Janus Kinase Inhibitor Upadacitinib in Elderly-Onset Rheumatoid Arthritis With Hip Osteoarthritis: A Case Report

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by persistent polyarthritis [1], which can progress to joint destruction. Although various factors can contribute to hip joint degeneration, including age-related changes and coexisting osteoarthritis (OA), patients with advanced hip OA can experience further joint deterioration when RA develops, leading to significant impairment in activities of daily living.

Hip involvement in RA is clinically important because the hip is a major weight-bearing joint, and once affected, patients can develop severe pain, decreased mobility, and rapid functional decline, often resulting in the need for total hip arthroplasty, especially in older adults. In addition, it can be challenging to distinguish inflammatory changes caused by RA from degenerative changes due to OA when both conditions coexist in the hip.

While disease-modifying antirheumatic drugs (DMARDs) are commonly used to control RA disease activity, radiologic improvement in joint structure is rarely observed, particularly in weight-bearing joints. Reports of radiologic changes in the hip joint are especially limited [2]. Elderly-onset rheumatoid arthritis (EORA) is defined as RA with disease onset after the age of 60 years and is increasingly encountered in aging societies [3]. In line with this trend, the age of onset of RA is also increasing [4]. Compared with younger-onset RA, EORA has several distinct clinical characteristics, including more frequent involvement of large joints, a greater burden of systemic symptoms at onset, and a higher prevalence of comorbidities [3].

Longitudinal studies have shown more disease activity, radiographic damage, and functional decline in patients with EORA than in those with younger-onset RA [5]. Because older adult patients often have coexisting degenerative musculoskeletal disorders, such as OA, the diagnosis of EORA can be challenging and delayed or confounded by overlapping symptoms and imaging findings [3].

In general, treatment of EORA follows standard RA strategies, and DMARDs are typically introduced promptly after diagnosis, with escalation to biologic or targeted synthetic DMARDs when conventional therapy fails [3]. Upadacitinib (UPA) is an oral, second generation Janus kinase (JAK) inhibitor with selectivity for JAK1 [6]. By inhibiting JAK1-dependent cytokine signaling pathways, UPA modulates inflammatory cascades involved in RA pathogenesis [6]. UPA has been approved for the treatment of moderate to severe active RA, particularly in patients who have an inadequate response or intolerance to methotrexate, and is classified as a targeted synthetic DMARD [6].

We report a rare case in which the administration of UPA, a JAK inhibitor, led to improvement in RA disease activity and resulted in subtle radiologic changes in a hip joint affected by both RA and OA. This report describes the case of a 78-year-old man with end-stage hip OA who developed EORA and demonstrated clinical improvement and subtle radiographic changes in the hip following treatment with UPA.

Case Report

The patient was a 78-year-old man who presented to our hospital with right hip pain. Four years before presentation, he began experiencing right hip pain and received a diagnosis of end-stage hip OA, for which conservative treatment with analgesics was provided. Three years before presentation, he developed polyarthritis and received a diagnosis of EORA. Treatment with corticosteroids and actarit was initiated. However, at presentation, his right hip pain had worsened, prompting referral to our hospital for surgical evaluation.

At initial presentation, the patient reported right hip pain, left knee pain, bilateral shoulder pain, neck pain, bilateral temporomandibular joint pain, and pain in finger joints. On physical examination, tenderness was present in the right hip, left knee, and left fifth metacarpophalangeal joint. Blood tests showed a C-reactive protein (CRP) level of 7.22 mg/dL (reference range, <0.3 mg/dL in our hospital laboratory), a Simplified Disease Activity Index (SDAI) [7] of 22.2, and a Disease Activity Score 28-CRP (DAS28-CRP) [8,9] of 4.4, consistent with high disease activity and poorly controlled RA. Radiographic investigation revealed findings of end-stage coxarthrosis, such as complete loss of the joint space, subchondral sclerosis, and subchondral cysts.

Since the patient’s symptoms were not adequately controlled with corticosteroids and actarit, we discontinued actarit and initiated treatment with iguratimod. Methotrexate was not used, owing to interstitial shadowing seen on chest radiography. Additional therapies, including salazosulfapyridine and tacrolimus, were attempted, but no improvement in disease activity was achieved. At 6 months after presentation, UPA was introduced to suppress disease activity. Following UPA initiation, his disease activity improved markedly. Nine months after initiation of treatment at our hospital, corticosteroids was discontinued, and the patient’s SDAI decreased to 3.0 under UPA monotherapy (Figure 1).

After initiation of UPA, the patient’s DAS28-CRP improved to 1.5, and no tender or swollen joints were observed on physical examination. In addition, the Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire [10], an objective measure of hip-related pain and function, improved from 24 of 84 points at the initial visit to 8 of 84 points, indicating symptomatic improvement.

Radiographic changes were also observed in parallel with clinical improvement. Two months after UPA initiation, the joint space in the right hip began to reappear, and by 6 months, subchondral bone became clearly visible on radiography (Figure 2). Because the pain improved, the patient declined total hip arthroplasty, and conservative follow-up continued.

At 1 year, computed tomography showed a smooth subchondral bone surface (Figure 3), and magnetic resonance imaging revealed only mild bone marrow edema in the femoral head, with minimal synovitis and soft tissue inflammation suggesting well-controlled RA.

Although the patient’s right hip pain improved, gait disturbance persisted. Therefore, total hip arthroplasty was performed to improve the patient’s activities of daily living. Intraoperative findings showed only mild inflammation of the acetabular synovium and surrounding tissues, confirming low RA disease activity. In addition, the femoral head, which was resected during total hip arthroplasty, demonstrated advanced degenerative changes consistent with end-stage coxarthrosis (Figure 4).

Discussion

This case highlights that UPA achieved rapid control of EORA in a patient with end-stage hip OA due to dysplasia of the hip, with concurrent improvement in hip symptoms and subtle radiographic changes. These findings underscore the importance of reassessing hip imaging after tight inflammatory control when OA and RA coexist. Radiographic subchondral bone reappearance in the hip has been reported mainly in younger patients with RA treated with DMARDs or biologics; therefore, such changes observed in a patient with EORA, with end-stage hip OA and under JAK inhibitor therapy, appear exceedingly rare.

To contextualize these findings, we briefly review the clinical overlap between OA and RA in the hip and the challenges in evaluating structural changes in weight-bearing joints. OA is the most common form of arthritis and a leading cause of pain and disability in older adults, and its prevalence is increasing with population ageing and obesity [11]. OA is a heterogeneous disorder influenced by age-related degeneration, biomechanical loading, and local inflammatory pathways [11]. Hip OA can be accelerated by structural abnormalities, such as dysplasia of the hip, which predispose to early degenerative change and progression [11].

RA is a chronic systemic inflammatory disease that causes persistent synovitis and can lead to progressive cartilage and bone damage, resulting in long-term functional disability [12]. Current RA management emphasizes early diagnosis and timely initiation of DMARD-based therapy, with escalation to biologic or targeted synthetic DMARDs in patients with insufficient response to conventional therapy [12].

When OA and RA coexist in major weight-bearing joints such as the hip, clinical evaluation can be challenging because pain and structural deterioration can reflect degenerative and inflammatory mechanisms [11,12]. Radiographs are essential for assessing structural OA severity (joint space narrowing, osteophytes, and subchondral sclerosis), whereas magnetic resonance imaging can support the assessment of inflammatory activity by detecting synovitis and bone marrow edema [11,12]. Management therefore requires an integrated approach, combining optimal control of systemic inflammation with symptomatic OA treatment, and considering total hip arthroplasty when pain and functional limitation persist despite appropriate medical therapy [11,12].

EORA is a distinct clinical subset of RA, often characterized by frequent large-joint involvement, high inflammatory activity at onset, and multiple comorbidities, which can complicate diagnosis and management in older adults [3].

In particular, NSAIDs are frequently contraindicated, and long-term glucocorticoid use increases the risk of adverse events; therefore, prompt optimization of DMARD therapy, including the use of biologic or targeted synthetic agents when indicated, is emphasized in recent reviews of EORA [3].

Although there have been some reports of subchondral bone reappearance in large joints other than the hip in patients with RA, similar findings in the hip joint are rare. Cases of subchondral bone appearance in the hip have been mainly reported in younger patients with RA treated with DMARDs or biologic agents [13]. Furthermore, in patients with advanced Larsen grades, joint destruction can continue even when RA activity is under control [14–16]. Notably, previously published reports describing radiographic structural improvement in an end-stage osteoarthritic hip after targeted antirheumatic therapy are extremely limited. The present case suggests that even in EORA patients with end-stage hip OA due to dysplasia of the hip, treatment with JAK inhibitors, such as UPA, can lead to symptomatic improvement and radiographic evidence of joint improvement.

A more comprehensive understanding of the factors associated with radiographic improvement under JAK inhibitor therapy will require larger, longitudinal studies and detailed imaging analyses.

Conclusions

This case suggests that UPA can achieve rapid disease control in EORA and may be accompanied by changes in hip symptoms and radiographic appearance even in the setting of end-stage hip OA. When OA and EORA coexist in the hip, clinicians should consider repeat imaging after inflammation is tightly suppressed, to better interpret persistent pain and structural findings.