About

Peter A. Merkel, M.D., M.P.H., is a Professor of Medicine specializing in Rheumatology at the University of Pennsylvania's Perelman School of Medicine. He serves as the Chief of the Division of Rheumatology at the Hospital of the University of Pennsylvania. His educational background includes a B.A. from Wesleyan University, an M.D. from Yale University School of Medicine, and an M.P.H. from Harvard School of Public Health. His professional focus encompasses the study and treatment of vasculitis and other autoimmune rheumatic diseases, with a significant emphasis on clinical research and patient care. Dr. Merkel has contributed to numerous research publications in the field of vasculitis and autoimmune diseases, advancing understanding of disease mechanisms and therapeutic approaches.

Research topics

• Medicine
• Internal medicine
• Pathology
• Immunology
• Intensive care medicine
• Biology
• Surgery
• Gastroenterology

Selected publications

• Patients’ perspectives of eosinophilic granulomatosis with polyangiitis within the context of a clinical trial

  EULAR Rheumatology Open · 2025-10-01

  articleOpen access1st authorCorresponding

  Eosinophilic granulomatosis with polyangiitis (EGPA) is a complex, multisystem form of vasculitis. MANDARA (NCT04157348) was a phase 3 clinical trial comparing the efficacy and safety of benralizumab versus mepolizumab, in addition to standard of care, for relapsing/refractory EGPA. This qualitative interview substudy explored study participants’ experiences with EGPA and their participation in the trial. Thirty-eight patients from 5 countries participating in MANDARA opted into a longitudinal qualitative substudy, which comprised two 60-minute, semistructured, one-to-one telephone interviews conducted by trained interviewers between December 2019 and June 2023. Topics discussed included motivation to join the trial, time since diagnosis, symptoms, and impacts of EGPA and their degree of ‘bothersomeness’ and ‘disturbance’. The desire to stop or reduce the use of oral glucocorticoids was the most frequently mentioned motivation for, and expectation of, participation in the trial. Comparison of interviews between the 2 time points suggested patients experienced reductions in the number and impact of EGPA-related symptoms and bothersomeness and/or disturbance ratings. Most improved symptoms included difficulty breathing, nasal congestion/discharge, and fatigue, and most improved impacts included ability to exercise, quality/quantity of sleep, and ability to engage in social activities. This study provides insights regarding patients’ perspectives of EGPA and their perceptions and experiences associated with receiving an anti-interleukin-5/receptor therapy. These findings highlight the need for effective treatments that allow patients to reduce their use of oral glucocorticoids and the importance of assessing patient experiences when gauging treatment efficacy in EGPA.

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• The authors reply.

  PubMed · 2025-08-01

  letter
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• Efficacité à 2 ans des traitements anti-IL-5/IL-5R chez les patients atteints de Granulomatose Éosinophilique avec Polyangéite selon les antécédents de sévérité de la maladie

  La Revue de Médecine Interne · 2025-11-25

  articleOpen access

  La Granulomatose Éosinophilique avec Polyangéite (GEPA) est une maladie inflammatoire rare, caractérisée par la présence d’un asthme, d’une hyperéosinophilie et d’une vascularite des vaisseaux de petits à moyens calibres. Les manifestations spécifiques de la GEPA peuvent présenter des degrés de sévérité variables. L’étude MANDARA ( NCT04157348 ) en double insu, sur 52 semaine, a démontré que le benralizumab (1 × 30 mg) était non inférieur au mépolizumab (3 × 100 mg) (administrés par voie sous cutanée toutes les 4 semaines) pour l’atteinte de la rémission chez des patients atteints de GEPA en rechute ou réfractaire. Une analyse post-hoc a montré une efficacité similaire des traitements anti-IL-5/IL-5R indépendamment des antécédents de sévérité de la maladie. Déterminer l’efficacité des thérapies anti-IL-5/IL-5R chez les patients atteints de GEPA, en fonction de la présence ou de l’absence d’antécédents de forme sévère de la maladie, pendant la période en double insu d’un an ainsi que durant la première année de l’extension en ouvert (OLE). Les patients qui ont complétés la période en double insu ont été invités à entrer dans la phase d’extension en ouvert (OLE) au cours de laquelle ils ont soit poursuivi le benralizumab (benra/benra, n = 66), soit sont passés du mepolizumab au benralizumab (mépo/benra, n = 62). Les critères d’évaluations à la semaine 104 comprenaient la rémission (Birmingham Vasculitis Activity Score [BVAS] = 0 et corticothérapie orale [CSO] ≤ 4 mg/jour), la consommation de CSO et la tolérance. Les données des 2 groupes ont été regroupées pour évaluer ces critères selon la présence ou l’absence d’antécédents de GEPA sévère avant l’inclusion dans l’étude. Le groupe « GEPA sévère » incluait des patients ayant présenté par le passé au moins une des atteintes suivantes : cardiomyopathie, glomérulonéphrite, hémorragie alvéolaire ; ou ayant reçu un traitement par cyclophosphamide ou rituximab. Selon les critères d’exclusion, aucun patient n’avait de manifestations sévères de la maladie à l’inclusion dans l’essai. Parmi les 128 patients inclus dans l’étude d’extension en ouvert (OLE), 42 (32,8 %) présentaient des antécédents de forme sévère de GEPA (24 benra/benra, 18 mépo/benra) et 86 (67,2 %) n’avaient pas d’antécédents de forme sévère (42 benra/benra, 44 mépo/benra). Une proportion plus élevée de patients avec des antécédents de maladie sévère recevait un traitement immunosuppresseurs en dehors des CSO depuis le diagnostic de la maladie (GEPA sévère : 32 [76,2 %], GEPA non sévère 45 [52,3 %]) et avait présenté 3 à 5 rechutes (GEPA sévère : 14 [33,3 %], GEPA non sévère : 12 [14,0 %]) dans les 2 ans précédant l’inclusion. La proportion de patient ANCA positif était similaire dans les 2 groupes (GEPA sévère : 12 [28,6 %] ; GEPA non sévère : 23 [26,7 %]). Des taux de rémission ajustés similaires ont été obtenus à la semaine 104, indépendamment des antécédents de gravité de la maladie (GEPA sévère : 74,4 % ; GEPA non sévère : 60,2 % ; différence : 14,28 [intervalle de confiance (IC) 95 % : –2,53 à 31,10], p = 0,0960). Les taux ajustés de rémission obtenue à la semaine 24 et maintenue jusqu’à la semaine 104 étaient également comparables entre les groupes (GEPA sévère : 28,9 % ; GEPA non sévère : 20,9 % ; différence : 7,98 [IC 95 % : –7,52 à 23,47], p = 0,3129). Entre les semaines 101 et 104, une proportion similaire de patients des groupes sévère et non sévère a obtenu une réduction ≥ 50 % de la dose de CSO par rapport à la valeur à l’inclusion (GEPA sévère : 71,9 % ; GEPA non sévère : 67,2 % ; différence : 4,63 [IC 95 % : –12,11 à 21,37], p = 0,5875) et 54,8 % contre 38,4 % ont pu arrêter totalement les CSO (différence : 16,37 [IC 95 % : –1,54 à 34,27], p = 0,0732). Les événements indésirables et événements indésirables graves étaient similaires entre les groupes, quelles que soient les antécédents de sévérité. Les thérapies anti-IL-5/IL-5R ont démontré une efficacité similaire concernant l’obtention de la rémission, l’utilisation de CSO et le profil de tolérance chez des patients atteints de GEPA indépendamment des antécédents de forme sévère de la maladie. Ces données suggèrent un rôle des thérapies anti-IL-5/IL-5R dans la prise en charge des patients atteints de GEPA, y compris chez ceux avec des antécédents de manifestations sévère de la GEPA, en cohérence avec les recommandations de prise en charge EULAR1. Le rôle des anti-IL-5/IL-5R pour la prise en charge des manifestations actives de GEPA sévère requirent néanmoins d’autres études et des données issues d’études en vie réelle seront nécessaires pour valider ces analyses post-hoc préliminaires.

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• Effects of clofutriben, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, on the efficacy and toxicity of prednisolone in patients with polymyalgia rheumatica: a single-blind controlled trial with sequential cohorts

  Annals of the Rheumatic Diseases · 2025-11-13 · 2 citations

  articleOpen access

  OBJECTIVES: Glucocorticoids effectively treat many diseases, but toxicity limits their utility. We aimed to learn whether, by reducing active intracellular glucocorticoid exposures, the 11β-hydroxysteroid dehydrogenase type 1 inhibitor clofutriben could selectively reduce glucocorticoid efficacy but reduce toxicity more strongly. We hypothesised that by increasing the prednisolone dose, it might be possible to restore efficacy back to the original level, thereby improving the benefit-risk profile. METHODS: In sequential cohorts, adults with polymyalgia rheumatica received (single blind) prednisolone 10 mg/d with placebo for 2 weeks, then clofutriben with either prednisolone 10, 15, 20, or 30 mg/d for 2 weeks. RESULTS: Forty-nine and 47 participants completed each trial period with evaluable data. Five who received prednisolone 10 mg/d with clofutriben experienced clinical relapse. No clinical relapses occurred during other treatments. Participants reported more severe symptoms and physical disability when prednisolone 10 mg/d or 15 mg/d, but not 20 mg/d or 30 mg/d, was given with clofutriben. Inflammatory biomarkers followed a similar pattern. Across all prednisolone doses, clofutriben coadministration mitigated glucocorticoid-related adverse effects on biomarkers of bone turnover, lipid metabolism, hypercoagulability, and cardiovascular and adrenal function. CONCLUSIONS: Further trials to assess clofutriben's potential to improve the benefit-risk profile of prednisolone are warranted.

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• Mycophenolate mofetil plus methotrexate versus cyclophosphamide with sequential azathioprine for treatment of Takayasu arteritis

  Annals of the Rheumatic Diseases · 2025-08-22 · 4 citations

  articleOpen access

  OBJECTIVES: Study the efficacy and safety of mycophenolate mofetil (MMF) combined with methotrexate (MTX) compared to cyclophosphamide (CYC) followed by azathioprine (AZA) to treat active Takayasu arteritis (TAK). METHODS: Adults with active TAK were randomised in a 2:1 ratio to receive oral MMF plus MTX or intravenous CYC followed by oral AZA. All subjects also received high-dose oral glucocorticoids with a predefined taper. The primary endpoint was overall response rate at week 52, defined as achieving a complete response (CR) or partial response (PR). Secondary endpoints included rates of CR and PR at weeks 28 and 52. RESULTS: A total of 111 patients with TAK were enrolled: 74 in the MMF+MTX group and 37 in the CYC/AZA group, with comparable baseline demographic and clinical features. The overall response rates at 28 and 52 weeks were 58.1% and 55.4% in the MMF+MTX group, respectively, higher than 32.4% at both time points in the CYC/AZA group (P = .011 and .022). CR and PR rates at 28 and 52 weeks were also higher in the MMF+MTX group. Relapse occurred in 4 patients in the MMF+MTX group and 2 in the CYC/AZA group. One serious adverse event, neutropenia with fever, occurred in 1 patient in the CYC/AZA group. CONCLUSIONS: Treatment of active TAK with MMF+MTX has more favourable efficacy compared to CYC/AZA. These findings provide evidence to use the combination of MTX and MMF, 2 generally well-tolerated and inexpensive therapies, to treat TAK.

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• Clinician views concerning the prevalence and impact of granulomas on the diagnosis, management, and outcomes of ANCA-associated vasculitis

  Lara D. Veeken · 2025-11-02

  articleOpen access

  OBJECTIVES: It is unclear whether clinicians agree which manifestations of ANCA-associated vasculitides (AAV) is associated with necrotizing granulomas or if their presence affects clinical decision-making. METHODS: We surveyed physicians experienced in caring for individuals with AAV, querying: experience with AAV; beliefs concerning how granulomas affect the diagnosis, treatments and outcomes of AAV; beliefs concerning the frequency with which granulomas are found in 36 manifestations of AAV; and degree to which granulomas change choice of induction therapy for specific manifestations of AAV. We analysed responses using descriptive statistics and multivariable linear regression. RESULTS: We received 142 responses from 35 countries. Responses had a median Likert response ≥5 on a seven-point scale (equal to 'partially agree') that granulomatous manifestations respond differently to therapy, increase risk of relapse and increase organ damage. Four of 36 manifestations were believed to be caused by granulomas in a median of ≥75% of cases (on a scale of 0 = never to 100 = always caused by granuloma), 19 in a median of ≤25% of cases, and 13 in intermediate medians. The perceived degree to which granulomas caused manifestations was not associated with changes in therapy to induce remission in severe AAV (P-values 0.26-0.93 across scenarios). CONCLUSIONS: Physicians experienced in vasculitis generally agree on which manifestations of AAV are and are not caused by granulomas and that granulomatous inflammation alters the natural history and treatment of AAV. However, the presence of granulomatous manifestations did not alter treatment choices to induce remission in severe AAV.

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• Discontinuation of Oral Glucocorticoids and Achievement of Remission in Patients With Eosinophilic Granulomatosis With Polyangiitis Treated With Benralizumab or Mepolizumab

  ACR Open Rheumatology · 2025-08-31 · 3 citations

  articleOpen accessSenior authorCorresponding

  OBJECTIVE: In the phase 3 head-to-head MANDARA study (NCT04157348), benralizumab demonstrated noninferiority to mepolizumab in inducing remission (defined as Birmingham Vasculitis Activity Score [BVAS] of 0 and oral glucocorticoid [OGC] dosage ≤4 mg/day at weeks 36 and 48) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This analysis investigated a more stringent definition of remission that included discontinuation of OGCs and being relapse-free. METHODS: Patients aged ≥18 years with documented relapsing or refractory EGPA receiving OGCs at ≥7.5 mg/day with or without immunosuppressive therapy for ≥4 weeks before enrollment were randomized (1:1) to benralizumab at 30 mg or mepolizumab at 300 mg subcutaneously every 4 weeks for 52 weeks. The proportion of patients achieving remission off OGCs, defined as BVAS of 0, OGC dose of 0 mg/day (at weeks 36 and 48) and no relapses during the double-masked period, was assessed. RESULTS: Patients (n = 140) were randomized to benralizumab (n = 70) or mepolizumab (n = 70). The adjusted percentage of patients with remission off OGCs was 23.5% (n = 16) with benralizumab versus 11.1% (n = 8) with mepolizumab (difference 12.47 [95% confidence interval 0.46-24.48], P = 0.042). Of those who achieved remission off OGCs, 100% of benralizumab-treated patients and 98.6% of mepolizumab-treated patients achieved remission within the first 36 weeks of treatment. CONCLUSION: The administration of anti-interleukin-5/receptor (IL-5/R) therapies, benralizumab and mepolizumab, enable discontinuation of OGCs in some patients with EGPA, while avoiding relapses. These findings suggest that adding anti-IL-5/R therapy to standard primary treatment for patients with EGPA may improve response.

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• Chimeric antigen receptor T-cell therapy in patients with coexisting malignancy and autoimmune disease

  Blood · 2025-11-03

  articleOpen access

  Abstract Background: Chimeric antigen receptor (CART) therapies targeting CD19 or BCMA have shown great potential for treating autoimmune diseases (AD) in early-phase trials by depleting autoreactive B cells and plasma cells, resetting immune tolerance. While these findings suggest efficacy, current clinical evidence is limited to small, selected cohorts. We conducted a real-world analysis of patients (pts) with coexisting AD and relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) or multiple myeloma (MM) treated with commercial CART19 or BCMA-CART. Methods: We studied 601 pts with r/r B-NHL or MM treated with commercial CART19 or BCMA-CART from 01/2018 to 12/2024 ( data cutoff: June 2025) at our institution. Antitumor responses were evaluated by Lugano criteria (NHL) and IMWG criteria (MM), and adverse events by ASTCT guidelines. AD was defined as active in the presence of serological markers and need for therapy. AD responses were based on symptom improvement and reduced immunosuppression; flares were defined as new/worsening symptoms or increased treatment need. Serum autoantibody profiling (Chang; Nat Commun. 2021) was performed on paired samples from 90 pts (51 CART19, 39 BCMA-CART) at day 0 and month 3 (M3) post-CART. Results: Overall, 403 (67%) pts had B-NHL and 198 (33%) MM. Median follow-up was 26 months. Forty-nine pts (8.2%) had a history of AD (36 with B-NHL; 13 with MM). ADs included rheumatoid arthritis (RA, n=12), autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (n=9), sarcoidosis (n=9), systemic lupus erythematosus (SLE) or undifferentiated connective tissue disease (n=7), autoimmune thyroid disease (n=4), and inflammatory bowel disease (IBD, n=4). Less common ADs included psoriasis (n=2) and one case each of type 1 diabetes, ankylosing spondylitis, Sjogren's syndrome, uveitis, polymyalgia rheumatica, and autoimmune colitis. Four pts had multiple ADs. AD was more common in females (AD: 57% vs 35%, p<0.01). Within B-NHL and MM cohorts, baseline characteristics (age, histology, CART product, prior lines, transplant history) were similar between AD and non-AD groups.We first evaluated antitumor efficacy and safety of CART19 and BCMA-CART in patients with and without AD. Response rates, progression-free survival, overall survival, and incidence and severity of cytokine release syndrome and neurotoxicity were comparable (p>0.05).We then assessed the impact of CART on AD. Among 49 pts with AD, 2 B-NHL patients (4%)—1 with RA (RA#1) and 1 with SLE (SLE#1)—had active AD at CART19 infusion. Both were symptomatic and on treatment at CART infusion. RA#1 remained in AD remission until death from lymphoma progression 2.5 years post-CART. SLE#1 had a baseline ANA titer of 1:20,000, which decreased to 1:2,500 at M3 post-CART, accompanied by reduced DNA-associated antibodies (anti-histones, KU, P70/80, H2B, H2A/4, H3, H1, nucleolin; median fold change [FC] −70%, range −39% to −84%). In contrast, anti-Smith remained stable (FC −6%) while anti-SSB increased (FC +39%), suggesting selective depletion of pathogenic B-cell clones. SLE#1 experienced SLE relapse 2.3 years post-CART with isolated cutaneous involvement, while in remission of B-NHL.We then evaluated the 47 pts with AD in remission at the time of CART infusion. While 41 (87%) pts maintained AD remission, 6 (13%) pts (3 RA, 1 psoriasis, 1 IBD, and 1 AIHA) experienced AD flares within 3 months post-CART. All resolved with appropriate therapy: corticosteroids (n=2,RA), non-steroidal anti-inflammatory (n=1, RA), topical steroids plus phototherapy (psoriasis), mesalamine (IBD), or red blood cell transfusions (AIHA). To assess the broader impact of CART19 and BCMA-CART on the pt autoreactome (individual-specific autoantibody repertoire; Bodansky; JCI 2024), independently of AD diagnosis, we profiled 90 pts using a bead-based array targeting 52 autoantigens (Chang; Nat Commun. 2021). Both therapies modulated the autoreactome, with BCMA-CART inducing a significantly greater median reduction in autoantibodies (72% vs. 31%, p<0.001), supporting its broader potential in autoantibody-driven diseases. Conclusion: CART confirms durable AD control in real-world pts with coexisting NHL/MM. However, a subset of pts with AD in remission at infusion may experience post-CART AD flares, possibly due to the post-treatment inflammatory state, warranting close monitoring. Further studies are needed to understand flares' pathogenesis and their link with CART activity.

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• Risk Factors for Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Among Patients With Relapse After Induction of Remission With Rituximab

  Arthritis & Rheumatology · 2025-12-19

  articleOpen access

  Objective The objective of the study was to determine risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) after reinduction of remission with rituximab and discontinuation of maintenance therapy. Methods This is a post hoc analysis of the RITAZAREM clinical trial. Patients aged 15 years or older with AAV and a positive test for anti–proteinase‐3 or anti‐myeloperoxidase‐ANCA who achieved remission after reinduction with rituximab and glucocorticoids were randomized at month 4 to receive continued rituximab or azathioprine for a maintenance period up to 24 months, followed by observation until relapse or up to 48 months. Generalized estimating equations logistic regression identified baseline and time‐varying risk factors for relapse by the next visit for the two study phases: maintenance (months 4–24) and off‐treatment (months 24–48). Results Among 170 patients (median [interquartile range] age 59 [48–68] years, disease duration 5 [2–10] years), 99 relapses occurred (46 during maintenance). During maintenance, musculoskeletal involvement (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.1–7.2; P = 0.03) and higher patient global assessment (OR: 1.1, 95% CI: 1.0–1.2; P = 0.04) were associated with relapse. During the off‐treatment phase, presence of CD19 + B cells (OR: 2.5, 95% CI: 1.2–5.1; P = 0.01) and reappearance of ANCA (OR: 3.2, 95% CI: 1.3–7.7; P = 0.01) were each associated with higher relapse risk. Multivariable analysis identified markers of inflammation (changes in platelets, white blood cells, and IgA) associated with relapse. Conclusion Risk factors for relapse in AAV vary by treatment phase. Monitoring markers of inflammation and immune reconstitution may identify patients at risk for relapse, particularly after treatment withdrawal.

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• A glossary of signs and symptoms of giant cell arteritis

  Annals of the Rheumatic Diseases · 2025-07-28

  articleOpen access

  OBJECTIVES: This study seeks to create consensus-based definitions of signs and symptoms of giant cell arteritis (GCA) for use by health care professionals, primarily in research settings. METHODS: Core definitions of signs and symptoms of GCA were extracted from 11 randomised controlled trials of GCA previously reviewed in a systematic literature review conducted in the context of the development of response criteria for GCA. This information was supplemented by definitions from other sources, such as rheumatology textbooks. A 2-round Delphi was performed within an international task force (32 members from 11 countries). The first round aimed to obtain consensus on the descriptive terms defining each sign or symptom, and round 2 rated the importance of these terms. Based on the Delphi study method, preliminary definitions were developed. In 4 online meetings, results of the Delphi were reviewed, and a consensus was achieved on final definitions. RESULTS: Twenty-nine signs and symptoms of GCA were reviewed. Six signs or symptoms of GCA had previously been defined in the literature. A high level of agreement was reached on the definition of 23 signs and symptoms with the following 12 considered characteristic of GCA: headache, temporal artery abnormalities, scalp tenderness, scalp necrosis, jaw claudication, tongue claudication, tongue necrosis, amaurosis fugax, permanent vision loss, fever, limb claudication, and blood pressure inequality. CONCLUSIONS: A glossary of definitions for 23 signs and symptoms of GCA was developed through a consensus process involving international experts.

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Recent grants

• NIH Grant U54RR019497

  NIH · $11.1M · 2009

• NIH Grant K24AR002224

  NIH · $609k · 2007

• NIH Grant P60AR047785

  NIH · $29.4M · 2018

• Adaption and Validation of PROMIS for use in Vasculitis

  NIH · $1.5M · 2012–2019

• NIH Grant RC1AR058303

  NIH · $1.0M · 2012

Frequent coauthors

• Paul A. Monach

  Brigham and Women's Hospital

  424 shared

• Gary S. Hoffman

  422 shared

• Carol A. McAlear

  University of Pennsylvania

  412 shared

• Carol A. Langford

  Cleveland Clinic

  411 shared

• Robert Spiera

  358 shared

• Ulrich Specks

  Mayo Clinic in Arizona

  357 shared

• Raashid Luqmani

  NIHR Oxford Musculoskeletal Biomedical Research Centre

  356 shared

• E. William St. Clair

  347 shared