Early Treatment with Addition of Low Dose Prednisolone to Methotrexate Improves Therapeutic Outcome in Severe Psoriatic Arthritis

Abstract

Psoriatic arthritis (PsA) is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs), the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs) especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week), given for 4 weeks. Addition of prednisolone (10 mg on alternate days) controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week) and prednisolone (2.5 mg on alternate days) every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than ‘steroid rescue’ later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

Introduction

What was known?

Use of systemic steroids as ‘rescue therapy’ in severe psoriatic arthritis

Psoriatic arthritis (PsA), a sero-negative spondyloarthropathy/arthritis, is a common extra-cutaneous manifestation of psoriasis seen in 6-42% of patients with several overlapping subtypes.[1] In up to 70% patients, arthritis symptoms develop years after skin lesions while in 15% of PsA patients the initial presentation is arthritis and psoriasis together.[1,2] Although the pattern of severity of the PsA does not necessarily correlate to that of the skin disease, it is increasingly being perceived to cause progressive joint damage and disability. As with other spondyloarthropathies, musculoskeletal manifestations of PsA also include anthesitis (inflammation at the site of attachment of tendons and ligaments), especially at Achilles tendon and plantar fascia insertions. Akin to inflammatory response seen in psoriasis lesions, activated CD8+ cells expressing HLA-DR molecules and interleukin (IL)-2 receptors are found in plasma and synovium which secrete multiple inflammatory cytokines including IL-1, IL-2, IL-10 and TNF-α leading to proliferation and activation of synovial fibroblasts and increased osteoclast precursors resulting in enhanced osteoclastogenesis and bony erosions.[3,4] While patients with mild symptoms or only a few involved joints may do well with non-steroidal anti-inflammatory drugs (NSAIDs), those with progressive and destructive disease would benefit from an early and more effective treatment to prevent significant permanent joint damage. However, clinical benefits of conventional disease-modifying anti-rheumatic drugs (DMARDs) with broadly immunosuppressive effects are often unpredictable or limited by their side effects. In this communication, we share our experience of treating progressively severe PsA with a combination of low-dose prednisolone and methotrexate.

Case Report

This 18-year-old HIV-negative man presented with progressively increasing low back pain, and painful red swelling and morning stiffness of the left knee, ankle, right shoulder, and multiple interphalangeal (fingers/toes) joints, and psoriasis lesions over trunk, limbs, and scalp (BSA < 20%) for the last 4 months. Nails showed Beau's lines, distal onycholysis, and loss of a few nails. All movements of the involved joints were painful and severely restricted and he was unable to walk without support/wheel chair. Except for bilateral anterior uveitis, systemic examination was normal. He had low hemoglobin (Hb 7.8 g%) and elevated erythrocyte sedimentation rate (ESR 68 mm in the first hour, Westergren method). Blood counts, serum biochemistry, rheumatoid factor, urinalysis, and X-ray chest were normal. X-rays of knees, ankles, elbows, and wrists showed periarticular soft tissue swelling and decreased joint space without significant structural damage. X-ray sacroiliac joints showed reduced joint space and sclerosis, more so of the right joint. Treatment was started with diclofenac sodium (50 mg three times daily), and hematinics and methotrexate (15 mg/week). Uveitis improved after treatment from ophthalmologist with topical atropine sulfate 1% ointment every 8 h initially and then at bed time, and prednisolone acetate 1% ophthalmic drops instilled at 1 h interval and tapered off to three times a day. Addition of indomethacin (25 mg three times/day) a week later too did not benefit and his joint pains/stiffness progressed relentlessly during the next 4 weeks when prednisolone (10 mg on alternate days) was added. Diclofenac sodium could be discontinued within a week as his joint pains and general condition improved significantly. Indomethacin was stopped and the doses were reduced for methotrexate (10 mg/week) and prednisolone (5 mg on alternate days) at 4 weeks. Subsequently, the doses of methotrexate and prednisolone were gradually tapered every 8 weeks. He is asymptomatic, participating in school sports/activities, has occasional skin lesions, uveitis resolved, hemoglobin at 10 g%, no joint deformities, or drug adverse effects during 15 months of follow-up. He is taking prednisolone (2.5 mg on alternate days) along with methotrexate 2.5 mg/week at last visit.

Discussion

PsA has traditionally been viewed as a disease with benign prognosis. However, radiographic evidence indicates that the disease is more progressive and destructive than previously thought. Inflammatory eye involvement too has been observed in one-third PsA patients.[5] About 20% of patients with PsA develop severe disability and nearly 50% will develop erosive arthritis in the first 2 years itself.[2] Our clinical experience too suggests that patients with initial mild PsA often develop severe deforming disease later. Characteristic radiographic features of PsA include reduced joint space (as seen in our patient), joint erosions, periarticular and shaft periostitis, osteolysis, spondylitis, spur formation, and ankylosis varying with its severity.[1] An early and effective intervention is thus imperative before significant permanent damage to a joint occurs. Treatment of psoriatic arthritis with NSAIDs has generally been similar to that of other types of inflammatory arthritis despite concerns that NSAIDs may exacerbate the associated skin disease. PsA unresponsive to NSAIDs is usually managed with DMARDs such as methotrexate, sulfasalazine, gold salts, cyclosporine, or leflunamide. However, potential differences in their efficacy and toxicity need be evaluated before using these drugs. For instance, in a comparative study, the difference in efficacy was not significant for three drugs (methotrexate, sulfasalzine, and parenteral gold) in PsA and rheumatoid arthritis while the PsA patients required treatment for longer period and toxicity was more frequent among them.[6] Further, adverse effects from drug – drug interaction may occur more often when methotrexate is combined with NSAIDs. Also, there is very little data or radiographic evidence that DMARDs have lessened joint pain and inflammation or limited the progression of joint damage in PsA. Clinical and radiographic progression was observed significantly reduced in the groups treated with etanercept, adalimumab, or infliximab with or without adding methotrexate at the baseline level suggesting that biologic response modifiers may have better efficacy without toxicities versus conventional therapies.[1] However, these are prohibitively expensive and patients with mild joint symptoms or only a few involved joints may not need treatment with biologics. Although corticosteroids, systemic or intra-articular, have been used in mutilating PsA for rescue, there are concerns over worsening of skin disease, particularly after withdrawal of relatively short courses, and that the corticosteroids may cause the skin disease to become resistant to other therapies. Other workers too have suggested that the use of corticosteroids is perhaps a risk factor for the development of PsA in a psoriasis patient.[7] Our patient showed no significant improvement in PsA with the NSAIDs given alone or in combination with methotrexate. In fact, it was frustrating for the patient and his family members as he was not getting any relief. His symptoms decreased in the first week itself and he became asymptomatic, even without NSAIDs, as the treatment with low dose prednisolone and methotrexate progressed. Methotrexate combined with betamethasone had cleared the lesions faster and with a longer remission period compared with methotrexate alone in a randomized study.[8] However, this study did not evaluate patients having psoriatic arthritis. With their well-recognized anti-inflammatory, anti-proliferative, and immunosuppressive activities corticosteroids perhaps act at all levels of inflammatory response in synovium/PsA/enthesitis just as in psoriatic lesions and prevent osteoclastogenesis/bony erosions. However, corticosteroids at best be considered as temporizing agents to assist in bringing the inflammation of PsA under control while an alternative therapy, which may have a more gradual onset of action, will provide long lasting control sparing the patients from the potential drug toxicity. We feel that monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in the early stage of the PsA rather than as ‘steroid rescue’ later. This will achieve an early symptomatic relief in PsA, prevent joint damage in the long run, and maintain good functional capacity and quality of life especially when the cost or availability of biologics precludes their use. However, more controlled studies are needed before making any recommendations. The use of systemic corticosteroids as mono-therapy, however, should be discouraged.

What is new?

Early addition of low dose systemic steroids to methotrexate in severe psoriatic arthritis prevents significant joint damage and maintains long-term functional capacity and quality of life.