, once a chest tube is placed, hospital admission ensues, lasting an average of 4 days.⁸ Given these consequences, there is a need for safe and feasible treatment options for a large primary spontaneous pneumothorax.

STUDY SUMMARY

Observational management judged noninferior, with multiple advantages

The Primary Spontaneous Pneumothorax (PSP) trial was a prospective noninferiority trial conducted at 39 hospitals in Australia and New Zealand. This randomized controlled trial compared observational (“watch and wait”) vs interventional (chest tube placement) management of uncomplicated, unilateral, primary spontaneous pneumothorax. Patients ages 14 to 50 years with a moderate-to-large pneumothorax—32% or greater, as defined by the Collins method⁴—were randomly assigned to a study group to examine the primary outcome of lung reexpansion at 8 weeks.

“Watch-and-wait” management spared 85% of the patients from invasive intervention.

The intervention included chest tube insertion attached to an underwater seal without suction for 1 hour, followed by an x-ray and clamping for 4 hours if there was no air leak, followed by a repeat chest x-ray. If there was no evidence of radiographic resolution, or if during observation the pneumothorax recurred, the underwater seal was recommenced and the patient was admitted to the hospital, with further intervention at the discretion of the inpatient clinicians. If radiographic improvement was seen, the tube was removed and the patient discharged.

Continue to: In contrast...

In contrast, conservative management entailed patient observation for at least 4 hours followed by a repeat chest x-ray. If after the observation period, patients were walking comfortably and without supplemental oxygen, they were discharged. Patients in the observation group underwent an intervention if they met a variety of criteria, including unstable vitals or an enlarging pneumothorax. All patients received standard care with analgesia and supplemental oxygen as needed.

A total of 316 patients were randomized, with 154 assigned to the intervention group and 162 to the observation group. The mean age for all participants was 26. Most patients were male (84.4% in the intervention group and 87.7% in the observation group) and almost half were current smokers (49.3% in the intervention and 42.5% in the observation group). The mean body mass index of participants was 21.4 in the intervention and 21.3 in the observation group. Twenty-five patients (15%) in the observation group underwent interventions for reasons specified in the research protocol (eg, “significant symptoms” such as abnormal physiologic observations and intolerable symptoms, or patient unwillingness to continue in the assigned group), and 10 patients assigned to the intervention group declined treatment.

Using a complete-case analysis, 129 of 131 patients (98.5%) in the intervention group and 118 of 125 patients (94.4%) in the observation group met the primary outcome of radiographic resolution within 8 weeks (risk difference [RD] = –4.1%; 95% CI, –8.6 to 0.5), thereby falling within the prespecified margin for noninferiority of less than 9%.

This study opens the possibility of managing selected patients with spontaneous pneumothorax in an outpatient setting.

Per-protocol analysis at 8 weeks also proved observational management noninferior, with 124 of 126 patients (98.4%) in the intervention group and 123 of 130 patients (94.6%) in the observation group achieving lung reexpansion within 8 weeks (RD = –3.8%; 95% CI, –8.3 to 0.7). The time to symptom resolution was similar between groups, with a median time of 15.5 days in the intervention group compared with 14 days in the observation group (hazard ratio = 1.11; 95% CI, 0.88-1.4). A lower risk of serious adverse events (relative risk [RR] = 3.3; 95% CI, 1.37-8.1) and pneumothorax recurrence (absolute RD = 8%; 95% CI, 0.5-15.4) occurred in the observation group vs the intervention group. The average length of hospital stay for patients in the intervention group was 6.1 days, vs 1.6 days in the observation group (RR = 2.8; 95% CI, 1.8-3.6).

Two additional sensitivity analyses were performed because multiple study participants were lost to follow-up or had data collected after 8 weeks. Noninferiority was maintained when data collected after the 8-week visit were included and extended to 63 days (RD = –3.7%: 95% CI, –7.9 to 0.6). However, noninferiority was lost when missing data after 8 weeks were deemed “treatment failure” (RD = –11%; 95% CI, –18.4 to –3.5).

Continue to: WHAT'S NEW

WHAT’S NEW

Conservative management enabled most patients to avoid invasive Tx risks

In this specific patient population, conservative management of primary spontaneous pneumothorax was noninferior to interventional management and had a lower risk of serious adverse events. This management practice spared 85% of the patients from invasive intervention. As a result, they experienced a shortened hospital stay, fewer days missed from school or work, less exposure to radiation from repeat chest x-rays, and a lower rate of adverse events. Additionally, fewer of these patients had early pneumothorax recurrence.

CAVEATS

There were limitations in the trial’s original statistical design

This study had a specific follow-up timetable, and some of the participants were not examined until after the 8-week checkpoint or were lost to follow-up entirely. The authors attempted to address these limitations (and show transparency) by providing additional sensitivity analyses as well as providing the intention-to-treat and per-protocol analyses for the primary outcome at 8 weeks. Noninferiority was maintained in all analyses except for the sensitivity analysis that treated missing data as treatment failure. Therefore, the authors note these approaches result in “statistical fragility” and are exploratory.

CHALLENGES TO IMPLEMENTATION

Pneumothorax is not commonly seen in outpatient settings

Family physicians working in outpatient settings generally do not encounter pneumothorax and, using current guidelines, would refer for emergency or inpatient care. This study opens the possibility of managing selected patients in an outpatient setting; however, this would require at least a 4-hour period of observation, which may be impractical for many outpatient-based physicians. Additionally, the study uses the Collins method to define moderate-to-large pneumothorax, which is likely an uncommon practice and thus not applicable in most primary care settings.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.